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

NCT00655499 | Completed Phase 2 Results

• 5 other identifiers: CDR0000593012GERCOR-PIMABI-C07-12007-004806-28EU-20836AMGEN-GERCOR-PIMABI-C07-1
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 9

Brief Summary

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.

Conditions

Colorectal Cancer

Keywords

adenocarcinoma of the colon; adenocarcinoma of the rectum; stage IV colon cancer; recurrent rectal cancer; stage IV rectal cancer; recurrent colon cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) During the Combination Therapy Phase

  Per the modified Response Evaluation Criteria in Solid Tumors (m-RECIST) for target lesions and radiogically assessed (CT Scans; optionally MRI): Complete Response (CR; Disappearance of all target lesions) or Partial Response (PR; At least a 30% decrease in the sum of the LD of target lesions) during the combination therapy phase.Overall Response (OR) = CR + PR.

  Up to 20 months

Secondary Outcomes (3)

• Disease Control Rate (DCR)

  Up to 20 months

• Progression-free Survival (PFS)

  Up to 20 months

• Overall Survival (OS)

  Up to 20 months

Study Arms (1)

Panitumumab + CPT11 (irinotecan hydrochloride)

EXPERIMENTAL

1 cycle every 14 days (J1= J15)

Drug: Panitumumab; Drug: Irinotecan hydrochloride; Genetic: Chromogenic in situ hybridization; Genetic: Fluorescence in situ hybridization; Genetic: Gene expression analysis; Other: Laboratory biomarker analysis

Interventions

Panitumumab DRUG

6 mg/kg

Also known as: Vectibix

Panitumumab + CPT11 (irinotecan hydrochloride)

Irinotecan hydrochloride DRUG

180 mg/kg

Also known as: Camptosar

Panitumumab + CPT11 (irinotecan hydrochloride)

Chromogenic in situ hybridization GENETIC

Panitumumab + CPT11 (irinotecan hydrochloride)

Fluorescence in situ hybridization GENETIC

Panitumumab + CPT11 (irinotecan hydrochloride)

Gene expression analysis GENETIC

Panitumumab + CPT11 (irinotecan hydrochloride)

Laboratory biomarker analysis OTHER

Panitumumab + CPT11 (irinotecan hydrochloride)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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 fluoropyrimidines (i.e., fluorouracil/folinic acid or capecitabine) with or without bevacizumab, and irinotecan hydrochloride alone or in combination with fluoropyrimidines (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 St. John's wort (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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• GERCOR - Multidisciplinary Oncology Cooperative Group: lead

Study Sites (9)

Centre Paul Papin

Angers, 49036, France

Location

Hopital Prive Jean Mermoz

Lyon, 69008, France

Location

Hopital Clinique Claude Bernard

Metz, 57072, France

Location

Centre Hospitalier Intercommunal Le Raincy - Montfermeil

Montfermeil, 93370, France

Location

Hopital Pitie-Salpetriere

Paris, 75013, France

Location

Hopital Bichat - Claude Bernard

Paris, 75018, France

Location

Hopital Saint Antoine

Paris, 75571, France

Location

Hopital Tenon

Paris, 75970, France

Location

Hopital Foch

Suresnes, 92151, France

Location

Related Publications (1)

• Andre T, Blons H, Mabro M, Chibaudel B, Bachet JB, Tournigand C, Bennamoun M, Artru P, Nguyen S, Ebenezer C, Aissat N, Cayre A, Penault-Llorca F, Laurent-Puig P, de Gramont A; GERCOR. Panitumumab combined with irinotecan for patients with KRAS wild-type metastatic colorectal cancer refractory to standard chemotherapy: a GERCOR efficacy, tolerance, and translational molecular study. Ann Oncol. 2013 Feb;24(2):412-419. doi: 10.1093/annonc/mds465. Epub 2012 Oct 5.

  PMID: 23041588 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms; Rectal Neoplasms

Interventions

Panitumumab; Irinotecan; In Situ Hybridization; In Situ Hybridization, Fluorescence; Gene Expression Profiling

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; Camptothecin; Alkaloids; Heterocyclic Compounds; Staining and Labeling; Histocytological Preparation Techniques; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Investigative Techniques; Nucleic Acid Hybridization; Genetic Techniques; Cytogenetic Analysis

Results Point of Contact

• Title: Regulatory affairs
• Organization: GERCOR

Regulatory.Affairs@gercor.com.fr

00331 40 29 85 00

Study Officials

• Thierry Andre, MD

  GERCOR - Multidisciplinary Oncology Cooperative Group

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: April 9, 2008
• First Posted: April 10, 2008
• Study Start: June 1, 2008
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2012
• Last Updated: September 21, 2021
• Results First Posted: September 21, 2021

Record last verified: 2016-08

Locations

FR (9)