search
Back to results

Gemcitabine Hydrochloride, Paclitaxel Albumin-Stabilized Nanoparticle Formulation, Metformin Hydrochloride, and a Standardized Dietary Supplement in Treating Patients With Pancreatic Cancer That Cannot be Removed by Surgery

Primary Purpose

Pancreatic Adenocarcinoma, Unresectable Pancreatic Carcinoma, Stage III Pancreatic Cancer AJCC v6 and v7

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Gemcitabine Hydrochloride
Paclitaxel Albumin-Stabilized Nanoparticle Formulation
Metformin Hydrochloride
Therapeutic Dietary Intervention
Laboratory Biomarker Analysis
Quality-of-Life Assessment
Sponsored by
City of Hope Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pancreatic Adenocarcinoma

Eligibility Criteria

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

Inclusion Criteria:

  • Patients must have a histologic diagnosis of pancreatic adenocarcinoma
  • Patient must have unresectable disease
  • Patients must not have received prior chemotherapy except for the following circumstances; gemcitabine and capecitabine chemotherapy given in the adjuvant setting is allowed if the recurrence is greater than 6 months from the completion of chemotherapy; radiation sensitizing doses of 5-fluororuracil or capecitabine are allowed as part of adjuvant treatment and recurrence must be documented greater than 6 months from the completion of adjuvant therapy
  • Computed tomography (CT) or magnetic resonance imaging (MRI) scan must be obtained within 4 weeks prior to study entry
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  • Absolute neutrophil count > 1,500/mcl
  • Platelet count > 100,000/mcl
  • Creatinine < 1.4 mg/dl and/or a measured creatinine clearance > 60 cc/min
  • Bilirubin < 1.4 mg/dl
  • Alanine aminotransferase (ALT), aspartate aminotransferase (AST) no greater than 3.0 times the upper limit of normal
  • Patients currently being treated for severe infections or who are recovering from major surgery or other intercurrent illnesses are ineligible until recovery is deemed complete by the investigator
  • Patients must not be pregnant or nursing; women and men of reproductive potential must have agreed to use an effective contraceptive method
  • All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
  • Patients must be able to swallow pills and must not have malabsorption problems or ongoing nausea and vomiting that would affect oral treatment
  • No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years
  • Patients currently taking metformin will be eligible
  • Patients allergic to eggs are not eligible
  • Patients taking additional dietary/herbal supplements (excluding Senekot) outside of this protocol and refusing to stop are not eligible
  • Patients requiring warfarin are not eligible

Sites / Locations

  • City of Hope Medical Center
  • City of Hope Rancho Cucamonga
  • City of Hope South Pasadena
  • City of Hope West Covina

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (gemcitabine, Abraxane, metformin, DS)

Arm Description

Patients receive gemcitabine hydrochloride and paclitaxel albumin-stabilized nanoparticle formulation IV on days 1, 8, and 15. Patients also receive metformin hydrochloride PO BID starting day -6 and dietary supplement PO BID starting day -3. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Feasibility of the combination of gemcitabine hydrochloride, paclitaxel albumin-stabilized nanoparticle formulation, metformin hydrochloride, and a dietary supplement
Feasibility is defined at 1 or fewer patients experiencing a dose limiting toxicity within the first 6 patients.
Compliance of the combination of gemcitabine hydrochloride, paclitaxel albumin-stabilized nanoparticle formulation, metformin hydrochloride, and a dietary supplement (percent of patients who are fully compliant)
The percent of patients who are fully compliant in the first week will be estimated with a 95% confidence interval. The compliance will be measured similarly for each course prior to study treatment discontinuation. The impact of less than full compliance (both during the lead-in period and during chemotherapy) on the biomarkers and outcome, and qualitatively study patient reasons and specific supplement patterns related to non-compliance will be explored.
Toxicity of the combination of gemcitabine hydrochloride, paclitaxel albumin-stabilized nanoparticle formulation, metformin hydrochloride, and a dietary supplement (National Cancer Institute Common Terminology for Adverse Events criteria version 4)
Summarized using the National Cancer Institute Common Terminology for Adverse Events criteria version 4. Tables will summarize the highest grade per patient that is possibly related to treatment, and the number of patients requiring dose modifications will also be presented.

