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

City of Hope

Status and phase: Active, not recruiting; Phase 1

Conditions: Unresectable Pancreatic Carcinoma; Pancreatic Adenocarcinoma; Stage IV Pancreatic Cancer AJCC v6 and v7; Stage III Pancreatic Cancer AJCC v6 and v7

Treatments: Dietary Supplement: Therapeutic Dietary Intervention; Drug: Gemcitabine Hydrochloride; Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Drug: Paclitaxel Albumin-Stabilized Nanoparticle Formulation; Drug: Metformin Hydrochloride

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02336087

NCI-2014-02612 (Registry Identifier)

14122 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 21 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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21 participants in 1 patient group

Treatment (gemcitabine, Abraxane, metformin, DS)

Experimental group

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.

Treatment:

Drug: Metformin Hydrochloride

Other: Quality-of-Life Assessment

Drug: Paclitaxel Albumin-Stabilized Nanoparticle Formulation

Other: Laboratory Biomarker Analysis

Dietary Supplement: Therapeutic Dietary Intervention

Drug: Gemcitabine Hydrochloride