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

Pancreatic Adenocarcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02336087
• Other study ID #: 14122
• Secondary ID: NCI-2014-0261214
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: January 14, 2016
• Est. completion date: December 31, 2024

Study information

• Verified date: March 2024
• Source: City of Hope Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 21
• Est. completion date: December 31, 2024
• Est. primary completion date: October 4, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Pancreatic Adenocarcinoma
• Pancreatic Neoplasms
• Stage III Pancreatic Cancer AJCC v6 and v7
• Stage IV Pancreatic Cancer AJCC v6 and v7
• Unresectable Pancreatic Carcinoma

Intervention

Drug:
• Gemcitabine Hydrochloride
Given IV
• Paclitaxel Albumin-Stabilized Nanoparticle Formulation
Given IV
• Metformin Hydrochloride
Given PO

Dietary Supplement:
• Therapeutic Dietary Intervention
Given PO

Other:
• Laboratory Biomarker Analysis
Correlative studies
• Quality-of-Life Assessment
Ancillary studies

Locations

Country	Name	City	State
United States	City of Hope Medical Center	Duarte	California
United States	City of Hope Rancho Cucamonga	Rancho Cucamonga	California
United States	City of Hope South Pasadena	South Pasadena	California
United States	City of Hope West Covina	West Covina	California

Sponsors (2)

Lead Sponsor	Collaborator
City of Hope Medical Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Primary	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
Primary	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
Primary	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	Progression-free survival	Evaluated using the Kaplan-Meier methods.	Up to 24 months
Secondary	Overall survival	Evaluated using the Kaplan-Meier methods.	Up to 24 months
Secondary	Time to treatment failure	Evaluated using the Kaplan-Meier methods.	Up to 24 months