Secondary Outcome Measures

Progression-free survival
Evaluated using the Kaplan-Meier methods.
Overall survival
Evaluated using the Kaplan-Meier methods.
Time to treatment failure
Evaluated using the Kaplan-Meier methods.

Full Information

First Posted
January 6, 2015
Last Updated
March 17, 2023
Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT02336087
Brief Title
Gemcitabine Hydrochloride, Paclitaxel Albumin-Stabilized Nanoparticle Formulation, Metformin Hydrochloride, and a Standardized Dietary Supplement in Treating Patients With Pancreatic Cancer That Cannot be Removed by Surgery
Official Title
A Pilot Study of Gemcitabine, Abraxane, Metformin and a Standardized Dietary Supplement (DS) in Patients With Unresectable Pancreatic Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 14, 2016 (Actual)
Primary Completion Date
October 4, 2020 (Actual)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This pilot phase I trial studies the side effects of gemcitabine hydrochloride, nab-paclitaxel, metformin hydrochloride, and a standardized dietary supplement in treating patients with pancreatic cancer that cannot be removed by surgery. Drugs used in chemotherapy, such as gemcitabine hydrochloride and paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Metformin hydrochloride, used for diabetes, may also help kill cancer cells. Dietary supplements (curcumin, vitamin D, vitamin K2, vitamin K1, B-6, high selenium broccoli sprouts, epigallocatechin gallate, L-carnitine, garlic extract, genistein, zinc amino chelate, mixed toxopherols, ascorbic acid, D-limonene) can block different targets in the cancer cell simultaneously and may slow down cancer growth. Giving gemcitabine hydrochloride, paclitaxel albumin-stabilized nanoparticle formulation, and metformin hydrochloride with a dietary supplement may work better in treating patients with pancreatic cancer that cannot be removed by surgery.
Detailed Description
PRIMARY OBJECTIVES: I. To assess the compliance, toxicity and feasibility of administering gemcitabine hydrochloride (gemcitabine), nab-paclitaxel (abraxane), metformin hydrochloride (metformin), and the dietary supplement (DS). SECONDARY OBJECTIVES: I. To assess the response rate associated with this combination therapy in pancreatic cancer patients. II. To assess the progression-free survival and overall survival of all patients who start protocol therapy, and describe the outcomes based on measures of compliance during the lead-in week, and compliance with supplement during chemotherapy. III. To collect and analyze peripheral blood and pre-treatment biopsy samples for an exploratory analysis of biological correlatives. IV. To assess quality of life utilizing the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire. OUTLINE: Patients receive gemcitabine hydrochloride and paclitaxel albumin-stabilized nanoparticle formulation intravenously (IV) on days 1, 8, and 15. Patients also receive metformin hydrochloride orally (PO) twice daily (BID) starting day -6 and dietary supplement PO BID starting day -3. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Adenocarcinoma, Unresectable Pancreatic Carcinoma, Stage III Pancreatic Cancer AJCC v6 and v7, Stage IV Pancreatic Cancer AJCC v6 and v7

