A Study of Perioperative Chemotherapy Plus Panitumumab in Patients With Colorectal Cancer Liver Metastases
Recruitment status was Recruiting
This is a phase II study to assess whether treatment with chemotherapy drugs FOLFOX (5-Fluorouracil (5FU), Oxaliplatin (Eloxatin) and Leucovorin (Folinic Acid)) or FOLFIRI (5-Fluorouracil (5FU), Irinotecan (Camptosar) and Leucovorin (Folinic Acid))and panitumumab before and after surgery can improve outcome in patients with liver metastases (the cancer has spread to other parts of the body such as the liver) that are resectable (can be surgically removed), from colorectal cancer that have a non mutant (wild-type) K-ras gene.
FOLFOX/FOLFIRI is an intravenous (given by vein) chemotherapy combination that is approved for colorectal cancer while panitumumab is also an intravenous drug and have been approved for treatment of refractory (not responding treatment) metastatic colorectal cancer whose cancers have the K-ras gene. These drugs are not approved for the treatment of colorectal cancer liver metastases (CRCLM) who can have surgery.
Patients will receive FOLFOX/FOLFIRI and panitumumab for four 2-week cycles before surgery. Surgery will be done no sooner than 4 weeks and no later than 8 weeks, after completion of the fourth cycle of chemotherapy.
If the liver metastases after the chemotherapy and surgery decreases or stops growing, then chemotherapy will be given after surgery. Treatments will start no sooner than 4 weeks, and no later than 12 weeks, after surgery. Patients will receive a maximum of 8 cycles of treatment with the combination of drugs and then receive panitumumab alone for a maximum of 12 cycles.
On treatment visits, patients will also have tests and procedures done. As part of the study, patients will provide archival tumor tissue and sample of tissue removed from surgery for K-ras testing. Patients will also be given the option of allowing the collected tissue for research (biomarker) studies and banking for future studies.
Drug: Panitumumab, Oxaliplatin, 5-FU
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of Perioperative Chemotherapy Plus Panitumumab in Patients With Colorectal Cancer Liver Metastases|
- To determine the 2 year disease-free survival rate in patients with resectable colorectal liver metastases treated with FOLFOX/FOLFIRI + panitumumab for 2 months pre-operatively and 4 months post-operatively, followed by panitumumab alone for 6 months. [ Time Frame: 2-years post-therapy ] [ Designated as safety issue: No ]
- To evaluate the objective response rate (ORR) to preoperative FOLFOX/FOLFIRI plus panitumumab (by RECIST criteria) in patients with wild type KRAS. [ Time Frame: until relapse ] [ Designated as safety issue: No ]
- To evaluate the pathologic complete response rate. [ Time Frame: until relapse ] [ Designated as safety issue: No ]
- To determine overall survival and toxicity. [ Time Frame: until death ] [ Designated as safety issue: Yes ]
- To explore correlative biomarkers of clinical response (EGFR, PTEN, MET, BRAF and PI3KCA). [ Time Frame: pre/post surgery ] [ Designated as safety issue: No ]
- To explore for correlation between available tissue from biopsy, primary tumor and metastatic lesion with regards to aforementioned pathologic biomarkers. [ Time Frame: pre/post surgery ] [ Designated as safety issue: No ]
- To determine the incidence of hepatocellular damage (fibrosis, steatosis) in normal liver tissue induced by preoperative chemotherapy. [ Time Frame: pre-surgery ] [ Designated as safety issue: Yes ]
|Study Start Date:||August 2010|
|Estimated Study Completion Date:||December 2014|
|Estimated Primary Completion Date:||December 2012 (Final data collection date for primary outcome measure)|
Drug: Panitumumab, Oxaliplatin, 5-FU
- Panitumumab 6 mg / kg, given over 60 minutes
- Oxaliplatin 85 mg / m2 combined with leucovorin 400 mg / m2, given over 2 hours OR
- Irinotecan 180 mg / m2 , given over 90 minutes, concurrent with leucovorin 400 mg / m2, given over 90 minutes
- 5FU 400 mg / m2, by bolus infusion
- 5FU 2400 mg / m2, given over 46 hours
Emerging data suggests that KRAS mutation is a strong predictor for resistance to EGFR antagonist therapy. In the KRAS wild-type cohort, the addition of EGFR antagonists to chemotherapy has been shown to improve RR and PFS. Improved response rate to neoadjuvant chemotherapy would be expected to improve surgical outcomes for patients with CRCLM. We therefore wish to test the hypothesis that the combination of FOLFOX/FOLFIRI and panitumumab, given perioperatively to patients with wild-type KRAS CRCLM will improve outcome, compared to historical control, in optimally resectable patients. As this patient population remains at high risk for recurrence post-chemotherapy, we also wish to explore the tolerability and efficacy of continued panitumumab monotherapy for an additional 6 months.
As opposed to most clinical trials for advanced colorectal cancer where the majority are treated with palliative intent, patients in this trial will all be treated aggressively with curative intent at the outset. There is also the additional benefit of assessment of tumor tissue after treatment with a biologic agent.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01260415
|Contact: Stephen Welch, MDfirstname.lastname@example.org|
|London Regional Cancer Centre||Recruiting|
|London, Ontario, Canada|
|Contact: Stephen Welch, MD 416-685-8640 email@example.com|
|The Ottawa Hospital Cancer Center||Recruiting|
|Ottawa, Ontario, Canada|
|Contact: Tim Asmis, MD 613-737-7700 ext 79556 firstname.lastname@example.org|
|Mount Sinai Hospital||Recruiting|
|Toronto, Ontario, Canada|
|Contact: Ronald Burkes, MD 416-586-5117 email@example.com|
|Princess Margaret Hospital||Recruiting|
|Toronto, Ontario, Canada|
|Contact: Malcolm J Moore, MD 416-946-2263 firstname.lastname@example.org|
|Contact: Chantale Blattler 416-946-4501 ext 3692 email@example.com|
|Study Chair:||Stephen Welch, MD||London Regional Cancer Center|
|Principal Investigator:||Sean Cleary, MD||Toronto General Hospital|