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

A Pilot Study of Gemcitabine, Abraxane, Metformin and a Standardized Dietary Supplement (DS) in Patients With Unresectable Pancreatic Cancer

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Pancreatic Adenocarcinoma; Unresectable Pancreatic Carcinoma; Stage III Pancreatic Cancer AJCC v6 and v7; Stage IV Pancreatic Cancer AJCC v6 and v7
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Drug: Gemcitabine Hydrochloride; Drug: Metformin Hydrochloride; Drug: Paclitaxel Albumin-Stabilized Nanoparticle Formulation; Dietary supplement: Therapeutic Dietary Intervention

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.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Medical Center
    • Rancho Cucamonga, California, United States, 91730
      • City of Hope Rancho Cucamonga
    • South Pasadena, California, United States, 91030
      • City of Hope South Pasadena
    • West Covina, California, United States, 91790
      • City of Hope West Covina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (gemcitabine, Abraxane, metformin, DS); 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.

Other: Laboratory Biomarker Analysis; Correlative studies; Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Drug: Gemcitabine Hydrochloride; Given IV; Other Names: dFdCyd; dFdC; Drug: Metformin Hydrochloride; Given PO; Other Names: Glucophage; Metformin HCl; Drug: Paclitaxel Albumin-Stabilized Nanoparticle Formulation; Given IV; Other Names: ABI-007; Abraxane; ABI 007; Dietary supplement: Therapeutic Dietary Intervention; Given PO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 24 months
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.	Up to 24 months
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.	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	Evaluated using the Kaplan-Meier methods.	Up to 24 months
Overall survival	Evaluated using the Kaplan-Meier methods.	Up to 24 months
Time to treatment failure	Evaluated using the Kaplan-Meier methods.	Up to 24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Analysis of biological correlates (Peripheral blood will be evaluated)	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.	Up to 24 months
Quality of life, assessed using the FACT-G questionnaire	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.	Up to 24 months

Collaborators and Investigators

• Sponsor: City of Hope Medical Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Vincent Chung, City of Hope Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2016
• Primary Completion (Actual): October 4, 2020
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: January 6, 2015
• First Submitted That Met QC Criteria: January 7, 2015
• First Posted (Estimated): January 12, 2015

Study Record Updates

• Last Update Posted (Actual): March 19, 2024
• Last Update Submitted That Met QC Criteria: March 18, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Metformin; Albumin-Bound Paclitaxel; Gemcitabine
• Other Study ID Numbers: 14122 (Other Identifier: City of Hope Medical Center); NCI-2014-02612 (Registry Identifier: CTRP (Clinical Trial Reporting Program))