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (gemcitabine, Abraxane, metformin, DS)
Arm Type
Experimental
Arm Description
Patients receive gemcitabine hydrochloride and paclitaxel albumin-stabilized nanoparticle formulation IV on days 1, 8, and 15. Patients also receive metformin hydrochloride PO BID starting day -6 and dietary supplement PO BID starting day -3. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
Gemcitabine Hydrochloride
Other Intervention Name(s)
dFdC, dFdCyd
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Paclitaxel Albumin-Stabilized Nanoparticle Formulation
Other Intervention Name(s)
ABI 007, ABI-007, Abraxane
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Metformin Hydrochloride
Other Intervention Name(s)
Glucophage, Metformin HCl
Intervention Description
Given PO
Intervention Type
Dietary Supplement
Intervention Name(s)
Therapeutic Dietary Intervention
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
Quality-of-Life Assessment
Other Intervention Name(s)
Quality of Life Assessment
Intervention Description
Ancillary studies
Primary Outcome Measure Information:
Title
Feasibility of the combination of gemcitabine hydrochloride, paclitaxel albumin-stabilized nanoparticle formulation, metformin hydrochloride, and a dietary supplement
Description
Feasibility is defined at 1 or fewer patients experiencing a dose limiting toxicity within the first 6 patients.
Time Frame
Up to 24 months
Title
Compliance of the combination of gemcitabine hydrochloride, paclitaxel albumin-stabilized nanoparticle formulation, metformin hydrochloride, and a dietary supplement (percent of patients who are fully compliant)
Description
The percent of patients who are fully compliant in the first week will be estimated with a 95% confidence interval. The compliance will be measured similarly for each course prior to study treatment discontinuation. The impact of less than full compliance (both during the lead-in period and during chemotherapy) on the biomarkers and outcome, and qualitatively study patient reasons and specific supplement patterns related to non-compliance will be explored.
Time Frame
Up to 24 months
Title
Toxicity of the combination of gemcitabine hydrochloride, paclitaxel albumin-stabilized nanoparticle formulation, metformin hydrochloride, and a dietary supplement (National Cancer Institute Common Terminology for Adverse Events criteria version 4)
Description
Summarized using the National Cancer Institute Common Terminology for Adverse Events criteria version 4. Tables will summarize the highest grade per patient that is possibly related to treatment, and the number of patients requiring dose modifications will also be presented.
Time Frame
Up to 24 months
Secondary Outcome Measure Information:
Title
Progression-free survival
Description
Evaluated using the Kaplan-Meier methods.
Time Frame
Up to 24 months
Title
Overall survival
Description
Evaluated using the Kaplan-Meier methods.
Time Frame
Up to 24 months
Title
Time to treatment failure
Description
Evaluated using the Kaplan-Meier methods.
Time Frame
Up to 24 months
Other Pre-specified Outcome Measures:
Title
Analysis of biological correlates (Peripheral blood will be evaluated)
Description
Peripheral blood will be evaluated. Standard descriptive methods will be used to summarize the baseline levels and the changes from baseline (i.e. after treatment) in order to examine whether observed patterns are consistent with hypothesized patterns.
Time Frame
Up to 24 months
Title
Quality of life, assessed using the FACT-G questionnaire
Description
Standard descriptive methods will be used to summarize the baseline levels and the changes from baseline (i.e. after treatment) in order to examine whether observed patterns are consistent with hypothesized patterns.
Time Frame
Up to 24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have a histologic diagnosis of pancreatic adenocarcinoma Patient must have unresectable disease Patients must not have received prior chemotherapy except for the following circumstances; gemcitabine and capecitabine chemotherapy given in the adjuvant setting is allowed if the recurrence is greater than 6 months from the completion of chemotherapy; radiation sensitizing doses of 5-fluororuracil or capecitabine are allowed as part of adjuvant treatment and recurrence must be documented greater than 6 months from the completion of adjuvant therapy Computed tomography (CT) or magnetic resonance imaging (MRI) scan must be obtained within 4 weeks prior to study entry Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 Absolute neutrophil count > 1,500/mcl Platelet count > 100,000/mcl Creatinine < 1.4 mg/dl and/or a measured creatinine clearance > 60 cc/min Bilirubin < 1.4 mg/dl Alanine aminotransferase (ALT), aspartate aminotransferase (AST) no greater than 3.0 times the upper limit of normal Patients currently being treated for severe infections or who are recovering from major surgery or other intercurrent illnesses are ineligible until recovery is deemed complete by the investigator Patients must not be pregnant or nursing; women and men of reproductive potential must have agreed to use an effective contraceptive method All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines Patients must be able to swallow pills and must not have malabsorption problems or ongoing nausea and vomiting that would affect oral treatment No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years Patients currently taking metformin will be eligible Patients allergic to eggs are not eligible Patients taking additional dietary/herbal supplements (excluding Senekot) outside of this protocol and refusing to stop are not eligible Patients requiring warfarin are not eligible
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Vincent Chung
Organizational Affiliation
City of Hope Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
City of Hope Rancho Cucamonga
City
Rancho Cucamonga
State/Province
California
ZIP/Postal Code
91730
Country
United States
Facility Name
City of Hope South Pasadena
City
South Pasadena
State/Province
California
ZIP/Postal Code
91030
Country
United States
Facility Name
City of Hope West Covina
City
West Covina
State/Province
California
ZIP/Postal Code
91790
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Gemcitabine Hydrochloride, Paclitaxel Albumin-Stabilized Nanoparticle Formulation, Metformin Hydrochloride, and a Standardized Dietary Supplement in Treating Patients With Pancreatic Cancer That Cannot be Removed by Surgery

We'll reach out to this number within 24 hrs