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Docetaxel, Cisplatin, Irinotecan and Bevacizumab (TPCA) in Metastatic Esophageal and Gastric Cancer

Primary Purpose

Esophageal Cancer, Stomach Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Bevacizumab
Docetaxel
Cisplatin
Irinotecan
Sponsored by
Dana-Farber Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Esophageal Cancer focused on measuring TPCA, Taxotere, Platinum, Avastin, Camptosar, gastric cancer

Eligibility Criteria

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

Inclusion Criteria:

  • Histologically confirmed, unresectable esophageal or gastric carcinoma (carcinoma=adenocarcinoma or squamous cell carcinoma)
  • Measurable disease greater than or equal to 1 cm (longest diameter) by spiral computed tomography (CT) scan or 2 cm or greater by other radiographic technique
  • Lesions must be measurable in at least one dimension
  • Bone lesions, ascites, and effusions are not measurable
  • 18 years of age or older
  • ECOG performance status 0 or 1
  • Life expectancy of at least 12 weeks
  • Adequate bone marrow function
  • Adequate renal function
  • Adequate liver function

Exclusion Criteria:

  • Prior chemotherapy (except as part of pre- or post-operative therapy, completed more than 1 year prior to start day of this protocol)
  • History of severe hypersensitivity to bevacizumab, docetaxel, cisplatin, irinotecan, or drugs formulated with polysorbate 80
  • Current, recent (within 4 weeks) or planned participation in an experimental drug study
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, or anticipation of need for major surgical procedure during the course of the study
  • Minor surgical procedures, such as fine needle aspirations, port-a-cath placement, or core biopsies within 7 days prior to Day 0 of study
  • Myocardial infarction or stroke in past 6 months
  • Blood pressure of > 150/100 mmHg
  • Unstable angina
  • New York Heart Association (NYHA) grade II or greater congestive heart failure
  • Clinically significant peripheral vascular disease
  • Persistent bleeding from primary tumor, while off anticoagulants, requiring repeated transfusions
  • Evidence of bleeding diathesis or coagulopathy
  • Uncontrolled serious medical or psychiatric illness
  • Uncontrolled diarrhea
  • Peripheral neuropathy > grade 1
  • Clinically apparent central nervous system metastases or carcinomatous meningitis
  • Other active malignancy other than non-melanoma skin cancer or in situ cervical carcinoma.
  • Urine protein: creatinine ratio of 1.0 or greater at screening
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 1
  • Serious non-healing wound, ulcer, or bone fracture
  • Pregnant or breast-feeding

Sites / Locations

  • Massachusetts General Hospital
  • Beth Israel Deaconess Medical Center
  • Dana-Farber Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Docetaxel, Cisplatin, Irinotecan and Bevacizumab (TPCA)

Arm Description

Patients received bevacizumab 10 mg/kg IV on day 1 every 3 weeks while on study. Additionally, they received docetaxel 30 mg/m2 IV over 30 minutes, followed by cisplatin 25 mg/m2 IV over 30 minutes, followed by irinotecan 50 mg/m2 IV over 30 minutes on days 1 and 8 of each 3-week cycle until disease progression or unacceptable toxicity. Dose reductions were not permitted for bevacizumab although treatment could be held up to 2 months. If bevacizumab was discontinued, treatment with other agents could continue. When docetaxel, cisplatin, or irinotecan was held on day 1 of a cycle, all agents were held.

Outcomes

Primary Outcome Measures

10-month Progression-Free Survival Rate
10-month progression-free survival rate is the probability of patients remaining alive and progression-free at 10-months from study entry estimated using Kaplan-Meier methods. Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.

