Phase I-II Trial of Gemcitabine Plus Nab-paclitaxel (GemBrax) Followed by Folfirinox as First Line Treatment of Patients With Metastatic Pancreatic Adenocarcinoma.
Overview
- Phase
- Phase 1
- Intervention
- GEMBRAX
- Conditions
- Metastatic Pancreatic Adenocarcinoma
- Sponsor
- Institut du Cancer de Montpellier - Val d'Aurelle
- Enrollment
- 78
- Locations
- 1
- Primary Endpoint
- Determination of the MTD
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
Based on conventional chemotherapy approach, data have indicated that the Folfirinox regimen is more effective and tolerate than the treatment by Gemcitabine alone in patients with metastatic pancreatic adenocarcinoma. A recent study combining gemcitabine and nab paclitaxel improve the objective response rate.
Primary objective of this study is to identify the maximun tolerated dose and the recommended phase II dose of first line treatment combining gemcitabine plus nab-paclitaxel followed by folfirinox in metastatic pancreatic adenocarcinoma.
Detailed Description
Estimated enrollment: Phase I: 60 Phase II: 53 Study start Date: August 2013 Estimated study completion date: March 2016 Treatment: Gembrax: albumin-bound paclitaxel over 30 minutes IV followed by Gemcitabine 10mg/m²/min IV on day 1, 8 and 15 followed by 2 weeks of rest Folfirinox: Oxaliplatin IV associated with LeucovorinIV. After the end of leucovorin administration, bolus injection of 5FU and subsequent continuous 5FU 46-hour infusion at day 29 and 43. Day 1=Day 57
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas. The definitive diagnosis of metastatic pancreatic adenocarcinoma will be made by integrating the histopathological data within the context of the radiologic data.
- •Initial diagnosis of metastatic disease must have occurred ≤6 weeks prior to inclusion in the study.
- •One or more metastatic tumors measurable metastatic lesions by CT scan of the abdomen, pelvis and chest, or hepatic MRI and CT scan (abdomen, pelvis and chest) without injection, if patient is allergic to CT contrast media).
- •No previous radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of metastatic disease.
- •Prior treatment with 5 FU or gemcitabine administered as a radiation sensitizer in the adjuvant setting is allowed, provided that at least 6 months have relapsed since completion of the last dose and no lingering toxicities are present.
- •Eastern Cooperative Oncology Group (ECOG) performance status of ≤
- •Males or females aged 18 to 75 years at the time of signing the Informed Consent Form (ICF).
- •Adequate blood function at baseline (obtained within 14 days before start of study treatment)
- •Adequate liver and renal function at baseline (obtained within 14 days before start of study treatment)
- •Patient has no clinical significant abnormalities in urinalysis results (obtained ≤ 14 days before start of study treatment)
Exclusion Criteria
- •Known brain metastases.
- •Patient has only locally advanced disease.
- •History of other malignancy in the last 5 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible. Patients with other malignancies are eligible if they were cured by surgery alone or surgery plus radiotherapy and have been continuously disease-free for at least 5 years.
- •Patients having received cytotoxic doses of any other chemotherapy (than 5FU and gemcitabine) in the adjuvant setting.
- •Peripheral sensory neuropathy ≥ grade 2 at the time of signing the ICF.
- •Active and uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
- •Known historical or active infection with HIV.
- •Major surgery, other than diagnostic surgery (i.e. surgery done to obtain a biopsy for diagnosis without removal of an organ), within 4 weeks prior to Day 1 of treatment in this study.
- •History of allergy or hypersensitivity to any of the study drugs or any of their excipients, or the patient exhibits any of the events outlined in the Contraindications or Special Warnings and Precautions sections of the SmPCs or Prescribing Information.
- •History of connective tissue disorders (e.g., lupus, scleroderma, arteritis nodosa).
Arms & Interventions
Gembrax followed by Folfirinox
Gembrax: Albumin-bound paclitaxel followed by Gemcitabine Day 1,8,15 followed by 2 weeks of rest Folfirinox: Oxaliplatin, irinotecan, leucovorin, 5FU bolus and continuous
Intervention: GEMBRAX
Gembrax followed by Folfirinox
Gembrax: Albumin-bound paclitaxel followed by Gemcitabine Day 1,8,15 followed by 2 weeks of rest Folfirinox: Oxaliplatin, irinotecan, leucovorin, 5FU bolus and continuous
Intervention: FOLFIRINOX
Outcomes
Primary Outcomes
Determination of the MTD
Time Frame: 18 months
Phase I: Identify the maximum tolerated dose and the recommended phase II dose of first line treatment combining gemcitabine plus nab-paclitaxel followed by folfirinox in metatstatic pancreatic adenocarcinoma. Phase II: Objective response rate of patients treated with this new combination
Secondary Outcomes
- Overall survival(12 months)