Combination Chemotherapy With or Without Ganitumab in Treating Patients With Previously Untreated Metastatic Pancreatic Cancer

NCT01473303 | Withdrawn Phase 1

• 2 other identifiers: CALGB-81003CDR0000716301
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as fluorouracil, leucovorin calcium, irinotecan hydrochloride, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as ganitumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry cancer-killing substances to them. It is not yet known whether giving more than one drug (combination chemotherapy) is more effective with or without ganitumab in treating patients with pancreatic cancer. PURPOSE: This phase I/II trial is studying the best dose of combination chemotherapy and ganitumab and how well combination chemotherapy with or without ganitumab works in treating patients with previously untreated metastatic pancreatic cancer.

Conditions

Pancreatic Cancer

Keywords

stage IV pancreatic cancer; duct cell adenocarcinoma of the pancreas

Outcome Measures

Primary Outcomes (4)

• Dose-limiting toxicity (phase I)

• Maximum-tolerated dose (phase I)

• Overall survival (phase II)

• Convergent validity of each selected PRO-CTCAE item (phase II)

Secondary Outcomes (3)

• Objective response rate and duration of response between the mFOLFIRINOX plus ganitumab and the mFOLFIRINOX plus placebo arms (phase II)

• Progression-free survival (phase II)

• Responsiveness (sensitivity to change) of PRO-CTCAE (phase II)

Study Arms (2)

Arm I

EXPERIMENTAL

Patients receive oxaliplatin IV over 2 hours, irinotecan hydrochloride IV over 90 minutes, and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV over 48 hours beginning on day 2 (mFOLFIRINOX) and ganitumab IV over 30-60 minutes on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.

Biological: ganitumab; Drug: fluorouracil; Drug: irinotecan hydrochloride; Drug: leucovorin calcium; Drug: oxaliplatin

Arm II

EXPERIMENTAL

Patients receive mFOLFIRINOX as in arm I and placebo IV over 30-60 minutes on day 1.

Drug: fluorouracil; Drug: irinotecan hydrochloride; Drug: leucovorin calcium; Drug: oxaliplatin; Other: placebo; Other: questionnaire administration

Interventions

ganitumab BIOLOGICAL

Given IV

Arm I

fluorouracil DRUG

Given IV

Arm I; Arm II

irinotecan hydrochloride DRUG

Given IV

Arm I; Arm II

leucovorin calcium DRUG

Given IV

Arm I; Arm II

oxaliplatin DRUG

Given IV

Arm I; Arm II

placebo OTHER

Given IV

Arm II

questionnaire administration OTHER

Completed on paper

Arm II

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed pancreatic ductal adenocarcinoma * Metastatic disease to distant sites, as documented by CT scan or MRI * Patients with locally advanced disease are NOT eligible * At least one site of disease measurable by RECIST 1.1 criteria; defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 2 cm with conventional techniques or as ≥ 1 cm with spiral CT scan * No known CNS metastases or carcinomatous meningitis, as determined by physical examination and/or imaging studies * No suspected Gilbert syndrome or known homozygosity for the UGT1A1\*28 allele (UGT1A1 genotyping is not required for enrollment on this study; however, patients known to be homozygous for the UGT1A1\*28 allele are excluded) PATIENT CHARACTERISTICS: * ECOG performance status 0 or 1 * Neutrophils ≥ 1,500/μL * Platelet count ≥ 100,000/μL * Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min * Total bilirubin ≤ 1.5 x upper limit of normal (ULN) * AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN * INR ≤ 1.5 * Blood glucose level ≤ 160 mg/dL * Patients with non-fasting blood glucose \> 160 mg/dL must have a fasting blood glucose ≤ 160 mg/dL to be eligible * Patients with diabetes mellitus are allowed at the discretion of the treating investigator, if blood sugars are felt to be under appropriate control * Not pregnant or nursing * Negative serum or urine pregnancy test * No malignancy (other than non-melanoma skin cancer or carcinoma in situ of the cervix) diagnosed within the past 3 years or any currently active malignancy * A malignancy is considered not "active" if all anti-cancer therapies were completed \> 3 years before enrollment and there is no current evidence of persistent disease * No neurosensory or neuromotor toxicity ≥ grade 2 * No known allergy to platinum compounds or E. coli-derived products (e.g., filgrastim, humulin, insulin, or L-asparaginase) * No colonic or small bowel disorders with uncontrolled symptoms at baseline (for example, \> 3 watery or soft stools daily in patients without colostomy or ileostomy) * Patients with colostomy or ileostomy can be enrolled at the discretion of the investigator * No history of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within 6 months of registration * No HIV-positive patients with a prior history of AIDS-defining illness * No HIV-positive patients with a CD4 count of \< 450 cells/mm³ at any point prior to study * Anti-retroviral therapy must be discontinued during study treatment * No known positivity for chronic infection with B virus (HBV) PRIOR CONCURRENT THERAPY: * Prior treatment with chemotherapy or radiotherapy for resected, locally advanced or metastatic pancreatic cancer is NOT allowed * No prior treatment with inhibitors of the insulin-like growth factor 1 receptor * No prior treatment with radiotherapy to greater than 25% of bone marrow * Palliative radiation therapy may NOT be administered while a subject is on the study * No major surgery within 4 weeks of the start of study treatment * Patients must have recovered from the side effects of any major surgery at the start of study treatment * Major surgery is defined as those surgeries that require general anesthesia * Insertion of a vascular access device or endobiliary stent is NOT considered major surgery * No percutaneous biliary drain (endobiliary stents are allowed) * Warfarin for INR goal \> 1.5 is prohibited * Patients on warfarin with INR goal of ≤ 1.5 are eligible * Hormones or other chemotherapeutic agents may NOT be administered except for steroids given for adrenal failure; hormones administered for non-disease-related conditions (e.g., insulin for diabetes); and intermittent use of dexamethasone as an antiemetic or for the prevention or treatment of ganitumab infusion reactions * Patients receiving anti-retroviral therapy must discontinue such therapy while receiving study treatment

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Alliance for Clinical Trials in Oncology: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

ganitumab; Fluorouracil; Irinotecan; Leucovorin; Oxaliplatin

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Camptothecin; Alkaloids; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals

Study Officials

• Brain Wolpin, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2011
• First Posted: November 17, 2011
• Study Start: August 1, 2012
• Primary Completion: August 1, 2012
• Last Updated: June 28, 2016

Record last verified: 2016-06