Secondary Outcome Measures

Best Response
Best response on treatment was based on RECIST 1.0 criteria: Complete Response (CR) is complete disappearance of all target lesions; Partial Response (PR) is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. Both require confirmation no fewer than 4 weeks apart. CR/PR assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions. Progressive disease (PD) is at least a 20% increase in the sum of longest diameter of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions. Stable disease is defined as any condition not meeting above criteria.
Overall Survival
Overall survival is defined as the time from study entry to death or date last known alive and estimate using Kaplan-Meier (KM) methods.
Progression-Free Survival
Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) requiring removal from the study or death. Patients alive and progression-free at last follow-up are censored. Per RECIST 1.0 criteria: progressive disease is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.

Full Information

First Posted
October 31, 2006
Last Updated
July 5, 2017
Sponsor
Dana-Farber Cancer Institute
Collaborators
Brigham and Women's Hospital, Massachusetts General Hospital, Genentech, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00394433
Brief Title
Docetaxel, Cisplatin, Irinotecan and Bevacizumab (TPCA) in Metastatic Esophageal and Gastric Cancer
Official Title
A Phase II Trial of Docetaxel, Cisplatin, Irinotecan and Bevacizumab (TPCA) in Metastatic Esophageal and Gastric Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
July 2017
Overall Recruitment Status
Completed
Study Start Date
September 2006 (undefined)
Primary Completion Date
November 2008 (Actual)
Study Completion Date
October 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Dana-Farber Cancer Institute
Collaborators
Brigham and Women's Hospital, Massachusetts General Hospital, Genentech, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this research study is to determine if the combination of docetaxel, cisplatin, irinotecan and bevacizumab will help shrink metastatic esophageal or gastric cancer and how the cancer responds to this combination. Bevacizumab is a new drug that is believed to stop the formation of new blood vessels that carry nutrients to tumors. Bevacizumab is approved for use in metastatic colon and rectal cancer. Docetaxel, cisplatin and irinotecan are traditional chemotherapy agents that have been tested together in another clinical trial for esophageal and gastric cancer. It is hoped that adding bevacizumab to this regimen will make the treatment more effective.
Detailed Description
OBJECTIVES: Primary To determine the 10-month progression-free survival rate for the combination of TPC and Bevacizumab in patients with metastatic esophageal or gastric cancer Secondary To determine the response rate (RECIST) and median duration of response To determine overall survival To determine toxicity Exploratory To explore if 7/7 and 7/6 UGT1A1 polymorphisms correlate with grade III/IV irinotecan-related diarrhea and neutropenia when irinotecan is given at relatively low dose to patients with esophageal and gastric cancer To correlate expression of tumoral and serum VEGF with response and survival To correlate TGF alpha levels and tumor microvessel density with clinical activity To examine circulating endothelial cells (CECs) as surrogate markers of antitumor activity of bevacizumab DESIGN This trial will use a single stage design to differentiate a >/= 50% rate of 10-month progression-free survival from a </= 30% rate. The proposed regimen would be promising if at least 15 of 35 patients were alive and progression-free at 10 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Esophageal Cancer, Stomach Cancer
Keywords
TPCA, Taxotere, Platinum, Avastin, Camptosar, gastric cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
38 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Docetaxel, Cisplatin, Irinotecan and Bevacizumab (TPCA)
Arm Type
Experimental
Arm Description
Patients received bevacizumab 10 mg/kg IV on day 1 every 3 weeks while on study. Additionally, they received docetaxel 30 mg/m2 IV over 30 minutes, followed by cisplatin 25 mg/m2 IV over 30 minutes, followed by irinotecan 50 mg/m2 IV over 30 minutes on days 1 and 8 of each 3-week cycle until disease progression or unacceptable toxicity. Dose reductions were not permitted for bevacizumab although treatment could be held up to 2 months. If bevacizumab was discontinued, treatment with other agents could continue. When docetaxel, cisplatin, or irinotecan was held on day 1 of a cycle, all agents were held.
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
Avastin
Intervention Type
Drug
Intervention Name(s)
Docetaxel
Other Intervention Name(s)
Taxotere, Docefrez
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Other Intervention Name(s)
Platinol-AQ, Platinol
Intervention Type
Drug
Intervention Name(s)
Irinotecan
Other Intervention Name(s)
Camptosar
Primary Outcome Measure Information:
Title
10-month Progression-Free Survival Rate
Description
10-month progression-free survival rate is the probability of patients remaining alive and progression-free at 10-months from study entry estimated using Kaplan-Meier methods. Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.
Time Frame
Disease was evaluated radiologically at baseline and every 2 cycles on treatment; Treatment continued until disease progression or unacceptable toxicity. Relevant for this endpoint was disease status at 10 months.
Secondary Outcome Measure Information:
Title
Best Response
Description
Best response on treatment was based on RECIST 1.0 criteria: Complete Response (CR) is complete disappearance of all target lesions; Partial Response (PR) is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. Both require confirmation no fewer than 4 weeks apart. CR/PR assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions. Progressive disease (PD) is at least a 20% increase in the sum of longest diameter of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions. Stable disease is defined as any condition not meeting above criteria.
Time Frame
Disease was evaluated radiologically at baseline and every 2 cycles on treatment. Treatment continued until disease progression or unacceptable toxicity. Treatment duration was a median of 6 cycles/18 weeks given 3-week cycle length (range 1-26 cycles).
Title
Overall Survival
Description
Overall survival is defined as the time from study entry to death or date last known alive and estimate using Kaplan-Meier (KM) methods.
Time Frame
Patients in the study cohort were followed for a median of 12.2 month (up to 40 months).
Title
Progression-Free Survival
Description
Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) requiring removal from the study or death. Patients alive and progression-free at last follow-up are censored. Per RECIST 1.0 criteria: progressive disease is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.
Time Frame
Disease was evaluated radiologically at baseline and every 2 cycles on treatment. Treatment continued until disease progression or unacceptable toxicity. Treatment duration was a median of 6 cycles/18 weeks given 3-week cycle length (range 1-26 cycles).

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically confirmed, unresectable esophageal or gastric carcinoma (carcinoma=adenocarcinoma or squamous cell carcinoma) Measurable disease greater than or equal to 1 cm (longest diameter) by spiral computed tomography (CT) scan or 2 cm or greater by other radiographic technique Lesions must be measurable in at least one dimension Bone lesions, ascites, and effusions are not measurable 18 years of age or older ECOG performance status 0 or 1 Life expectancy of at least 12 weeks Adequate bone marrow function Adequate renal function Adequate liver function Exclusion Criteria: Prior chemotherapy (except as part of pre- or post-operative therapy, completed more than 1 year prior to start day of this protocol) History of severe hypersensitivity to bevacizumab, docetaxel, cisplatin, irinotecan, or drugs formulated with polysorbate 80 Current, recent (within 4 weeks) or planned participation in an experimental drug study Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, or anticipation of need for major surgical procedure during the course of the study Minor surgical procedures, such as fine needle aspirations, port-a-cath placement, or core biopsies within 7 days prior to Day 0 of study Myocardial infarction or stroke in past 6 months Blood pressure of > 150/100 mmHg Unstable angina New York Heart Association (NYHA) grade II or greater congestive heart failure Clinically significant peripheral vascular disease Persistent bleeding from primary tumor, while off anticoagulants, requiring repeated transfusions Evidence of bleeding diathesis or coagulopathy Uncontrolled serious medical or psychiatric illness Uncontrolled diarrhea Peripheral neuropathy > grade 1 Clinically apparent central nervous system metastases or carcinomatous meningitis Other active malignancy other than non-melanoma skin cancer or in situ cervical carcinoma. Urine protein: creatinine ratio of 1.0 or greater at screening History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 1 Serious non-healing wound, ulcer, or bone fracture Pregnant or breast-feeding
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter Enzinger, MD
Organizational Affiliation
Dana-Farber Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Docetaxel, Cisplatin, Irinotecan and Bevacizumab (TPCA) in Metastatic Esophageal and Gastric Cancer

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