A randomised phase II study evaluating potential predictive biomarkers in the treatment of locally advanced and metastatic pancreatic cancer
A randomised phase II study evaluating potential predictive biomarkers and examining the efficacy and safety of oxaliplatin, 5-fluorouracil and leucovorin (as mFOLFOX6) compared to gemcitabine in the treatment of metastatic pancreatic cancer.
Australasian Gastrointestinal Trials Group (AGITG)
80 participants
Apr 17, 2012
Interventional
Conditions
Summary
This study looks at whether testing for 'biomarkers' may be used to select the best treatment for patients with metastatic pancreatic cancer. A biomarker is a biological characteristic that can be measured in tumour tissue or blood, which may provide information on the behaviour of cancer or help predict the likely effect of a given treatment. We know that not all cancers or patients are the same, and that some patients may respond better to certain treatments. This study will help increase our understanding of how we might be able to select treatments to suit individual patients and their cancers. By doing this we hope to obtain the best outcomes for future patients while minimising side effects from treatment. Who is it for? You can join this study if you have radiologically and histologically confirmed metastatic pancreatic adenocarcinoma, confirmed by biopsy. This is a phase II multicentre, randomised, open label study to evaluate biomarker directed treatment of metastatic pancreatic cancer. Trial Details Participants will be in two groups. Group 1 will receive Gemcitabine, and Group 2 will receive a combination of Oxaliplatin, Leucovorin and 5-fluorouracil (mFOLFOX6). Treatment will continue as long as it seems to be helping, provided participants do not have troublesome side effects. Through this study we hope to gain information about the following: 1) Can testing for hENT1 help us to identify patients who are more likely to benefit from initial treatment with gemcitabine chemotherapy? 2) Is it possible to do the tests in patients quickly enough to enable use in routine clinical practice? 3) How effective is FOLFOX chemotherapy as treatment for metastatic pancreatic cancer? 4) Are there any other biomarkers in cancer cells or blood that may help us determine the best drug to use against an individual cancer? This randomised phase II exploratory study is vital in understanding the optimal design of future studies evaluating this novel approach to the management of pancreatic cancer, and may be expanded to a phase III study if this approach is validated.
Eligibility
Inclusion Criteria14
- Males or females with radiologically and histologically confirmed metastatic pancreatic adenocarcinoma. Eligibility of patients with suspected disease must be confirmed by core biopsy prior to randomisation.
- Adult patients; 18 years or over.
- No previous treatment, except:
- a. If adjuvant systemic therapy was received following resection, study entry is permissible if disease recurrence has occurred at least 6 months after completion of chemotherapy.
- b. Previous radiotherapy is permissible if disease progression has occurred outside the radiotherapy field and disease recurrence has occurred at least 6 months after completion of radiotherapy.
- c. Previous chemoradiotherapy is permissible if only radiosensitiser dose chemotherapy was used and disease progression has occurred outside of the radiotherapy field at least 6 months after completion of treatment.
- Informed consent for all trial procedures, including:
- a. Consent to undergo core biopsy to obtain tissue for biomarker analysis unless suitable archived paraffin embedded tissue (e.g. surgical specimen) is already available for human equilibrative nucleoside transporter 1 (hENT1) testing and other planned translational studies.
- b. Consent for collection of peripheral blood for pharmacogenomic/pharmacogenetic analysis.
- World Health Organisation (WHO) performance status 0-2.
- Adequate renal, hepatic and haematological function, defined as;
- a. Creatinine clearance (Cockcroft-Gault formula) >60mL/min
- b. Bilirubin <1.5 x Upper Limit of Normal (ULN), aspartate aminotransferase (AST) + alanine aminotransferase (ALT) <3.0 x ULN (or <5.0 x ULN with documented liver metastases)
- c. Haemoglobin >100 g/L, Platelets >150 x109/L and Neutrophils >1.5x 109/L
Exclusion Criteria10
- Previous systemic treatment for metastatic pancreatic cancer.
- Pregnant or lactating females or female patients of childbearing potential who have not been surgically sterilized or are without adequate contraceptive measures.
- Other active malignancy or primary malignancy diagnosed within the previous 5 years, except for treated squamous or basal cell carcinoma of skin or cervical carcinoma.
- Previous reactions to or suspected hypersensitivity to any of the investigational agents.
- Peripheral neuropathy of any cause, of grade 2 or worse by CTCAE v4.0 criteria.
- Seropositive for (Human Immunodeficiency Virus) HIV or Hepatitis C.
- Active Hepatitis B not suppressed with antiviral treatment.
- Symptomatic coronary or cardiac insufficiency.
- History of thromboembolism, myocardial infarction or cardiovascular accident within preceding 3 months. Patients who have experienced deep venous thrombosis or pulmonary embolism within previous 6 months must be maintained on therapeutic levels of anticoagulation.
- Diarrhoea >grade 2 and/or uncontrolled diarrhoea.
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Interventions
Patients randomised to the intervention arm will receive modified FOLFOX6 chemotherapy (mFOLFOX6). Each cycle of mFOLFOX6 will consist of: - Oxaliplatin 85mg/m2 given as an intravenous (IV) infusion on day 1 of a 2 week cycle. - 5-Flurouracil 400mg/m2 given as an IV infusion on day 1 of a 2 week cycle. - Leucovorin 400mg/m2 given as an IV infusion on day 1 of a 2 week cycle. - 5-Flurouracil 2400mg/m2 given as an IV continuous infusion over 46 hours, commencing on day 1 of a 2 week cycle. The cycle will be repeated every 2 weeks. Patients will continue their assigned treatment until progression, unacceptable toxicity or any of the reasons listed in protocol section 4.4.
Locations(1)
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ACTRN12610001047088