A trial for people who have colorectal cancer, a certain type of protein and received previous therapy for that cancer will be treated with 2 medications plus the investigational drug or placebo.
- Conditions
- Treatment for metastatic colorectal cancer (CRC) in combination with irinotecan and cetuximab after failure of front-line systemic therapy in subjects with wild-type KRAS alleles.MedDRA version: 14.1Level: LLTClassification code 10052362Term: Metastatic colorectal cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2009-016025-34-DE
- Lead Sponsor
- Daiichi Sankyo Pharma Development
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 150
1. Subjects with surgically unresectable locally advanced or metastatic disease who have received one prior line of chemotherapy, including irinotecan-based chemotherapy. Subjects who received only adjuvant treatment will be eligible if disease progressed less than 6 months after completion of adjuvant therapy. Both relapsed and refractory CRC are allowed. Subjects must have radiologically documented disease progression prior to enrollment.
2. All subjects must express the wild-type form of the gene KRAS.
3. Measurable disease according to Response Evaluation Criteria in Solid Tumors [RECIST], Version 1.1 criteria.
4. Male or female = 18 years of age.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Resolution of any toxic effects of prior therapy (except alopecia) to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0, grade = 1.
7. Adequate bone marrow, liver, and renal functions, defined as:
•Hemoglobin = 9.0 g/dL (transfusion and/or growth factor support allowed).
•Absolute neutrophil count (ANC) = 1.5 × 10^9/L.
•Platelet count = 75 × 10^9/L.
•Serum creatinine = 1.5 × ULN or creatinine clearance = 60 mL/min.
•Alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase = 2.5 × upper limit of normal (ULN) in subjects with no liver metastasis and = 5.0 x ULN in subjects with liver metastasis.
•Total bilirubin = 1.5 x ULN (= 4 x ULN and direct bilirubin = 1.5 x ULN is acceptable for subjects with Gilbert’s syndrome).
8. Male and female subjects of child-bearing potential must agree to use double-barrier contraceptive measures, oral contraception, or avoidance of intercourse during the study and for 90 days after last investigational drug dose received.
9. All female subjects of childbearing potential must each have a negative pregnancy test (serum or urine) result before initiating study treatment.
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 76
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 74
1. Prior therapy with an EGFR inhibitor.
2. History of malignancy other than CRC, unless there is an exception that the malignancy has been cured and no tumor-specific treatment for the malignancy has been administered within the 5 years prior to initiation of study treatment (subjects with a history of basal cell carcinoma or benign tumor of cervix can be enrolled if diagnosis and treatment occurred < 3 years prior to randomization).
3. Anticipation of need for a major surgical procedure or radiation therapy (RT) during the study.
4. Treatment with chemotherapy, radiotherapy, surgery, immunotherapy, biological therapy, or any other investigational anticancer agent within 4 weeks prior to start of study treatment.
5. History of cardiac disease:
•Congestive heart failure defined as Class II to IV per New York Heart Association (NYHA) classification.
•Active coronary artery disease (CAD).
•Previously diagnosed bradycardia or other cardiac arrhythmia defined as Grade 2 or higher according to NCI CTCAE, version 4.0, or uncontrolled hypertension.
•Myocardial infarction that occurred within 6 months prior to start of study treatment (myocardial infarction that occurred > 6 months before the start of study treatment is permitted).
6. Malabsorption syndrome, chronic diarrhea (lasting > 4 weeks), inflammatory bowel disease, or partial bowel obstruction.
7. Known metastatic brain or meningeal tumors, unless the subject is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of first dose of study treatment, and is clinically stable (no concomitant therapy, including supportive therapy with steroids or anticonvulsant medications) with respect to the tumor at the time of first dose of study treatment.
8. Uncontrolled seizure disorder, spinal cord compression, or carcinomatous meningitis.
9. Pericardial or pleural effusion (eg, requiring drainage) or pericardial involvement with the tumor. Subjects with minimal pleural effusion may be eligible upon request by Investigator and approval by Sponsor.
10. Clinically significant active infection that requires antibiotic therapy.
11. Previous administration of ARQ 197(or other known c-MET inhibitor).
12. Substance abuse or medical, psychological or social conditions that may, in the opinion of the Investigator, interfere with the subject’s participation in the clinical trial or evaluation of the clinical trial results.
13. Any condition that is unstable or that could jeopardize the safety of the subject and the subject’s protocol compliance, including known human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
14. Inability to swallow oral medications.
15. Pregnant or nursing females.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To estimate the difference in progression-free survival (PFS) between the study and control arms in subjects with CRC with wild-type KRAS who have received front-line systemic therapy.;Secondary Objective: The secondary objectives are the following:<br>- To estimate the difference between control and study arms in overall survival (OS) and objective response rate (ORR).<br>- To evaluate the safety profile of ARQ 197 in combination with irinotecan and cetuximab.<br>;Primary end point(s): The primary end point is Progression Free Survival (PFS).;Timepoint(s) of evaluation of this end point: NA
- Secondary Outcome Measures
Name Time Method Secondary end point(s): •The secondary end points are overall survival (OS) and objective response rate (ORR).;Timepoint(s) of evaluation of this end point: Overall survival.