J13146: An Exploratory Study of Metformin With or Without Rapamycin as Maintenance Therapy After Induction Chemotherapy in Subjects with Metastatic Pancreatic Adenocarcinoma
Primary Objectives To determine the safety and feasibility of administering metformin with or without rapamycin in subjects with metastatic pancreatic ductal adenocarcinoma (PDA) after disease stabilization on chemotherapy. Exploratory Objectives To evaluate fludeoxyglucose (FDG) uptake in metastatic PDA subjects treated with metformin with or without rapamycin. To measure HIF1ï?¡ and glutaminate expression in tumors of subjects treated with metformin with or without rapamycin. To evaluate extracellular matrix by histology in tumors of subjects treated with metformin with or without rapamycin. To measure mammalian target of rapamycin (mTOR) activity in peripheral blood mononuclear cells (PBMC) of subjects treated with metformin with or without rapamycin. To estimate response rate (RR), time to progression (TTP), progression-free survival (PFS) and overall survival (OS) in subjects with metastatic PDA treated with metformin with or without rapamycin. To measure tumor marker kinetics (CA 19-9) in subjects treated with metformin with or without rapamycin.
Eligibility Criteria Subject must have histologically or cytologically confirmed metastatic pancreatic adenocarcinoma. Subjects with islet cell neoplasms are excluded. Subjects with mixed histology will be excluded. Subject must have one or more tumors measurable by CT scan using RECIST 1.1 criteria at the time of eligibility determination. MRI is acceptable if a CT scan is contraindicated. Subject must have received 6 months of FOLFIRINOX or a gemcitabine-containing regimen. Subject should have stable disease or better on 2 scans taken at least 6 weeks apart. If applicable, subject should also have a stable or declining CA19-9 based on measurements based at least 2 weeks apart with a less than 20% rise considered stable). Subject with a lesion that is amenable to biopsy must agree to have a biopsy at baseline and 2 on treatment biopsies if amenable and considered reasonably safe to obtain. Age greater than 18 years. ECOG performance status 0 or 1. ECOG 0 indicates that the subject is fully active and able to carry on all pre-disease activities without restriction; ECOG 1 indicates that the subject is restricted in physically strenuous activity but is ambulatory and able to carry out work of a light or sedentary nature Life expectancy of greater than 12 weeks. Subject must have adequate organ and marrow function as defined below: ï?WBC greater than 3,000/mcL ï?Absolute Neutrophil Count greater than 1,000/mcL ï?Platelets greater than 90 x 109/L ï?Hemoglobin ï?³8 g/dL ï?Total Bilirubinwithin normal institutional limits ï?AST(SGOT)/ALT(SGPT)ï?£ 2.5 x ULN ï?Creatininewithin normal institutional limits OR ï?Creatinine clearance greater than 60 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal. Oxygen saturation on room air greater than 92 % by pulse oximetry. (Subjects on intermittent or continuous supplemental oxygen are excluded). Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Ability to understand and the willingness to sign a written informed consent document.
Subjects with metastatic PDA who have received FOLFIRINOX or a gemcitabine-containing regimen and have achieved stable disease or better will be enrolled onto this study. Subjects should have had at least 6 months of chemotherapy and decline continuation of chemotherapy and should have stable disease or better on 2 scans taken at least 6 weeks apart. If applicable, subjects should also have a stable or declining CA19-9. Twenty-two subjects will be randomized in a 1:1 ratio to metformin (Arm A) or metformin + rapamycin (Arm B). Subjects will be stratified according to their prior chemotherapy regimen: FOLFIRINOX or a gemcitabine-containing regimen. Treatments will be administered orally on a 28 day cycle. Metformin will be administered 850mg twice daily and rapamycin will be administered 4mg daily.
05/29/2015 04:01 AM