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Phase IB/Randomized Phase II Study of Folfirinox Plus AMG-479 (Ganitumab) or Placebo in Patients With Previously Untreated, Metastatic Pancreatic Adenocarcinoma


Phase 1/Phase 2
18 Years
N/A
Not Enrolling
Both
Pancreatic Cancer

Thank you

Trial Information

Phase IB/Randomized Phase II Study of Folfirinox Plus AMG-479 (Ganitumab) or Placebo in Patients With Previously Untreated, Metastatic Pancreatic Adenocarcinoma


OBJECTIVES:

Primary

- To assess the safety and determine the maximally tolerated dose (MTD) of modified
FOLFIRINOX (mFOLFIRINOX) and ganitumab in patients with previously untreated,
metastatic pancreatic adenocarcinoma. (phase I)

- To compare overall survival of patients with previously untreated, metastatic
pancreatic adenocarcinoma who receive mFOLFIRINOX plus ganitumab versus mFOLFIRINOX
plus placebo. (phase II)

- To assess the convergent validity of each selected PRO-CTCAE item by comparing each
item at baseline between patients with ECOG performance status (PS) 0 vs 1. (phase II)

Secondary

- To compare objective response rate, duration of response, and progression-free survival
of patients with previously untreated, metastatic pancreatic adenocarcinoma who receive
mFOLFIRINOX plus ganitumab versus mFOLFIRINOX plus placebo.

- To compare treatment-related toxicity in patients with previously untreated, metastatic
pancreatic adenocarcinoma who receive mFOLFIRINOX plus ganitumab versus mFOLFIRINOX
plus placebo.

- To assess the responsiveness (sensitivity to change) of Patient-Reported Outcomes
(PRO)-CTCAE by comparing change scores within groups of patients as defined by changes
in ECOG PS at post-baseline administrations. (phase II)

- To compare the maximum post-baseline score for each PRO-CTCAE item per patient between
arms in the randomized phase II component of the study. (exploratory).

OUTLINE: This is a dose-escalation, phase IB study followed by a randomized phase II study.
Patients in the phase II study are stratified according to ECOG performance status of 0
versus 1.

- Phase IB: 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). After cohort 0, subsequent patients
also receive ganitumab IV over 1 hour on day 1. Treatment repeats every 14 days in the
absence of disease progression or unacceptable toxicity.

- Phase II: Patients are randomized to 1 of 2 treatment arms:

- Arm I: Patients receive mFOLFIRINOX as in Phase IB and ganitumab IV over 30-60
minutes on day 1.

- Arm II: Patients receive mFOLFIRINOX as in Phase IB and placebo IV over 30-60
minutes on day 1.

In both arms, treatment repeats every 14 days in the absence of disease progression or
unacceptable toxicity.

Patients randomized in the phase II component of the study may complete 16 Patient-Reported
Outcomes (PRO)-CTCAE items (measuring 8 symptoms) on paper on day 1 of all odd-numbered
courses (i.e., courses 1, 3, 5, etc.).

Tumor tissue and blood samples may be collected for correlative studies.

After completion of study therapy, patients are followed every 3 months for 3 years.

Inclusion Criteria


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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Dose-limiting toxicity (phase I)

Safety Issue:

Yes

Principal Investigator

Brain M. Wolpin, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Dana-Farber Cancer Institute

Authority:

United States: Food and Drug Administration

Study ID:

CDR0000716301

NCT ID:

NCT01473303

Start Date:

August 2012

Completion Date:

Related Keywords:

  • Pancreatic Cancer
  • stage IV pancreatic cancer
  • duct cell adenocarcinoma of the pancreas
  • Adenocarcinoma
  • Pancreatic Neoplasms

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