Panitumumab and Irinotecan as Third-Line Therapy in Treating Patients With Metastatic Colorectal Cancer
Condition: Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Intervention: Panitumumab; Irinotecan hydrochloride; Chromogenic in situ hybridization; Fluorescence in situ hybridization; Gene expression analysis; Laboratory biomarker analysis
Intervention description: 6 mg/kg; 180 mg/kg
Intervention MeSH terms: Irinotecan; Panitumumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 65.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: adenocarcinoma of the colon; adenocarcinoma of the rectum; stage IV colon cancer; recurrent rectal cancer; stage IV rectal cancer; recurrent colon cancer

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.
    

Eligibility 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 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