A Phase II/III Study of MK-0646 Treatment in Combination with Cetuximab and Irinotecan for Patients with Metastatic Colorectal Cancer

Phase 1

Conditions: metastatic colorectal carcinoma
MedDRA version: 9.1 Level: LLT Classification code 10010036 Term: Colorectal carcinoma
MedDRA version: 9.1 Level: LLT Classification code 10027477 Term: Metastatic carcinoma

Registration Number: EUCTR2007-001116-22-GB

Lead Sponsor: Merck Sharp & Dohme Corp.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 1168

Inclusion Criteria

1.Patient has histologically or cytologically confirmed colorectal cancer.
2.Patient has at least one measurable lesion greater than or equal to 15 mm.
3.Patient has previously failed both irinotecan and oxaliplatin containing regimens and should have progressed on or within 3 months of completing their last line of therapy with objective radiological evidence of progression as verified by previous radiologic scans. Note: Failing oxaliplatin would include failure due to toxicities.
4.Patient is male or female, and =18 years of age on the day of signing informed consent.
5.Patient has performance status 0-1 on the ECOG Performance Scale.
6.Patient has adequate organ function as indicated by the following laboratory values:

Absolute Neutrophil Count (ANC) =1,500/mcL

Platelets =100,000/mcL

Hemoglobin =9 g/dL-without qualifications, use of erythropoietin and transfusions are allowed

Serum Creatinine/calculated creatine clearance =2 times the upper limit of normal (ULN)/ =60 mL/min (patients with creatinine levels =2 times the ULN). Patient may not be on dialysis. (Creatinine clearance should be calculated per institutional standard.)

Serum total bilirubin=1.5 times the ULN

AST (SGOT) and ALT (SGPT) =5 times the ULN

Prothrombin time (PT) =1.2 times the ULN

Partial Thromboplastin time (PTT) =1.2 times the ULN

7. Patient has archival tumor available for analysis for biomarker studies.

8. Patient has a wtKRAS metastatic colorectal cancer determined by (1) testing at the
program central laboratory during the screening period as outlined in the MK0646-
004 Assay Charter; or (2) a documented history that the colorectal cancer was
determined to be ’wtKRAS’ by a test conducted at a local laboratory in the period
between first diagnosis and consideration for enrollment in the study (see section
3.1.4.1.1)

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Patient who has had chemotherapy, radiotherapy, or biological therapy within 2 weeks prior to initial dosing on this study or whose toxicities from agents administered 2 weeks earlier have not resolved to at least grade 1 or baseline, or who is within 3 weeks from a prior study.
2.Patient is currently participating or has participated in a study with an investigational compound or device within 30 days or 5 half-lives of the investigational agent, whichever is longer, of initial dosing on this study.
3.Patient has experienced intolerable toxicity to irinotecan therapy.
4.Patient has prior exposure to IGF-1R inhibitors or EGFR inhibitors (e.g. cetuximab).
5.Patient has known CNS metastases and/or carcinomatous meningitis.
6.Patient has primary central nervous system tumor.
7.Patient has a known hypersensitivity to the components of study drugs or its analogs that is not treatable by premedication with antihistamines and steroids.
8.Patient has a history or current evidence of any condition, therapy, or lab abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate.
9.Patient with a history of a prior malignancy with the exception of cervical intraepithelial neoplasia; basal cell carcinoma of the skin; adequately treated localized prostate carcinoma with PSA <1.0; who has undergone potentially curative therapy with no evidence of that disease for five years, or who is deemed at low risk for recurrence by his/her treating physician.
10.Patient is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study.
11.Patient is known to be Human Immunodeficiency Virus (HIV)-positive.
12.Patient has known active Hepatitis B or C.
13.Patient has symptomatic ascites or pleural effusion. A patient who is clinically stable following treatment for these conditions is eligible.
14.Patient is concurrently using growth hormone (GH), or growth hormone inhibitors.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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