A Study to See if hENT1 Testing on Tumour Tissue Can Predict Response to Treatment With Gemcitabine Chemotherapy and if a Different Chemotherapy Called FOLFOX is Better Than Gemcitabine in Metastatic Pancreas Cancer

NCT01586611 | Unknown Phase 3

• 1 other identifier: Panc001
• Study Type: interventional
• Target: 175
• Locations: 1 country
• Sites: 1

Brief Summary

Chemotherapy is often used to help shrink the cancer temporarily and may improve survival for patients with incurable pancreas cancer that has spread to other organs. In Canada, the gemcitabine chemotherapy is used to treat pancreas cancer that has spread. The combination of oxaliplatin with other chemotherapies, including 5-fluorouracil, leucovorin, and irinotecan has also been studied and has benefit for patients with advanced pancreas cancer. To date, there is no test that can be done on a patient's tumour to tell if chemotherapy will work in pancreatic cancer. Human equilibrative nucleoside transporter 1 (hENT1) has been shown to be a possible predictor that gemcitabine may or may not work but this needs to be proven in a randomized study where patients get treated with gemcitabine or a different kind of chemotherapy while their tumours get tested for hENT1. This study is being done because we want to prove that hENT1 can predict if gemcitabine will work in advanced pancreas cancer and if it can, we also would like to show that a different chemotherapy combination called FOLFOX (a combination of 5-fluorouracil, leucovorin, and oxaliplatin) will be helpful for patients whose tumours don't have hENT1.

Conditions

Metastatic Pancreas Cancer

Outcome Measures

Primary Outcomes (1)

• The difference Progression Free Survival (PFS) between Gemcitabine and FOLFOX treated patients in hENT1 high and hENT1 low pancreatic adenocarcinoma.

  Progression free survival will be measured from the date of diagnosis to the date of progression or death, patients who did not progress or is alive at the last date of follow-up will be censored for the analysis. Kaplan-Meier method will be used to estimate the survival function and log-rank test will be utilized to compare the study arms. The median PFS and the corresponding 95% confidence interval will be used for reporting purpose. The hazard ratio and the corresponding 95% two-sided confidence interval using Cox-proportional hazard regression will be presented.

  2 Years

Secondary Outcomes (4)

• The difference in overall response rate (ORR) between the two treatment arms.

  2 years

• The rate of disease control (DCR), defined as the sum of complete response rate (RR), partial RR, and stable disease between the two treatment arms.

  2 Years

• The difference in overall survival (OS) between the two treatment arms.

  2 Years

• Health-related quality of life (HRQL) parameters in patients with metastatic pancreas adenocarcinoma treated in both treatment arms.

  2 Years

Study Arms (2)

Gemcitabine

ACTIVE COMPARATOR

Cycles to be 4 weeks in length Gemcitabine 1000 mg/m2 IV weekly for 3 weeks then one week off

Drug: Gemcitabine

FOLFOX

EXPERIMENTAL

Cycles to be 2 weeks in length Oxaliplatin 100 mg/m2 IV day 1 Leucovorin 400 mg/m2 IV day 1 5-FUl 400 mg/m2 IV day 1 5-FU 2400 mg/m2 IV continuous infusion over 46 hours starting day 1

Drug: 5FU, leucovorin, oxaliplatin

Interventions

5FU, leucovorin, oxaliplatin DRUG

Oxaliplatin 100 mg/m2 IV day 1 Leucovorin 400 mg/m2 IV day 1 5-FUl 400 mg/m2 IV day 1 5-FU 2400 mg/m2 IV continuous infusion over 46 hours starting day 1

FOLFOX

Gemcitabine DRUG

1000 mg/m2 IV weekly for 3 weeks then one week off

Gemcitabine

Eligibility Criteria

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

You may qualify if:

