Clinical trial NCT00792363: Irinotecan and Panitumumab as 3rd Line Treatment for mCRC Without KRAS Mutations
Official title: A Phase II Study of Irinotecan and Panitumumab as 3rd Line Treatment of Patients With Metastatic Colorectal Cancer Without KRAS Mutations
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Keywords: KRAS
Lead sponsor: Vejle Hospital
Sponsor class: OTHER
First posted: 2008-11-17
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to investigate the effect and the side effect profile of irinotecan and panitumumab administered every 3 weeks as 3rd line treatment for patients with metastatic colorectal cancer without KRAS mutations.

Detailed description: Colorectal cancer is one of the most frequent types of cancer in Denmark with approximately 3,400 diagnosed patients per year. The prognosis for these patients is still very poor and more than half of them will develop metastatic disease and thus be candidates for chemotherapy.

In Denmark 5-FU and Oxaliplatin or Irinotecan has been used for several years either as combination or mono therapy. In recent years biological antibodies targeted against EGFR have been added to this treatment. A newly developed antibody is Panitumumab, which enables treatment every 3 weeks instead of weekly administration.

The effect of EGFR activation is mediated through intracellular pathways involving the KRAS protein. It has been proven that a mutation of KRAS causes the KRAS protein to be constantly activated, and patients with these mutations do not benefit from antibodies against EGFR. Approximately 40% of the patients present these mutations.

Eligibility criteria: Inclusion Criteria:

* Histologically verified adenocarcinoma in colon or rectum with metastatic spread.
* No mutations in the KRAS gene.
* Resistance to 5-FU, oxaliplatin and irinotecan.
* Age ≥18 years.
* PS 0-2.
* Measurable disease according to RECIST criteria.
* Haematology: Neutrophilocytes ≥1.5 x 109/l, leukocytes ≥3.0 x 109/l, thrombocytes ≥100 and bilirubinaemia ≤3 x upper normal value. Samples no more than 4 weeks old.
* Fertile women must present a negative pregnancy test and use secure birth control during and 3 months after treatment.
* Acceptance that blod and tissue samples are kept for subsequent investigation of biomarkers.
* Oral and written informed consent.

Exclusion Criteria:

* Other malignant disease within the past 5 years, excl. non-melanoma skin cancer and carcinoma in situ cervicis uteri.
* Chemotherapy, radiotherapy or immunotherapy within the past 4 weeks.
* Verified or clinically suspected CNS metastasis.
* Other experimental treatment.
* Serious medical disease according to investigator's judgement.
* Pregnant or breastfeeding women.
* Hypersensitivity to the active substance or to one or more of the auxiliary substances.
* Patients with interstitial pneumonitis or pulmonary fibrosis.

Primary outcomes:
measure: Response Rate
timeFrame: Every 9 weeks. Up to 6 months
Secondary outcomes:
measure: Overall survival
timeFrame: 6 months
measure: Progression free survival
timeFrame: 6 months
Other outcomes:
Locations:
city: Vejle
country: Denmark
facility: Vejle Hospital, Dept. of Oncology
Study officials:
affiliation: Vejle Hospital
name: Anders Jakobsen, Professor
role: STUDY_CHAIR
References: