Back to results

Study With AG-013736 Combined With Chemotherapy And Bevacizumab In Patients With Metastatic Colorectal Cancer

Primary Purpose

Colorectal Neoplasms

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

bevacizumab

AG-013726

AG-013736 (axitinib)

About this trial

This is an interventional treatment trial for Colorectal Neoplasms focused on measuring GI neoplasms (phase 1)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

(Phase 1) Patients with any solid/GI tumor who have had no more than 1 previous chemotherapy for greater than 3 months prior to enrollment
(Phase 2) Patients with locally advanced or metastatic colorectal cancer (CRC) previously untreated with any systemic therapy.
Patients treated with adjuvant chemotherapy (with radiation) will be eligible if last treatment was > 12 months prior to enrollment,
Patients must have measurable disease by RECIST and if any history of hypertension, it must be controlled with medication.

Exclusion Criteria:

Prior system therapy for advanced CRC (Ph 2 portion only)
Prior treatment with anti-angiogenesis agent such as bevacizumab or VEGF inhibitors.
Prior irradiation of greater than 25% of bone marrow (whole pelvis = 25%)
Prior radiation, major surgery, or investigational agent within 4 weeks of study entry except palliative radiotherapy to non-target, metastatic lesions. Minor surgeries should be completed > 2 weeks of enrollment and be fully recovered from any procedure.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Arm Label

Arm Description

bevacizumab 5 mg/kg every 2 weeks + FOLFOX

AG-013726 5 mg bid+ bevacizumab 2 mg/kg every 2 weeks + FOLFOX

AG-013736 5 mg bid starting dose + FOLFOX

Outcomes

Primary Outcome Measures

Percentage of Participants With Objective Response: Phase 2

Percentage of participants with objective response (OR) based assessment of confirmed complete response(CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed CR defined as disappearance of all lesions and no appearance of new lesions. Confirmed PR defined as >=30 percent (%) decrease in sum of the longest dimensions (LD) of the target lesions taking as reference the baseline sum LD , without progression of nontarget lesions and no appearance of new lesions. Confirmed responses are those that persist on repeat imaging study >=4 weeks after initial documentation of response.

Secondary Outcome Measures

Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Axitinib: Phase 1

Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). Pharmacokinetic (PK) parameters of axitinib (AG-013736) were combined for Cohorts 1, 2, and 3. AUClast for axitinib in absence of bevacizumab + FOLFOX was estimated from Cycle 1 Day 8 data and in presence of bevacizumab + FOLFOX was estimated from Cycle 2 Day 1 data. Results were normalized to axitinib 5 mg dose.

Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For Axitinib: Phase 1

AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It was obtained from AUC (0 - t) plus AUC (t - ∞). PK parameters of axitinib (AG-013736) were combined for Cohorts 1, 2, and 3. AUC (t - ∞] for axitinib in absence of bevacizumab + FOLFOX was estimated from Cycle 1 Day 8 data and in presence of bevacizumab + FOLFOX was estimated from Cycle 2 Day 1 data. Results were normalized to axitinib 5 mg dose.

Maximum Observed Plasma Concentration (Cmax) For Axitinib: Phase 1

PK parameters of axitinib (AG-013736) were combined for Cohorts 1, 2, and 3.Cmax for axitinib (AG-013736) in absence of bevacizumab + FOLFOX was estimated from Cycle 1 Day 8 data and in presence of bevacizumab + FOLFOX was estimated from Cycle 2 Day 1 data. Results were normalized to axitinib 5 mg dose.

Minimum Observed Plasma Trough Concentration (Cmin) For Axitinib: Phase 1

Apparent Oral Clearance (CL/F) For Axitinib: Phase 1

Clearance (CL) of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed (F). Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. PK parameters of axitinib (AG-013736) were combined for Cohorts 1, 2, and 3. CL/F for axitinib (AG-013736) in absence of bevacizumab + FOLFOX was estimated from Cycle 1 Day 8 data and in presence of bevacizumab + FOLFOX was estimated from Cycle 2 Day 1 data.

Plasma Decay Half-Life (t1/2) For Axitinib: Phase 1

Plasma decay half-life (t1/2) is the time measured for the plasma concentration to decrease by one half. PK parameters of axitinib (AG-013736) were combined for Cohorts 1, 2, and 3. t1/2 for axitinib in absence of bevacizumab + FOLFOX was estimated from Cycle 1 Day 8 data and in presence of bevacizumab + FOLFOX was estimated from Cycle 2 Day 1 data.

Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Oxaliplatin: Phase 1

Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). PK parameters of oxaliplatin, assessed by estimating total platinum in plasma ultrafiltrate, were combined for Cohorts 1, 2, and 3. AUClast for oxaliplatin in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. Results were normalized to Cycle 1 Day 1 oxaliplatin dose.

Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For Oxaliplatin: Phase 1

AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It was obtained from AUC (0 - t) plus AUC (t - ∞). PK parameters of oxaliplatin, assessed by estimating total platinum in plasma ultrafiltrate, were combined for Cohorts 1, 2, and 3. AUC (0 - ∞) for oxaliplatin in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. Results were normalized to Cycle 1 Day 1 oxaliplatin dose.

Maximum Observed Plasma Concentration (Cmax) For Oxaliplatin: Phase 1

PK parameters of oxaliplatin, assessed by estimating total platinum in plasma ultrafiltrate, were combined for Cohorts 1, 2, and 3. Cmax for oxaliplatin in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. Results were normalized to Cycle 1 Day 1 oxaliplatin dose.

Minimum Observed Plasma Trough Concentration (Cmin) For Oxaliplatin: Phase 1

Clearance (CL) For Oxaliplatin: Phase 1

CL is a quantitative measure of the rate at which a drug substance is removed from the body. PK parameters of oxaliplatin, assessed by estimating total platinum in plasma ultrafiltrate, were combined for Cohorts 1, 2, and 3. CL for oxaliplatin in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data.

Plasma Decay Half-Life (t1/2) For Oxaliplatin: Phase 1

Plasma decay half-life (t1/2) is the time measured for the plasma concentration to decrease by one half. PK parameters of oxaliplatin, assessed by estimating total platinum in plasma ultrafiltrate, were combined for Cohorts 1, 2, and 3. t1/2 for oxaliplatin in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data.

Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For 5-Fluorouracil: Phase 1

Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). PK parameters of 5-FU were combined for Cohorts 1, 2, and 3. AUClast for 5-FU in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. Results were normalized to Cycle 1 Day 1 5-FU dose.

Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For 5-Fluorouracil: Phase 1

AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It was obtained from AUC (0 - t) plus AUC (t - ∞). PK parameters of 5-FU were combined for Cohorts 1, 2, and 3. AUC (0 - ∞) for 5-FU in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. Results were normalized to Cycle 1 Day 1 5-FU dose.

Maximum Observed Plasma Concentration (Cmax) For 5-Fluorouracil: Phase 1

PK parameters of 5-FU were combined for Cohorts 1, 2, and 3. Cmax for 5-FU in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. Results were normalized to Cycle 1 Day 1 5-FU dose.

Minimum Observed Plasma Trough Concentration (Cmin) For 5-Fluorouracil: Phase 1

Clearance (CL) For 5-Fluorouracil: Phase 1

CL is a quantitative measure of the rate at which a drug substance is removed from the body. PK parameters of 5-FU were combined for Cohorts 1, 2, and 3. CL for 5-FU in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data.

Plasma Decay Half-Life (t1/2) For 5-Fluorouracil: Phase 1

Plasma decay half-life (t1/2) is the time measured for the plasma concentration to decrease by one half. PK parameters of 5-FU were combined for Cohorts 1, 2, and 3. t1/2 for 5-FU in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data.

Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Irinotecan: Phase 1

Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). AUClast for irinotecan in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. Results were normalized to Cycle 1 Day 1 irinotecan dose.

Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For Irinotecan: Phase 1

AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It was obtained from AUC (0 - t) plus AUC (t - ∞). AUC (0 - ∞) for irinotecan in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. Results were normalized to Cycle 1 Day 1 irinotecan dose.

Maximum Observed Plasma Concentration (Cmax) For Irinotecan: Phase 1

Cmax for irinotecan in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. Results were normalized to Cycle 1 Day 1 irinotecan dose.

Minimum Observed Plasma Trough Concentration (Cmin) For Irinotecan: Phase 1

Clearance (CL) For Irinotecan: Phase 1

CL is a quantitative measure of the rate at which a drug substance is removed from the body. CL for irinotecan in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data.

Plasma Decay Half-Life (t1/2) For Irinotecan: Phase 1

Plasma decay half-life (t1/2) is the time measured for the plasma concentration to decrease by one half. t1/2 for irinotecan in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data.

Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Bevacizumab: Phase 1

Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). PK parameters of bevacizumab were combined for Cohorts 1, 2, and 3. AUClast for bevacizumab in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. The bevacizumab pharmacokinetic parameters were normalized to 1 mg/kg dose.

Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For Bevacizumab: Phase 1

AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It was obtained from AUC (0 - t) plus AUC (t - ∞). PK parameters of bevacizumab were combined for Cohorts 1, 2, and 3. AUC (0 - ∞) for bevacizumab in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. The bevacizumab pharmacokinetic parameters were normalized to 1 mg/kg dose.

Maximum Observed Plasma Concentration (Cmax) For Bevacizumab: Phase 1

PK parameters of bevacizumab were combined for Cohorts 1, 2, and 3. Cmax for bevacizumab in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. The bevacizumab pharmacokinetic parameters were normalized to 1 mg/kg dose.

Minimum Observed Plasma Trough Concentration (Cmin) For Bevacizumab: Phase 1

Clearance (CL) For Bevacizumab: Phase 1

CL is a quantitative measure of the rate at which a drug substance is removed from the body. PK parameters of bevacizumab were combined for Cohorts 1, 2, and 3. CL for bevacizumab in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data.

Plasma Decay Half-Life (t1/2) For Bevacizumab: Phase 1

Plasma decay half-life (t1/2) is the time measured for the plasma concentration to decrease by one half. PK parameters of bevacizumab were combined for Cohorts 1, 2, and 3. t1/2 for bevacizumab in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data.

Duration of Response (DR): Phase 2

Time in days from the first documentation of objective tumor response to objective tumor progression or death due to any cancer. Duration of tumor response was calculated as the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1. DR was calculated for the subgroup of participants with a confirmed objective tumor response. CR: disappearance of all lesions and no appearance of new lesions. PR: >=30% decrease in sum of LD of target lesions taking as reference the baseline sum LD, without progression of nontarget lesions and no appearance of new lesions. Progression: >=20% increase in sum of LD of target lesions taking as references the smallest sum LD recorded since treatment start, unequivocal progression of existing nontarget lesions, or appearance of new lesions, occurrence of pleural effusion/ascites, substantiated by cytologic investigation.

Progression-Free Survival (PFS): Phase 2

Time in days from date of randomization to first documentation of objective tumor progression or death due to any cause. PFS was calculated as first event date minus the date of first dose of study medication plus 1. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from adverse event (AE) data (where the outcome was "Death"). Progression: >=20% increase in sum of LD of target lesions taking as references the smallest sum LD recorded since treatment start, unequivocal progression of existing nontarget lesions, or appearance of new lesions, occurrence of pleural effusion/ascites, substantiated by cytologic investigation.

Time to Treatment Failure (TTF): Phase 2

TTF is defined as the time from the randomization to the date of the first documentation of PD, symptomatic deterioration, death due to any cause, or treatment discontinuation due to adverse event, refusal or other reasons. Progression: >=20% increase in sum of LD of target lesions taking as references the smallest sum LD recorded since treatment start, unequivocal progression of existing nontarget lesions, or appearance of new lesions, occurrence of pleural effusion/ascites, substantiated by cytologic investigation.

Overall Survival (OS): Phase 2

Time in days from randomization date to date of death due to any cause. OS was calculated as the death date minus the date of first dose of study medication plus 1. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death).

Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2

PROs included assessment of symptom severity and interference which were measured using M.D. Anderson Symptom Assessment Inventory-Diarrhea (MDASI-D), 20-item questionnaire which assesses the severity of 14 symptoms over the past 24 hours, as well as symptoms interference with 6 areas of function (e.g., walking, work, mood), when the symptom was "at its worst". Each item is scored from 0 to 10, with '0' indicating that the symptom was either not present or did not interfere with their activities, and '10' indicating that the symptom was "as bad as you can imagine" or "interfered completely" with their life. The 2 subscales, symptom severity score and symptom interference score were average of respective items and ranged from 0 to 10, higher score indicating greater severity or interference of symptoms.

Full Information

NCT ID

NCT00460603

First Posted

April 13, 2007

Last Updated

November 7, 2013

Sponsor

Pfizer

1. Study Identification

Unique Protocol Identification Number

NCT00460603

Brief Title

Study With AG-013736 Combined With Chemotherapy And Bevacizumab In Patients With Metastatic Colorectal Cancer

Official Title

A Randomized Phase 2 Study Of The Anti-Angiogenesis Agent AG-013736 In Combinations With Chemotherapy And Bevacizumab In Patients With Metastatic Colorectal Cancer Preceded By A Phase 1 Portion

Study Type

Interventional

2. Study Status

Record Verification Date

November 2013

Overall Recruitment Status

Completed

Study Start Date

January 2006 (undefined)

Primary Completion Date

April 2012 (Actual)

Study Completion Date

November 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Pfizer

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

To determine the safety and efficacy of AG-013736 in combination with other standard of care medication in patients with first line metastatic colorectal cancer.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Colorectal Neoplasms

Keywords

GI neoplasms (phase 1)

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

187 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Active Comparator

Arm Description

bevacizumab 5 mg/kg every 2 weeks + FOLFOX

Arm Title

Arm Type

Experimental

Arm Description

AG-013726 5 mg bid+ bevacizumab 2 mg/kg every 2 weeks + FOLFOX

Arm Title

Arm Type

Experimental

Arm Description

AG-013736 5 mg bid starting dose + FOLFOX

Intervention Type

Drug

Intervention Name(s)

bevacizumab

Intervention Description

bevacizumab 5 mg/kg every 2 weeks

Intervention Type

Drug

Intervention Name(s)

AG-013726

Intervention Description

AG-013726 5 mg bid every 2 weeks

Intervention Type

Drug

Intervention Name(s)

AG-013736 (axitinib)

Intervention Description

AG-013736 5 mg bid starting dose

Primary Outcome Measure Information:

Title

Percentage of Participants With Objective Response: Phase 2

Description

Time Frame

Baseline (Phase 2) until disease progression, assessed every 6 weeks up to Week 148 (Phase 2) or follow-up (every 6 weeks after last dose of study drug until progression or start of alternate therapy)

Secondary Outcome Measure Information:

Title

Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Axitinib: Phase 1

Description

Time Frame

Predose, 1, 2, 2.5, 4, 6 and 8 hours postdose on Cycle 1 Day 8, Cycle 2 Day 1

Title

Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For Axitinib: Phase 1

Description

Time Frame

Predose, 1, 2, 2.5, 4, 6, 8 hours postdose on Cycle 1 Day 8, Cycle 2 Day 1

Title

Maximum Observed Plasma Concentration (Cmax) For Axitinib: Phase 1

Description

Time Frame

Predose, 1, 2, 2.5, 4, 6, 8 hours postdose on Cycle 1 Day 8, Cycle 2 Day 1

Title

Minimum Observed Plasma Trough Concentration (Cmin) For Axitinib: Phase 1

Time Frame

Predose, 1, 2, 2.5, 4, 6, 8 hours postdose on Cycle 1 Day 8, Cycle 2 Day 1

Title

Apparent Oral Clearance (CL/F) For Axitinib: Phase 1

Description

Time Frame

Predose, 1, 2, 2.5, 4, 6, 8 hours postdose on Cycle 1 Day 8, Cycle 2 Day 1

Title

Plasma Decay Half-Life (t1/2) For Axitinib: Phase 1

Description

Time Frame

Predose, 1, 2, 2.5, 4, 6, 8 hours postdose on Cycle 1 Day 8, Cycle 2 Day 1

Title

Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Oxaliplatin: Phase 1

Description

Time Frame

Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1

Title

Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For Oxaliplatin: Phase 1

Description

AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It was obtained from AUC (0 - t) plus AUC (t - ∞). PK parameters of oxaliplatin, assessed by estimating total platinum in plasma ultrafiltrate, were combined for Cohorts 1, 2, and 3. AUC (0 - ∞) for oxaliplatin in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. Results were normalized to Cycle 1 Day 1 oxaliplatin dose.

Time Frame

Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1

Title

Maximum Observed Plasma Concentration (Cmax) For Oxaliplatin: Phase 1

Description

Time Frame

Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1

Title

Minimum Observed Plasma Trough Concentration (Cmin) For Oxaliplatin: Phase 1

Time Frame

Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1

Title

Clearance (CL) For Oxaliplatin: Phase 1

Description

Time Frame

Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1

Title

Plasma Decay Half-Life (t1/2) For Oxaliplatin: Phase 1

Description

Time Frame

Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1

Title

Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For 5-Fluorouracil: Phase 1

Description

Time Frame

Pre-5-FU bolus, 5 min (post-5-FU bolus), 0.25, 0.5, 0.75, 2, 4, 6, 22, 34-46 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1

Title

Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For 5-Fluorouracil: Phase 1

Description

AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It was obtained from AUC (0 - t) plus AUC (t - ∞). PK parameters of 5-FU were combined for Cohorts 1, 2, and 3. AUC (0 - ∞) for 5-FU in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. Results were normalized to Cycle 1 Day 1 5-FU dose.

Time Frame

Pre-5-FU bolus, 5 min (post-5-FU bolus), 0.25, 0.5, 0.75, 2, 4, 6, 22, 34-46 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1

Title

Maximum Observed Plasma Concentration (Cmax) For 5-Fluorouracil: Phase 1

Description

Time Frame

Pre-5-FU bolus, 5 min (post-5-FU bolus), 0.25, 0.5, 0.75, 2, 4, 6, 22, 34-46 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1

Title

Minimum Observed Plasma Trough Concentration (Cmin) For 5-Fluorouracil: Phase 1

Time Frame

Pre-5-FU bolus, 5 min (post-5-FU bolus), 0.25, 0.5, 0.75, 2, 4, 6, 22, 34-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1

Title

Clearance (CL) For 5-Fluorouracil: Phase 1

Description

Time Frame

Pre-5-FU bolus, 5 min (post-5-FU bolus), 0.25, 0.5, 0.75, 2, 4, 6, 22, 34-46 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1

Title

Plasma Decay Half-Life (t1/2) For 5-Fluorouracil: Phase 1

Description

Time Frame

Pre-5-FU bolus, 5 min (post-5-FU bolus), 0.25, 0.5, 0.75, 2, 4, 6, 22, 34-46 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1

Title

Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Irinotecan: Phase 1

Description

Time Frame

Predose, 1, 2, 2.5, 4, 6, 8, 24 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1

Title

Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For Irinotecan: Phase 1

Description

AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It was obtained from AUC (0 - t) plus AUC (t - ∞). AUC (0 - ∞) for irinotecan in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. Results were normalized to Cycle 1 Day 1 irinotecan dose.

