ARQ 197 in Combination With Chemotherapy in Patients With Metastatic Colorectal Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo Inc.
ClinicalTrials.gov Identifier:
NCT01075048
First received: February 17, 2010
Last updated: April 16, 2014
Last verified: April 2014
  Purpose

ARQ 197 or placebo in combination with irinotecan and cetuximab in patients with metastatic colorectal cancer (CRC), in subjects with wild-type KRAS alleles who have failed front-line systemic therapy, to evaluate the safety, tolerability, and efficacy of ARQ 197, define the recommended dose for Phase 2.


Condition Intervention Phase
Metastatic Colorectal Cancer
Drug: Tivantinib (ARQ 197) + cetuximab + irinotecan
Drug: Placebo + cetuximab + irinotecan
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Placebo-Controlled, Phase 1/2 Study Of ARQ 197 in Combination With Irinotecan and Cetuximab in Subjects With Metastatic Colorectal Cancer With Wild-type KRAS Who Have Received Front-Line Systemic Therapy

Resource links provided by NLM:


Further study details as provided by Daiichi Sankyo Inc.:

Primary Outcome Measures:
  • Phase 1: To evaluate the safety and tolerability of ARQ 197 when administered with irinotecan and cetuximab in subjects who have received front-line systemic therapy [ Time Frame: Phase 1: approximately 24 weeks ] [ Designated as safety issue: No ]
  • Phase 2: 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 therapy. [ Time Frame: Phase 2: approximately 20 months ] [ Designated as safety issue: No ]
  • Phase 1: To define the recommended dose of ARQ 197, in combination with irinotecan and cetuximab for the Phase 2 study. [ Time Frame: Approximately 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Evaluate overall survival (OS), objective response rate (ORR), and safety profile of ARQ 197 in combination with cetuximab and irinotecan. [ Time Frame: Phase 2: approximately 20 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 150
Study Start Date: January 2010
Estimated Study Completion Date: September 2014
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase 2: ARQ 197, cetuximab, irinotecan
The Phase 2 portion is designed as a randomized, double-blind, placebo-controlled study to assess the efficacy and safety of ARQ 197 in combination with irinotecan and cetuximab.
Drug: Tivantinib (ARQ 197) + cetuximab + irinotecan

ARQ 197 is supplied as a 120-mg capsule, administered twice daily at the dose determined in the Phase 1 portion of the study. Administered until disease progression, unacceptable toxicity or other discontinuation criteria is met.

Cetuximab 500 mg/ m^2 intravenous infusion over 120 minutes at the first cycle, then over 60-minutes at subsequent cycles. Followed 60 minutes later with Irinotecan 180 mg/m^2 intravenous infusion over 30 - 90 minutes. Cetuximab and Irinotecan are administered on Day 1 and Day 15 of each 28 day cycle. Administered until disease progression, unacceptable toxicity or other discontinuation criteria is met.

Other Name: Tivantinib
Placebo Comparator: Phase 2: placebo, cetuximab, irinotecan
The Phase 2 portion is designed as a randomized, double-blind, placebo-controlled study to assess the efficacy and safety of placebo in combination with irinotecan and cetuximab.
Drug: Placebo + cetuximab + irinotecan

Placebo to match ARQ 197, administered twice daily. Administered until disease progression, unacceptable toxicity or other discontinuation criteria is met.

Cetuximab 500 mg/ m^2 intravenous infusion over 120 minutes, then over 60 minutes at subsequent cycles. Followed 60 minutes later with Irinotecan 180 mg/m^2 intravenous infusion over 30 - 90 minutes. Cetuximab and Irinotecan are administered on Day 1 and Day 15 of each 28 day cycle. Administered until disease progression, unacceptable toxicity or other discontinuation criteria is met.


Detailed Description:

Phase 1/2 Multicenter study:

  • Phase 1 portion is open-label to evaluate the safety of ARQ 197 administered in combination with irinotecan and cetuximab.
  • Phase 2 portion is designed as a randomized, double-blind placebo-controlled study to assess the efficacy and safety of ARQ 197 or matching placebo administered in combination with irinotecan and cetuximab.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subjects with surgically unresectable locally advanced or metastatic disease who have received one prior line of chemotherapy. (The Phase 1 portion of the study will be open for enrollment for subjects who received 1 or more prior therapies). Both relapsed and refractory CRC are allowed.
  2. All subjects must express the wild-type form of the gene KRAS.
  3. Measurable disease according to RECIST (Response Evaluation Criteria In Solid Tumors) criteria, Version 1.1.
  4. Male or female >= to 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 NCI CTCAE, Version 4.0, grade <= to 1.
  7. Adequate bone marrow, liver, and renal functions, defined as:

    • Hemoglobin >= to 9.0 g/dL (transfusion and/or growth factor support allowed).
    • Absolute neutrophil count (ANC) >= to 1.5 x 10^9/L.
    • Platelet count >= to 75 x 10^9/L.
    • Serum creatinine <= to 1.5 x upper limit of normal (ULN) or creatinine clearance >= to 60 mL/min.
    • Alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase <= to 2.5 x ULN in subjects with no liver metastasis and <= to 5.0 x ULN in subjects with liver metastasis.
    • Total bilirubin <= to 1.5 x ULN (<= to 4 x ULN and direct bilirubin <= to 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.
  10. Subjects must be fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible side effects) and must sign and date an Independent Ethics Committee (IEC) or Institutional Review Board (IRB)-approved informed consent form (ICF) (including HIPAA authorization, if applicable) before performance of any study specific procedures or tests.

Exclusion Criteria:

  1. Prior therapy with an Epidermal Growth Factor Receptor (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 less than 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 greater than 6 months before the start of study treatment is permitted).
  6. Malabsorption syndrome, chronic diarrhea (lasting greater than 4 weeks), inflammatory bowel disease, or partial bowel obstruction.
  7. Known metastatic brain or meningeal tumors, unless the subject is greater than 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.
  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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01075048

  Show 40 Study Locations
Sponsors and Collaborators
Daiichi Sankyo Inc.
Investigators
Study Chair: Cathy Eng, MD M.D. Anderson Cancer Center
  More Information

No publications provided

Responsible Party: Daiichi Sankyo Inc.
ClinicalTrials.gov Identifier: NCT01075048     History of Changes
Other Study ID Numbers: ARQ197-A-U252
Study First Received: February 17, 2010
Last Updated: April 16, 2014
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Daiichi Sankyo Inc.:
Colorectal cancer
wild-type KRAS
irinotecan
cetuximab
second-line therapy

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Cetuximab
Irinotecan
Camptothecin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 16, 2014