E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
metastatic colorectal carcinoma |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10010036 |
E.1.2 | Term | Colorectal carcinoma |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027477 |
E.1.2 | Term | Metastatic carcinoma |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1. To determine overall survival of patients with metastatic colorectal cancer expressing the wtKRAS genotype treated with the combination of MK-0646, cetuximab, and irinotecan compared to patients treated with cetuximab and irinotecan alone. 2. To evaluate progression-free survival of patients with metastatic colorectal cancer expressing the wtKRAS genotype treated with the combination of MK-0646, cetuximab, and irinotecan compared to patients treated with cetuximab and irinotecan alone. 3. To assess the safety profile of MK-0646 in combination with cetuximab and irinotecan. |
|
E.2.2 | Secondary objectives of the trial |
1. To evaluate the objective response rate of patients with metastatic colorectal cancer expressing the wtKRAS genotype treated with the combination of MK-0646, cetuximab and irinotecan compared to patients treated with cetuximab and irinotecan alone. 2. To evaluate progression-free survival of patients with metastatic colorectal cancer enrolled prior to Amendment 04 treated with the combination of MK-0646, cetuximab, and irinotecan compared to patients treated with cetuximab and irinotecan alone. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 (System / Laboratory Value): ¤Hematological -Absolute Neutrophil Count (ANC): ≥1,500/mcL -Platelets: ≥100,000/mcL -Hemoglobin: ≥9 g/dL-without qualifications, use of erythropoietin and transfusions are allowed ¤Renal -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. ¤Hepatic -Serum total bilirubin: ≤1.5 times the ULN -AST (SGOT) and ALT (SGPT): ≤5 times the ULN ¤Coagulation -Prothrombin time (PT): ≤1.2 times the ULN -Partial Thromboplastin time (PTT): ≤1.2 times the ULN *)Creatinine clearance should be calculated per institutional standard.
7. Female patient of childbearing potential has a negative serum or urine β-hCG pregnancy test at baseline. 8. Patient, or patient’s legal representative, has voluntarily agreed to participate by giving written informed consent. 9. Patient has archival (recent or remote) tumor available for analysis for biomarker studies. 10. 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) |
|
E.4 | Principal 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. 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 has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 11. Patient is, at the time of signing informed consent, a regular user (including recreational use) of any illicit drugs or had a recent history (within the last year) of drug or alcohol abuse. 12. Patient is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study. 13. Patient is known to be Human Immunodeficiency Virus (HIV)-positive. 14. Patient has known active Hepatitis B or C. 15. Patient has symptomatic ascites or pleural effusion. A patient who is clinically stable following treatment for these conditions is eligible. 16. Patient is concurrently using growth hormone (GH), or growth hormone inhibitors. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary clinical endpoints will be PFS and OS. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Yes |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 7 |