Time Frame

Predose, 1, 2, 2.5, 4, 6, 8, 24 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1

Title

Maximum Observed Plasma Concentration (Cmax) For Irinotecan: Phase 1

Description

Time Frame

Predose, 1, 2, 2.5, 4, 6, 8, 24 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1

Title

Minimum Observed Plasma Trough Concentration (Cmin) For Irinotecan: Phase 1

Time Frame

Predose, 1, 2, 2.5, 4, 6, 8, 24 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1

Title

Clearance (CL) For Irinotecan: Phase 1

Description

Time Frame

Predose, 1, 2, 2.5, 4, 6, 8, 24 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1

Title

Plasma Decay Half-Life (t1/2) For Irinotecan: Phase 1

Description

Time Frame

Predose, 1, 2, 2.5, 4, 6, 8, 24 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1

Title

Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Bevacizumab: Phase 1

Description

Time Frame

Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1

Title

Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For Bevacizumab: Phase 1

Description

AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It was obtained from AUC (0 - t) plus AUC (t - ∞). PK parameters of bevacizumab were combined for Cohorts 1, 2, and 3. AUC (0 - ∞) for bevacizumab in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. The bevacizumab pharmacokinetic parameters were normalized to 1 mg/kg dose.

Time Frame

Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1

Title

Maximum Observed Plasma Concentration (Cmax) For Bevacizumab: Phase 1

Description

Time Frame

Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1

Title

Minimum Observed Plasma Trough Concentration (Cmin) For Bevacizumab: Phase 1

Time Frame

Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1

Title

Clearance (CL) For Bevacizumab: Phase 1

Description

Time Frame

Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1

Title

Plasma Decay Half-Life (t1/2) For Bevacizumab: Phase 1

Description

Time Frame

Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1

Title

Duration of Response (DR): Phase 2

Description

Time Frame

Title

Progression-Free Survival (PFS): Phase 2

Description

Time Frame

Title

Time to Treatment Failure (TTF): Phase 2

Description

Time Frame

Title

Overall Survival (OS): Phase 2

Description

Time Frame

Every 3 months after discontinuation of study treatment until death due to any cause or 1 year after randomization of the last participant

Title

Description

Time Frame

Cycle 1 Day 1 (baseline), every 2 weeks for the first 2 months (Cycle 2 Day 1 [C2D1], Cycle 3 Day 1, and Cycle 4 Day 1) then monthly thereafter starting Cycle 6 Day 1, and 28 days after the last dose

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: (Phase 1) Patients with any solid/GI tumor who have had no more than 1 previous chemotherapy for greater than 3 months prior to enrollment (Phase 2) Patients with locally advanced or metastatic colorectal cancer (CRC) previously untreated with any systemic therapy. Patients treated with adjuvant chemotherapy (with radiation) will be eligible if last treatment was > 12 months prior to enrollment, Patients must have measurable disease by RECIST and if any history of hypertension, it must be controlled with medication. Exclusion Criteria: Prior system therapy for advanced CRC (Ph 2 portion only) Prior treatment with anti-angiogenesis agent such as bevacizumab or VEGF inhibitors. Prior irradiation of greater than 25% of bone marrow (whole pelvis = 25%) Prior radiation, major surgery, or investigational agent within 4 weeks of study entry except palliative radiotherapy to non-target, metastatic lesions. Minor surgeries should be completed > 2 weeks of enrollment and be fully recovered from any procedure.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Pfizer CT.gov Call Center

Organizational Affiliation

Pfizer

Official's Role

Study Director

Facility Information:

Facility Name

Pfizer Investigational Site

City

Daphne

State/Province

Alabama

ZIP/Postal Code

36526

Country

United States

Facility Name

Pfizer Investigational Site

City

Huntsville

State/Province

Alabama

ZIP/Postal Code

35801

Country

United States

Facility Name

Pfizer Investigational Site

City

Huntsville

State/Province

Alabama

ZIP/Postal Code

35805

Country

United States

Facility Name

Pfizer Investigational Site

City

Mobile

State/Province

Alabama

ZIP/Postal Code

36608

Country

United States

Facility Name

Pfizer Investigational Site

City

Antioch

State/Province

California

ZIP/Postal Code

94531

Country

United States

Facility Name

Pfizer Investigational Site

City

Colton

State/Province

California

ZIP/Postal Code

92324

Country

United States

Facility Name

Pfizer Investigational Site

City

Corona

State/Province

California

ZIP/Postal Code

92879

Country

United States

Facility Name

Pfizer Investigational Site

City

Gilroy

State/Province

California

ZIP/Postal Code

95020

Country

United States

Facility Name

Pfizer Investigational Site

City

Glendora

State/Province

California

ZIP/Postal Code

91741

Country

United States

Facility Name

Pfizer Investigational Site

City

La Jolla

State/Province

California

ZIP/Postal Code

92037

Country

United States

Facility Name

Pfizer Investigational Site

City

La Jolla

State/Province

California

ZIP/Postal Code

92093

Country

United States

Facility Name

Pfizer Investigational Site

City

LaJolla

State/Province

California

ZIP/Postal Code

92093

Country

United States

Facility Name

Pfizer Investigational Site

City

Pasadena

State/Province

California

ZIP/Postal Code

91105

Country

United States

Facility Name

Pfizer Investigational Site

City

Pleasant Hill

State/Province

California

ZIP/Postal Code

94523

Country

United States

Facility Name

Pfizer Investigational Site

City

Pomona

State/Province

California

ZIP/Postal Code

91767

Country

United States

Facility Name

Pfizer Investigational Site

City

Rancho Cucamonga

State/Province

California

ZIP/Postal Code

91730

Country

United States

Facility Name

Pfizer Investigational Site

City

Rancho Mirage

State/Province

California

ZIP/Postal Code

92270

Country

United States

Facility Name

Pfizer Investigational Site

City

Redlands

State/Province

California

ZIP/Postal Code

92374

Country

United States

Facility Name

Pfizer Investigational Site

City

San Diego

State/Province

California

ZIP/Postal Code

92103

Country

United States

Facility Name

Pfizer Investigational Site

City

San Diego

State/Province

California

ZIP/Postal Code

92121

Country

United States

Facility Name

Pfizer Investigational Site

City

San Leandro

State/Province

California

ZIP/Postal Code

94578

Country

United States

Facility Name

Pfizer Investigational Site

City

West Covina

State/Province

California

ZIP/Postal Code

91790

Country

United States

Facility Name

Pfizer Investigational Site

City

Auroa

State/Province

Colorado

ZIP/Postal Code

80012

Country

United States

Facility Name

Pfizer Investigational Site

City

Boulder

State/Province

Colorado

ZIP/Postal Code

80303

Country

United States

Facility Name

Pfizer Investigational Site

City

Colorado Springs

State/Province

Colorado

ZIP/Postal Code

80909

Country

United States

Facility Name

Pfizer Investigational Site

City

Denver

State/Province

Colorado

ZIP/Postal Code

80218

Country

United States

Facility Name

Pfizer Investigational Site

City

Denver

State/Province

Colorado

ZIP/Postal Code

80220

Country

United States

Facility Name

Pfizer Investigational Site

City

Lakewood

State/Province

Colorado

ZIP/Postal Code

80228

Country

United States

Facility Name

Pfizer Investigational Site

City

Littleton

State/Province

Colorado

ZIP/Postal Code

80120-4413

Country

United States

Facility Name

Pfizer Investigational Site

City

Lone Tree

State/Province

Colorado

ZIP/Postal Code

80124

Country

United States

Facility Name

Pfizer Investigational Site

City

Longmont

State/Province

Colorado

ZIP/Postal Code

80501

Country

United States

Facility Name

Pfizer Investigational Site

City

Parker

State/Province

Colorado

ZIP/Postal Code

80138

Country

United States

Facility Name

Pfizer Investigational Site

City

Thornton

State/Province

Colorado

ZIP/Postal Code

80260

Country

United States

Facility Name

Pfizer Investigational Site

City

Ocala

State/Province

Florida

ZIP/Postal Code

34471

Country

United States

Facility Name

Pfizer Investigational Site

City

Stuart

State/Province

Florida

ZIP/Postal Code

34994

Country

United States

Facility Name

Pfizer Investigational Site

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30318

Country

United States

Facility Name

Pfizer Investigational Site

City

Beech Grove

State/Province

Indiana

ZIP/Postal Code

46107

Country

United States

Facility Name

Pfizer Investigational Site

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46237

Country

United States

Facility Name

Pfizer Investigational Site

City

Jeffersonville

State/Province

Indiana

ZIP/Postal Code

47130

Country

United States

Facility Name

Pfizer Investigational Site

City

Muncie

State/Province

Indiana

ZIP/Postal Code

47303

Country

United States

Facility Name

Pfizer Investigational Site

City

Kansas City

State/Province

Kansas

ZIP/Postal Code

66112

Country

United States

Facility Name

Pfizer Investigational Site

City

Overland Park

State/Province

Kansas

ZIP/Postal Code

66210

Country

United States

Facility Name

Pfizer Investigational Site

City

Louisville

State/Province

Kentucky

ZIP/Postal Code

40202

Country

United States

Facility Name

Pfizer Investigational Site

City

Louisville

State/Province

Kentucky

ZIP/Postal Code

40207

Country

United States

Facility Name

Pfizer Investigational Site

City

Louisville

State/Province

Kentucky

ZIP/Postal Code

40217

Country

United States

Facility Name

Pfizer Investigational Site

City

Louisville

State/Province

Kentucky

ZIP/Postal Code

40241

Country

United States

Facility Name

Pfizer Investigational Site

City

Shelbyville

State/Province

Kentucky

ZIP/Postal Code

40065

Country

United States

Facility Name

Pfizer Investigational Site

City

Baton Rouge

State/Province

Louisiana

ZIP/Postal Code

70809

Country

United States

Facility Name

Pfizer Investigational Site

City

Brownstone

State/Province

Michigan

ZIP/Postal Code

48183

Country

United States

Facility Name

Pfizer Investigational Site

City

Dearborn

State/Province

Michigan

ZIP/Postal Code

48126

Country

United States

Facility Name

Pfizer Investigational Site

City

Detroit

State/Province

Michigan

ZIP/Postal Code

48202

Country

United States

Facility Name

Pfizer Investigational Site

City

West Bloomfield

State/Province

Michigan

ZIP/Postal Code

48322

Country

United States

Facility Name

Pfizer Investigational Site

City

Kansas City

State/Province

Missouri

ZIP/Postal Code

64111

Country

United States

Facility Name

Pfizer Investigational Site

City

Kansas City

State/Province

Missouri

ZIP/Postal Code

64131

Country

United States

Facility Name

Pfizer Investigational Site

City

Kansas City

State/Province

Missouri

ZIP/Postal Code

64154

Country

United States

Facility Name

Pfizer Investigational Site

City

Lee's Summit

State/Province

Missouri

ZIP/Postal Code

64064

Country

United States

Facility Name

Pfizer Investigational Site

City

St. Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

Facility Name

Pfizer Investigational Site

City

Grand Island

State/Province

Nebraska

ZIP/Postal Code

68803

Country

United States

Facility Name

Pfizer Investigational Site

City

Las Vegas

State/Province

Nevada

ZIP/Postal Code

89135

Country

United States

Facility Name

Pfizer Investigational Site

City

Summit

State/Province

New Jersey

ZIP/Postal Code

07902

Country

United States

Facility Name

Pfizer Investigational Site

City

Albany

State/Province

New York

ZIP/Postal Code

12206

Country

United States

Facility Name

Pfizer Investigational Site

City

Albany

State/Province

New York

ZIP/Postal Code

12208

Country

United States

Facility Name

Pfizer Investigational Site

City

Amsterdam

State/Province

New York

ZIP/Postal Code

12010

Country

United States

Facility Name

Pfizer Investigational Site

City

Hudson

State/Province

New York

ZIP/Postal Code

12534

Country

United States

Facility Name

Pfizer Investigational Site

City

Latham

State/Province

New York

ZIP/Postal Code

12110-0610

Country

United States

Facility Name

Pfizer Investigational Site

City

Rexford

State/Province

New York

ZIP/Postal Code

12148

Country

United States

Facility Name

Pfizer Investigational Site

City

Troy

State/Province

New York

ZIP/Postal Code

12180

Country

United States

Facility Name

Pfizer Investigational Site

City

Kernersville

State/Province

North Carolina

ZIP/Postal Code

27284

Country

United States

Facility Name

Pfizer Investigational Site

City

Lexington

State/Province

North Carolina

ZIP/Postal Code

27295

Country

United States

Facility Name

Pfizer Investigational Site

City

Mount Airy

State/Province

North Carolina

ZIP/Postal Code

27030

Country

United States

Facility Name

Pfizer Investigational Site

City

North Wilkesboro

State/Province

North Carolina

ZIP/Postal Code

28659

Country

United States

Facility Name

Pfizer Investigational Site

City

Pollocksville

State/Province

North Carolina

ZIP/Postal Code

28573

Country

United States

Facility Name

Pfizer Investigational Site

City

Winston Salem

State/Province

North Carolina

ZIP/Postal Code

27103

Country

United States

Facility Name

Pfizer Investigational Site

City

Oregon City

State/Province

Oregon

ZIP/Postal Code

97045

Country

United States

Facility Name

Pfizer Investigational Site

City

Portland

State/Province

Oregon

ZIP/Postal Code

97213

Country

United States

Facility Name

Pfizer Investigational Site

City

Portland

State/Province

Oregon

ZIP/Postal Code

97225

Country

United States

Facility Name

Pfizer Investigational Site

City

Portland

State/Province

Oregon

ZIP/Postal Code

97227

Country

United States

Facility Name

Pfizer Investigational Site

City

Tualatin

State/Province

Oregon

ZIP/Postal Code

97062

Country

United States

Facility Name

Pfizer Investigational Site

City

West Reading

