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

• Conditions: metastatic colorectal carcinoma; MedDRA version: 9.1Level: LLTClassification code 10010036Term: Colorectal carcinoma; MedDRA version: 9.1Level: LLTClassification code 10027477Term: Metastatic carcinoma

• Registration Number: EUCTR2007-001116-22-SE
• Lead Sponsor: Merck Sharp & Dohme (Sweden) AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-10-30
• Last Update Posted: 11 September 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 1100

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 ß-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)
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
;
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 ß-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)
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.
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.
;
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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified