Clinical trial NCT00077233 (phase 3, status: terminated)
Conditions: colorectal cancer
ICD codes: C05.2, C10.0, C16.0, C16.4, C17.0, C17.1, C17.2
Drugs: cetuximab, 5-fu, irinotecan, leucovorin, oxaliplatin
SMILES: [H][C@]12SCC(COC(C)=O)=C(N1C(=O)[C@H]2NC(=O)C(=N/OC)\C1=CSC(N)=N1)C(O)=O, [H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1, CC[C@@]1(O)C(=O)OCC2=C1C=C1N(CC3=CC4=CC=CC=C4N=C13)C2=O, [H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1, [H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1
Reason stopped: 
    poor accrual
  
Eligibility criteria:

        1. Locally Advanced or Metastatic Colorectal Cancer

               -  Eligible patients must have histologically or cytologically documented locally
                  advanced or metastatic colorectal cancer. The site of the primary lesion must be
                  or have been confirmed endoscopically, surgically or radiologically to have been
                  in the large bowel.

               -  Patients with a history of colorectal cancer treatment by surgical resection who
                  develop radiological or clinical evidence of metastatic cancer do not require
                  separate histological or cytological confirmation of metastatic disease unless:

                    -  Either an interval of greater than five years has elapsed between the
                       primary surgery and the development of metastatic disease OR

                    -  The primary cancer was stage I.

               -  Clinicians should consider biopsy of lesions to establish the diagnosis of
                  metastatic colorectal cancer in each case if there is substantial clinical
                  ambiguity regarding the nature or source of apparent metastases.

          2. No prior treatment for advanced or metastatic colorectal cancer

               -  Patients may have received prior adjuvant chemotherapy (no more than 6 months or
                  4 cycles) or radiation with radiosensitizing chemotherapy. The last course of
                  chemotherapy must have concluded > 12 months prior to registration. Patients may
                  not have previously received irinotecan ≤ or oxaliplatin therapy in either the
                  adjuvant or metastatic setting. No concurrent use of additional investigational
                  agents is allowed while participating in this study.

          3. Patients may not have had prior radiotherapy to greater than 25% of bone marrow.

             Standard adjuvant rectal cancer chemoradiation will not exclude the patient from
             protocol entry. Radiation must have concluded ≥ 4 weeks from registration.

          4. Patients should have completed any major surgery ≥ 4 weeks from registration. Patients
             must have completed any minor surgery ≥ 2 weeks from registration. Patients must have
             fully recovered from the procedure. Insertion of a vascular access device is not
             considered major or minor surgery.

          5. No previous or concurrent malignancy is allowed except for adequately treated basal
             cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which
             the patient has been disease-free for five years.

          6. Age ≥ 18 years

          7. CTC (ECOG) performance status of 0-1.

          8. No evidence of Gilbert's syndrome - Patients with Gilbert's Syndrome may have a
             greater risk of irinotecan toxicity due to the abnormal glucuronidation of SN-38.
             Evidence of Gilbert's Syndrome would include a prior finding of an isolated elevation
             of indirect bilirubin.

          9. Patients must have at least one paraffin block available or appropriate number of
             unstained slides for analysis of EGFR status.

         10. No symptomatic sensory peripheral neuropathy of ≥ grade II at baseline.

         11. Non-pregnant and non-lactating

               -  Women of child bearing potential (WOCBP) must have a negative serum or urine
                  pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG within 72
                  hours prior to initiation of treatment. This is because DNA alkylating agents are
                  known to be teratogenic, and the effects of irinotecan, OXAL, 5-FU and C225 on a
                  developing fetus at the recommended therapeutic doses are unknown.

               -  Women of child bearing potential includes:

                    -  any female who has experienced menarche and who has not undergone surgical
                       sterilization (hysterectomy, bilateral tubal ligation or bilateral
                       oophorectomy) or

                    -  is not postmenopausal [defined as amenorrhea ≥ 12 consecutive months] or

                    -  women on hormone replacement therapy [HRT] with documented serum follicle
                       stimulating hormone (FSH) level > 35 mIU/mL

                    -  women who are using oral, implanted or injectable contraceptive hormones or
                       mechanical products such as an intrauterine device or barrier methods
                       (diaphragm, condoms, spermicides) to prevent pregnancy or practicing
                       abstinence or where partner is sterile (eg, vasectomy), should be considered
                       to be of child bearing potential.

               -  Should a woman become pregnant or suspect she is pregnant while participating on
                  on this study, she should inform her physician immediately. Because the risk of
                  toxicity of these agents in nursing infants is also unknown, breastfeeding should
                  be discontinued.

         12. No known central nervous system metastases or carcinomatous meningitis.

         13. No interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the
             lung.

         14. No pleural effusion or ascites that causes ≥ grade 2 dyspnea.

         15. No predisposing colonic or small bowel disorders in which the symptoms are
             uncontrolled as indicated by baseline pattern of > 3 watery or soft stools daily in
             patients without a colostomy or ileostomy. Patients with a colostomy or ileostomy may
             be entered at investigator discretion.

         16. No prior exposure or known sensitivity to chimerized or murine antibodies, C225 (or
             other EGFR inhibitors) or any tyrosine kinase inhibitors

         17. No significant history of cardiac disease, such as unstable angina, CHF, MI, stroke or
             a LVEF below the institutional range of normal on a baseline multiple gated
             acquisition (MUGA) or echocardiogram.

         18. Patients must not have an uncontrolled seizure disorder, or active neurological
             disease.

         19. Patients may not have received itraconazole or ketoconazole less than 4 weeks prior to
             registration.

         20. Required Initial Laboratory Values:

               -  Granulocytes ≥ 1500/ µl

               -  Hemoglobin ≥ 9.0 gram/dL (patient may be transfused to meet this criterion)

               -  Platelet count ≥ 100,000/ µl

               -  Creatinine ≤ 1.5 x Upper limits of normal (ULN)

               -  Bilirubin ≤ 1.5 mg/dL

               -  AST ≤ 5.0 x ULN

               -  Albumin ≥ 2.5 gram/dL