State/Province

Pennsylvania

ZIP/Postal Code

19611

Country

United States

Facility Name

Pfizer Investigational Site

City

Charleston

State/Province

South Carolina

ZIP/Postal Code

29406

Country

United States

Facility Name

Pfizer Investigational Site

City

Easley

State/Province

South Carolina

ZIP/Postal Code

29640

Country

United States

Facility Name

Pfizer Investigational Site

City

Greenville

State/Province

South Carolina

ZIP/Postal Code

29605

Country

United States

Facility Name

Pfizer Investigational Site

City

Greenville

State/Province

South Carolina

ZIP/Postal Code

29615

Country

United States

Facility Name

Pfizer Investigational Site

City

Seneca

State/Province

South Carolina

ZIP/Postal Code

29672

Country

United States

Facility Name

Pfizer Investigational Site

City

Spartanburg

State/Province

South Carolina

ZIP/Postal Code

29307

Country

United States

Facility Name

Pfizer Investigational Site

City

Chattanooga

State/Province

Tennessee

ZIP/Postal Code

37403

Country

United States

Facility Name

Pfizer Investigational Site

City

Franklin

State/Province

Tennessee

ZIP/Postal Code

37067

Country

United States

Facility Name

Pfizer Investigational Site

City

Gallatin

State/Province

Tennessee

ZIP/Postal Code

37066

Country

United States

Facility Name

Pfizer Investigational Site

City

Hermitage

State/Province

Tennessee

ZIP/Postal Code

37076

Country

United States

Facility Name

Pfizer Investigational Site

City

Lebanon

State/Province

Tennessee

ZIP/Postal Code

37087

Country

United States

Facility Name

Pfizer Investigational Site

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37203

Country

United States

Facility Name

Pfizer Investigational Site

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37205

Country

United States

Facility Name

Pfizer Investigational Site

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37207

Country

United States

Facility Name

Pfizer Investigational Site

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37211

Country

United States

Facility Name

Pfizer Investigational Site

City

Smyrna

State/Province

Tennessee

ZIP/Postal Code

37167

Country

United States

Facility Name

Pfizer Investigational Site

City

Dallas

State/Province

Texas

ZIP/Postal Code

75235

Country

United States

Facility Name

Pfizer Investigational Site

City

Dallas

State/Province

Texas

ZIP/Postal Code

75237

Country

United States

Facility Name

Pfizer Investigational Site

City

Dallas

State/Province

Texas

ZIP/Postal Code

75246

Country

United States

Facility Name

Pfizer Investigational Site

City

Dallas

State/Province

Texas

ZIP/Postal Code

75390

Country

United States

Facility Name

Pfizer Investigational Site

City

Fort Worth

State/Province

Texas

ZIP/Postal Code

76177

Country

United States

Facility Name

Pfizer Investigational Site

City

Houston

State/Province

Texas

ZIP/Postal Code

77090

Country

United States

Facility Name

Pfizer Investigational Site

City

Tyler

State/Province

Texas

ZIP/Postal Code

75702

Country

United States

Facility Name

Pfizer Investigational Site

City

Ogden

State/Province

Utah

ZIP/Postal Code

84403-3274

Country

United States

Facility Name

Pfizer Investigational Site

City

Everett

State/Province

Washington

ZIP/Postal Code

98201

Country

United States

Facility Name

Pfizer Investigational Site

City

Kennewick

State/Province

Washington

ZIP/Postal Code

99336

Country

United States

Facility Name

Pfizer Investigational Site

City

Vancouver

State/Province

Washington

ZIP/Postal Code

98684

Country

United States

Facility Name

Pfizer Investigational Site

City

Vancouver

State/Province

Washington

ZIP/Postal Code

98686

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

24423921

Citation

Hoh CK, Burris HA 3rd, Bendell JC, Tarazi J, Rosbrook B, Kim S, Infante JR, Reid TR. Intermittent dosing of axitinib combined with chemotherapy is supported by (18)FLT-PET in gastrointestinal tumours. Br J Cancer. 2014 Feb 18;110(4):875-81. doi: 10.1038/bjc.2013.806. Epub 2014 Jan 14.

Results Reference

derived

PubMed Identifier

23605883

Citation

Infante JR, Reid TR, Cohn AL, Edenfield WJ, Cescon TP, Hamm JT, Malik IA, Rado TA, McGee PJ, Richards DA, Tarazi J, Rosbrook B, Kim S, Cartwright TH. Axitinib and/or bevacizumab with modified FOLFOX-6 as first-line therapy for metastatic colorectal cancer: a randomized phase 2 study. Cancer. 2013 Jul 15;119(14):2555-63. doi: 10.1002/cncr.28112. Epub 2013 Apr 19.

Results Reference

derived

Links:

URL

https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=A4061020&StudyName=Study%20With%20AG-013736%20Combined%20With%20Chemotherapy%20And%20Bevacizumab%20In%20Patients%20With%20Metastatic%20Colorectal%20Cancer

Description

To obtain contact information for a study center near you, click here.

Learn more about this trial

Study With AG-013736 Combined With Chemotherapy And Bevacizumab In Patients With Metastatic Colorectal Cancer

We'll reach out to this number within 24 hrs

Study With AG-013736 Combined With Chemotherapy And Bevacizumab In Patients With Metastatic Colorectal Cancer

Colorectal Neoplasms

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial