Panitumumab and Irinotecan as Third-Line Therapy in Treating Patients With Metastatic Colorectal Cancer

This study has been completed.
Sponsor:
Information provided by:
Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR)
ClinicalTrials.gov Identifier:
NCT00655499
First received: April 9, 2008
Last updated: August 22, 2012
Last verified: August 2012
  Purpose

RATIONALE: Monoclonal antibodies, such as panitumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving panitumumab together with irinotecan may kill more tumor cells.

PURPOSE: This phase II clinical trial is studying giving panitumumab together with irinotecan to see how well it works as third-line therapy in treating patients with metastatic colorectal cancer.


Condition Intervention Phase
Colorectal Cancer
Biological: panitumumab
Drug: irinotecan hydrochloride
Genetic: chromogenic in situ hybridization
Genetic: fluorescence in situ hybridization
Genetic: gene expression analysis
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label Phase II Clinical Trial of Panitumumab in Combination With Irinotecan for Patients With Advanced Metastatic Colorectal Cancer Without KRAS Mutation (Wild Type) in Third Line Chemotherapy (Patients Pretreated With FOLFOX or XELOX ± Bevacizumab and Irinotecan Alone or FOLFIRI or CAPIRI ± Bevacizumab) [PIMABI]

Resource links provided by NLM:


Further study details as provided by Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR):

Primary Outcome Measures:
  • Objective response rate (ORR; radiologically confirmed complete response [CR] or partial response [PR]) during the combination therapy phase [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • ORR during the entire treatment phase (i.e., combination therapy and monotherapy) [ Designated as safety issue: No ]
  • Disease control rate (DCR) [ Designated as safety issue: No ]
  • Duration of response [ Designated as safety issue: No ]
  • Time to response [ Designated as safety issue: No ]
  • Progression-free survival time [ Designated as safety issue: No ]
  • Time to progression [ Designated as safety issue: No ]
  • Duration of stable disease [ Designated as safety issue: No ]
  • Time to treatment failure [ Designated as safety issue: No ]
  • Correlation between KRAS and KRAF mutations, EGFR gene copy number, and ORR and DCR [ Designated as safety issue: No ]
  • Incidence and severity of adverse events [ Designated as safety issue: Yes ]
  • Changes in laboratory values [ Designated as safety issue: Yes ]
  • Change in vital signs [ Designated as safety issue: Yes ]
  • Investigational medicinal product compliance [ Designated as safety issue: Yes ]
  • Incidence of dose adjustments [ Designated as safety issue: Yes ]
  • Incidence of concurrent medications [ Designated as safety issue: Yes ]
  • Changes from baseline over time in WHO performance status [ Designated as safety issue: Yes ]
  • Biomarkers (EGFR amplification status by chromogenic in situ hybridization and FISH, KRAS and KRAF mutations, and STAT3 expression [ Designated as safety issue: No ]

Estimated Enrollment: 68
Study Start Date: June 2008
Study Completion Date: June 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • To assess the objective response rate when panitumumab is administered in combination with irinotecan hydrochloride as third-line therapy in patients with advanced metastatic colorectal cancer without KRAS mutation (wild type) previously treated with FOLFOX or XELOX chemotherapy with or without bevacizumab and irinotecan hydrochloride alone or FOLFIRI or CAPIRI chemotherapy with or without bevacizumab.

Secondary

  • To assess the efficacy in terms of disease control rate, duration of response, time to response, progression-free survival, time to progression, time to treatment failure, and duration of stable disease.
  • To assess the efficacy and safety of this regimen, followed by panitumumab alone in patients who discontinue third-line irinotecan hydrochloride due to toxicity.

Tertiary

  • To correlate this regimen with EGFR expression, detection of the functional genetic polymorphisms of the EGFR gene, EGFR gene amplification (FISH), EGFR activation detection, EGFR downstream protein and gene expression parameters, proteomics, and epigenetics.

OUTLINE: This is a multicenter study.

Patients receive panitumumab IV over 30-90 minutes and irinotecan hydrochloride IV over 90 minutes on day 1. Patients who discontinue irinotecan hydrochloride may receive panitumumab monotherapy. Courses repeat every 14 days in the absence of disease progression and unacceptable toxicity.

Archived tumor tissue specimens are obtained at baseline for correlative laboratory studies. Tissue samples are analyzed for EGFR amplification status by chromogenic in situ hybridization and fluorescence in situ hybridization, KRAS and KRAF mutations, and STAT3 expression.

After completion of study therapy, patients are followed at approximately 56 days.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed colorectal adenocarcinoma

    • Metastatic disease
  • Wild type KRAS (no mutation) by allelic discrimination on tumor DNA
  • Measurable disease (≥ 10 mm) per modified RECIST criteria
  • Previously treated for metastatic disease with oxaliplatin and fluorpyrimidines (i.e., fluorouracil/folinic acid or capecitabine) with or without bevacizumab, and irinotecan hydrochloride alone or in combination with fluorpyrimidines (i.e., fluorouracil/folinic acid or capecitabine) with or without bevacizumab
  • Must have paraffin-embedded tissue or unstained tumor slides from primary or metastatic tumor available for correlative studies
  • Must be registered with a national health care system (CMU included)
  • No CNS metastases unless previously treated or asymptomatic, provided patient has been off steroids for at least 30 days prior to study treatment

PATIENT CHARACTERISTICS:

  • WHO performance status of 0-2
  • ANC ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 9 g/dL
  • Creatinine < 150 μmol/L or creatinine clearance > 30 mL/min
  • AST ≤ 3 times upper limit of normal (ULN) (5 times ULN if liver metastases present)
  • ALT ≤ 3 times ULN (5 times ULN if liver metastases present)
  • Bilirubin ≤ 1.5 times ULN
  • Magnesium normal
  • No significant cardiovascular disease, including unstable angina or myocardial infarction within the past 6 months
  • No history of treated or untreated ventricular arrhythmia
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective double barrier contraception during and for 6 months after completion of study treatment
  • No other malignant tumors within the past five years except basocellular carcinoma, in situ cancer of the cervix or uterus, or any UDAW cancers for which there has been complete resection for at least three years
  • No known hypersensitivity to an excipient (vehicle) of panitumumab or known hypersensitivity of irinotecan trihydrate chlorhydrate or known hypersensitivity excipient (vehicle) of irinotecan hydrochloride
  • No history of interstitial pneumonitis, pulmonary fibrosis or evidence of interstitial pneumonitis, or pulmonary fibrosis on baseline chest CT scan
  • No active inflammatory bowel disease, other bowel disease causing chronic diarrhea (defined as > 4 loose stools per day), or bowel occlusion
  • No history of Gilbert syndrome
  • No history of any medical condition that may increase the risks associated with study participation or may interfere with the interpretation of the study results
  • No known positive test for HIV infection, hepatitis C virus, chronic active hepatitis B infection
  • No comorbid disease that would increase risk of toxicity
  • No disorder that would compromise the patient's ability to give written informed consent and/or comply with study procedures
  • Must be willing and able to comply with study requirements
  • No grade IV toxicity associated with a past treatment with irinotecan hydrochloride

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • At least 14 days since prior treatment for systemic infection
  • No prior or concurrent anti-EGFR antibody therapy (e.g., cetuximab) or treatment with small molecule EGFR tyrosine kinase inhibitors (e.g., erlotinib hydrochloride)

    • Patients who discontinued their first dose of anti-EGFR therapy (i.e., cetuximab) because of an infusion reaction are eligible
  • More than 30 days since prior and no other concurrent investigational agent (no delay for non-investigational treatment)
  • More than 14 days since prior CYP3A4 enzyme, including anticonvulsant medication (e.g., phenytoin, phenobarbital, or carbamazepine)
  • More than 14 days since prior rifampicin
  • More than 14 days since prior radiotherapy and recovered
  • More than 7 days since prior and no concurrent ketoconazole
  • More than 28 days since prior and no concurrent major surgical procedure
  • Concurrent topical, oral, or IV antibiotics used to treat skin- or nail-related toxicities are allowed at the investigator's discretion
  • No other concurrent experimental or approved anti-tumor therapies (e.g., bevacizumab), chemotherapy other than irinotecan hydrochloride, non-palliative radiotherapy, or systemic steroids (except when used for symptomatic skin- or nail-related toxicities requiring withholding of the panitumumab dose, as chemotherapy premedication, or for an infusion reaction)
  • No concurrent millepertuis (i.e., Hypericum perforatum)
  • No concurrent phenobarbital, clarithromycin, erythromycin, HIV protease inhibitors, cyclosporine or tacrolimus, or nefazodone
  • Concurrent minor surgery, procedures, or surgery arising as needed or necessary allowed
  • Concurrent elective surgery allowed in patients eligible for surgical resection of metastases as curative therapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00655499

Locations
France
Centre Paul Papin
Angers, France, 49036
Hopital Prive Jean Mermoz
Lyon, France, 69008
Hopital Clinique Claude Bernard
Metz, France, 57072
Centre Hospitalier Intercommunal Le Raincy - Montfermeil
Montfermeil, France, 93370
Hopital Saint Antoine
Paris, France, 75571
Hopital Pitie-Salpetriere
Paris, France, 75013
Hopital Bichat - Claude Bernard
Paris, France, 75018
Hopital Tenon
Paris, France, 75970
Hopital Foch
Suresnes, France, 92151
Sponsors and Collaborators
Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR)
Investigators
Principal Investigator: Thierry Andre, MD Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR)
  More Information

Additional Information:
No publications provided by Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00655499     History of Changes
Other Study ID Numbers: CDR0000593012, GERCOR-PIMABI-C07-1, EUDRACT 2007-004806-28, EU-20836, AMGEN-GERCOR-PIMABI-C07-1
Study First Received: April 9, 2008
Last Updated: August 22, 2012
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: Committee for the Protection of Personnes

Keywords provided by Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR):
adenocarcinoma of the colon
adenocarcinoma of the rectum
stage IV colon cancer
recurrent rectal cancer
stage IV rectal cancer
recurrent colon cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Irinotecan
Camptothecin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 16, 2014