• Histologically documented metastatic pancreatic adenocarcinoma not previously treated with palliative systemic therapy
• Metastatic disease based on the presence of clinically and/or radiologically documents Measurable disease base on RECIST.
• Adequate tissue (core biopsy) available for IHC testing of hENT1. This may be from primary tumour or metastatic site. Fine needle aspiration biopsies will not be allowed. Histological/cytological confirmation of tissue to ensure sufficient material is available for hENT1 analysis by the Cross Cancer Institute is required prior to starting a patient on study. Biopsies from metastatic sites must be obtained ≥ 3 months after any adjuvant chemotherapy (if applicable). If a patient has had previous surgical resection of their primary tumours, that tissue can be utilized. Tissue sufficient for preparing ≥ 10 unstained slides for central storage and testing is required.
• ECOG performance status of 0 - 1.
• Age ≥ 18 years.
• Life expectancy of at least 3 months based on discretion of treating oncologist.
• Adequate hematologic function defined by the following laboratory parameters:
• Hemoglobin ≥ 100
• Platelet count ≥ 100
• Absolute granulocyte count ≥ 1.5
• Adequate hepatic and renal function defined by the following laboratory parameters:
• AST and ALT ≤ 2.5 X upper limit of institutional normal (≤ 5 if liver metastases)
• bilirubin ≤ upper limit of institutional normal
• calculated creatinine clearance of ≥ 50 mL/min using the Cockcroft-Gault formula, if just below 50 mL/min based on this formula then GFR ≥ 50 mL/min as determined by 24 hr urine collection
• Patients who have received prior chemotherapy or radiation delivered as part of initial curative therapy (i.e. neoadjuvant or adjuvant chemotherapy administered alone and/or concurrently delivered with radiation and/or surgery) are permitted as long as that treatment was completed at least 6 months prior to study start date.

You may not qualify if:

• Patients who have received prior palliative chemotherapy for their metastatic pancreatic adenocarcinoma.
• Radical pancreatic resections (e.g. Whipple procedure) are not allowed \< 6 months prior to randomization. Exploratory laparotomy, palliative (e.g. bypass) surgery, or other procedures (e.g. stents) are not allowed \< 14 days prior to randomization. In any of the above cases, patients must be adequately recovered and stable prior to randomization.
• Prior treatment with \> 6 cycles of traditional alkylating agent-based chemotherapy, \> 2 cycles of carboplatin-based chemotherapy, prior treatment with irinotecan or oxaliplatin chemotherapy, or concurrent treatment with other experimental drugs or anti-cancer therapy.
• Curative radiation treatment to the pelvis or radiation therapy to ≥ 25% of bone marrow stores.
• Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, short gut syndrome, or history of bowel obstruction due to peritoneal metastases.
• Previous or concurrent malignancies, excluding curatively treated in situ carcinoma of the cervix or non-melanoma skin cancer, unless at least 5 years have elapsed since last treatment and the patient is considered cured.
• Any serious medical condition within 6 months prior to study entry such as myocardial infarction, uncontrolled congestive heart failure, unstable angina, active cardiomyopathy, unstable ventricular arrhythmia, cerebrovascular diseases, uncontrolled hypertension, uncontrolled diabetes, uncontrolled psychiatric disorder, serious infection, active peptic ulcer disease, or other medical condition that may be aggravated by treatment.
• Known dihydropyrimidine dehydrogenase (DPD) deficiency.
• Pre-existing neuropathy ≥ grade 2 from any cause.
• Patients with unstable metastasis to the central nervous system are excluded. Patients who have treated brain metastasis and are off steroids, anticonvulsants, and have documented stability of lesions for at least 3 months may be eligible. A CT scan or MRI is NOT required to rule out brain metastases unless there is clinical suspicion of CNS involvement.
• Pregnant or lactating women; women of child bearing potential must have a negative serum pregnancy test within 7 days of trial registration. Women or men of child bearing potential must use effective contraception (defined by the treating physician) which must be documented in study CRFs.
• Any other reason the investigator considers the patient should not participate in the study.

Sponsors & Collaborators

• AHS Cancer Control Alberta: lead

Study Sites (1)

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

RECRUITING

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Fluorouracil; Leucovorin; Oxaliplatin; Gemcitabine

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; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides

Study Officials

• Neil S. Chua, MD, FRCPC

  Cross Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Neil S Chua, MD, FRCPC

CONTACT

780-432-8340; neil.chua@albertahealthservices.ca

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2012
• First Posted: April 27, 2012
• Study Start: June 1, 2012
• Primary Completion: April 1, 2015
• Study Completion: June 1, 2015
• Last Updated: October 2, 2014

Record last verified: 2014-10

Locations

CA (1)