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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]

Phase 2
18 Years
80 Years
Not Enrolling
Colorectal Cancer

Thank you

Trial Information

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]



- 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.


- 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.


- 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

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

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

Inclusion Criteria


- 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


- 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


- 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

- Concurrent elective surgery allowed in patients eligible for surgical resection of
metastases as curative therapy

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Objective response rate (ORR; radiologically confirmed complete response [CR] or partial response [PR]) during the combination therapy phase

Safety Issue:


Principal Investigator

Thierry Andre, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR)


France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Study ID:




Start Date:

June 2008

Completion Date:

June 2012

Related Keywords:

  • Colorectal Cancer
  • adenocarcinoma of the colon
  • adenocarcinoma of the rectum
  • stage IV colon cancer
  • recurrent rectal cancer
  • stage IV rectal cancer
  • recurrent colon cancer
  • Colorectal Neoplasms