A Study of Perioperative Chemotherapy Plus Panitumumab in Patients With Colorectal Cancer Liver Metastases

NCT01260415 | Completed Phase 2 DMC

• 1 other identifier: PMH DDP - CRCLM1
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Colorectal Cancer; Liver Metastases

Keywords

colorectal cancer; liver metastases; panitumumab; FOLFOX; Colorectal cancer with liver metastases

Outcome Measures

Primary Outcomes (1)

• 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.

  2-years post-therapy

Secondary Outcomes (6)

• To evaluate the objective response rate (ORR) to preoperative FOLFOX/FOLFIRI plus panitumumab (by RECIST criteria) in patients with wild type KRAS.

  until relapse

• To evaluate the pathologic complete response rate.

  until relapse

• To determine overall survival and toxicity.

  until death

• To explore correlative biomarkers of clinical response (EGFR, PTEN, MET, BRAF and PI3KCA).

  pre/post surgery

• To explore for correlation between available tissue from biopsy, primary tumor and metastatic lesion with regards to aforementioned pathologic biomarkers.

  pre/post surgery

Study Arms (1)

Folfox/Folfiri, Panitumumab

EXPERIMENTAL

Eligible patients will recieved chemotherapy/panitumumab for 2 months (4 cycles) pre-operatively and 4 months post-operatively, plus a further 6 months of pantimumab post-chemotherapy

Drug: Panitumumab, Oxaliplatin, 5-FU

Interventions

Panitumumab, Oxaliplatin, 5-FU DRUG

* 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

Folfox/Folfiri, Panitumumab

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically or cytologically confirmed colorectal cancer with available tissue to test for K-RAS mutation. Biopsy is required if no archived tissue is available. K-RAS mutation status must be confirmed prior to registration. Only patients with K-RAS wild-type cancers are eligible.
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>20 mm with conventional techniques or as \>10 mm with spiral CT scan.
• Patients must have resectable hepatic colorectal metastases.
• Patients may have synchronous unresected primary disease upon registration. Primary must be resectable, either at same laparotomy or at separate laparotomy from liver resection.
• Age \>18 years.
• Patients must have Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
• Patients must have normal organ and marrow function as defined below:
• leukocytes \> 3,000/mcL absolute neutrophil count \>1,500/mcL platelets \>100,000/mcL hemoglobin \> 90 g/L total bilirubin \< 2 x upper limit of normal (\< 1.5 x ULN for FOLFIRI), AST(SGOT) and ALT(SGPT)\< 5 x upper limit of normal (\< 3 x ULN for FOLFIRI);creatinine within normal institutional limits OR- creatinine clearance \>50 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
• Appropriate imaging investigations, including CT or MRI of chest/abdomen/pelvis. Other scans if clinically indicated may be performed. All imaging studies must be performed within 28 days of study entry.
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study and for a period of six months after cessation of study therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Patients must have had no previous systemic treatment in the adjuvant or metastatic setting within 6 months of registration.
• Patients may not have had prior treatment with an EGFR antagonist.
• Patients may not have a history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid malignancies curatively treated with no evidence of disease for ≥ 5 years.
• Patients may not have extrahepatic metastatic disease. Patients who have had prior surgical resection for hepatic metastases or extrahepatic disease (eg. pulmonary metastases) are also excluded from this study.
• Patients may not have pre-existing chronic hepatic disease (eg. cirrhosis, chronic active hepatitis B or C)
• History of allergic reactions, or intolerance, attributed to compounds of similar chemical or biologic composition to 5-fluorouracil, oxaliplatin, or panitumumab.
• Patients being considered for irinotecan must not have a history of Gilbert's syndrome.
• Patients may not have uncontrolled inter-current illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.
• HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with the agents used in this study. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.
• Patients with active cardiovascular disease, i.e., unstable angina, New York Heart Association grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medications, or grade II or greater peripheral vascular disease. In addition, patients with arterial or venous thrombosis, myocardial infarction, and cerebral vascular accidents (stroke / transient ischemic attach (TIA)) within 6 months prior to study entry will be excluded.
• Patients with a history of interstitial pneumonitis or pulmonary fibrosis will be excluded.
• Organ allografts requiring immunosuppressive therapy.

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (4)

London Regional Cancer Centre

London, Ontario, Canada

Location

The Ottawa Hospital Cancer Center

Ottawa, Ontario, Canada

Location

Mount Sinai Hospital

Toronto, Ontario, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, Canada

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Panitumumab; Oxaliplatin; Fluorouracil

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Stephen Welch, MD

  London Regional Cancer Center

  STUDY CHAIR

• Sean Cleary, MD

  Toronto General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2010
• First Posted: December 15, 2010
• Study Start: August 1, 2010
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: May 14, 2019

Record last verified: 2019-05

Locations

CA (4)