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

NCT01075048 | Completed Phase 1 Results DMC

• 1 other identifier: ARQ197-A-U252
• Study Type: interventional
• Target: 131
• Locations: 5 countries
• Sites: 40

Brief Summary

ARQ 197 or placebo in combination with irinotecan and cetuximab in participants with metastatic colorectal cancer (CRC), in participants 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. After the recommended dose is determined for Phase 2, participants receive study drug or placebo with irinotecan and cetuximab.

Conditions

Metastatic Colorectal Cancer

Keywords

Colorectal cancer; wild-type KRAS; irinotecan; cetuximab; second-line therapy

Outcome Measures

Primary Outcomes (2)

• Progression-Free Survival (PFS) Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer With Wild-Type K-ras Oncogene (KRAS) Who Have Received Front-Line Systemic Therapy

  Progression-free survival is defined as the time from randomization to the date of disease progression (PD) or death due to any cause (as of data cutoff 12 Oct 2012).

  Baseline up to 80 weeks postdose

• Progression-Free Survival (PFS) Using Computed Best Response Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy

  Progression-free survival is defined as the time from randomization to the date of disease progression (PD) or death due to any cause (as of data cutoff 12 Oct 2012).

  Baseline up to 80 weeks postdose

Secondary Outcomes (5)

• Best Overall Tumor Response and Objective Response Rate Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Subjects With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy

  Baseline up to 2 years 10 months postdose

• Overall Survival (OS) Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer With Wild-Type K-ras Oncogene (KRAS) Who Have Received Front-Line Systemic Therapy

  Baseline up to 5 years 1 month postdose

• Duration of Response and Stable Disease Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer With Wild-Type KRAS Who Have Received Front-Line Systemic Therapy

  Baseline up to 80 weeks postdose

• Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Subjects With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy

  Baseline up to 30 days after last dose, up to 5 years 1 month

• Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy

  Baseline up to 30 days after last dose, up to 5 years 1 month

Study Arms (3)

Phase 2: Tivantinib, cetuximab, irinotecan

EXPERIMENTAL

Tivantinib in combination with irinotecan and cetuximab.

Drug: Tivantinib; Drug: Cetuximab; Drug: Irinotecan

Phase 2: Placebo, cetuximab, irinotecan

PLACEBO COMPARATOR

Placebo in combination with irinotecan and cetuximab

Drug: Placebo; Drug: Cetuximab; Drug: Irinotecan

Phase 1: Tivantinib, cetuximab, irinotecan

EXPERIMENTAL

Tivantinib in combination with irinotecan and cetuximab.

Drug: Tivantinib; Drug: Cetuximab; Drug: Irinotecan

Interventions

Tivantinib DRUG

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.

Also known as: ARQ 197

Phase 1: Tivantinib, cetuximab, irinotecan; Phase 2: Tivantinib, cetuximab, irinotecan

Placebo DRUG

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

Phase 2: Placebo, cetuximab, irinotecan

Cetuximab DRUG

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

Phase 1: Tivantinib, cetuximab, irinotecan; Phase 2: Placebo, cetuximab, irinotecan; Phase 2: Tivantinib, cetuximab, irinotecan

Irinotecan DRUG

60 minutes after cetuximab, Irinotecan 180 mg/m\^2 intravenous infusion over 30 - 90 minutes. Administered on Day 1 and Day 15 of each 28 day cycle. Administered until disease progression, unacceptable toxicity or other discontinuation criteria is met.

Phase 1: Tivantinib, cetuximab, irinotecan; Phase 2: Placebo, cetuximab, irinotecan; Phase 2: Tivantinib, cetuximab, irinotecan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants 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.
• All participants must express the wild-type form of the gene KRAS.
• Measurable disease according to RECIST (Response Evaluation Criteria In Solid Tumors) criteria, Version 1.1.
• Male or female \>= to 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Resolution of any toxic effects of prior therapy (except alopecia) to NCI CTCAE, Version 4.0, grade \<= to 1.
• 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 participants 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).
• Male and female participants 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.
• All female participants of childbearing potential must each have a negative pregnancy test (serum or urine) result before initiating study treatment.

You may not qualify if:

• Prior therapy with an Epidermal Growth Factor Receptor (EGFR) inhibitor.
• 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 (participants 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).
• Anticipation of need for a major surgical procedure or radiation therapy (RT) during the study.
• Treatment with chemotherapy, radiotherapy, surgery, immunotherapy, biological therapy, or any other investigational anticancer agent within 4 weeks prior to start of study treatment.
• 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).
• Malabsorption syndrome, chronic diarrhea (lasting greater than 4 weeks), inflammatory bowel disease, or partial bowel obstruction.
• Known metastatic brain or meningeal tumors, unless the participant 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.
• Uncontrolled seizure disorder, spinal cord compression, or carcinomatous meningitis.
• Pericardial or pleural effusion (eg, requiring drainage) or pericardial involvement with the tumor. Participants with minimal pleural effusion may be eligible upon request by Investigator and approval by Sponsor.
• Clinically significant active infection that requires antibiotic therapy.
• Previous administration of ARQ 197.

Sponsors & Collaborators

• Daiichi Sankyo: lead

Study Sites (40)

Unknown Facility

Beverly Hills, California, 90211-1850, United States

Location

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Encinitas, California, 92024, United States

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Fountain Valley, California, 92708, United States

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Riverside, California, 92501, United States

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Fort Collins, Colorado, 80528, United States

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Norwich, Connecticut, 06360, United States

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Boynton Beach, Florida, 33435, United States

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Fort Myers, Florida, 33916, United States

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Orlando, Florida, 32836, United States

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Centralia, Illinois, 62801, United States

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Metairie, Louisiana, 70006, United States

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Baltimore, Maryland, 21237, United States

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Hagerstown, Maryland, 21740, United States

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Omaha, Nebraska, 68114, United States

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Buffalo, New York, 14263, United States

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Lake Success, New York, 11042, United States

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Canton, Ohio, 44718, United States

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Cincinnati, Ohio, 45242, United States

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Oklahoma City, Oklahoma, 73104, United States

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Charleston, South Carolina, 29403, United States

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Columbia, South Carolina, 29210, United States

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Nashville, Tennessee, 372203, United States

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Houston, Texas, 77030, United States

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Seattle, Washington, 98104, United States

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Bayonne, 64100, France

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Lille, 59020, France

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Marseille, 13285, France

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Halle, Germany

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Leer, 26789, Germany

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Mannheim, 68167, Germany

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München, 81675, Germany

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Milan, 20089, Italy

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Reggio Emilia, 42100, Italy

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Treviglio, 24047, Italy

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Chelyabinsk, 454087, Russia

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Kursk, 305035, Russia

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Moscow, 125367, Russia

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Pyatigorsk, 357502, Russia

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Saint Petersburg, 194044, Russia

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Samara, 443031, Russia

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MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

ARQ 197; Cetuximab; Irinotecan

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Camptothecin; Alkaloids; Heterocyclic Compounds

Results Point of Contact

• Title: Contact for Clinical Trial Information
• Organization: Daiichi Sankyo

CTRinfo@dsi.com

908-992-6400

Study Officials

• Clinical Study Leader

  Daiichi Sankyo

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1 is single group open label with one arm. Phase 2 is parallel, double-blind design with two arms.

Study Record Dates

• First Submitted: February 17, 2010
• First Posted: February 24, 2010
• Study Start: January 26, 2010
• Primary Completion: October 12, 2012
• Study Completion: February 20, 2015
• Last Updated: April 8, 2021
• Results First Posted: August 14, 2020

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (4); RU (6); US (24); FR (3); IT (3)