An Extension Protocol for Subjects Who Were Previously Enrolled in Other Tivantinib (ARQ 197) Protocols

Phase 1

Completed

• Conditions: Advanced Solid Tumors
• Interventions: Drug: Tivantinib; Drug: Anti-Cancer Combination Therapy

• Registration Number: NCT01178411
• Lead Sponsor: ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA)

Brief Summary

This is an extension study that will allow participants to continue to receive study therapy when the original studies into which they were enrolled have reached their designated end-dates. This extension study is designed to further evaluate the safety and tolerability of tivantinib (ARQ 197) monotherapy or in combination with other drug(s) when given to participants who tolerated previous treatment well and may benefit from the continuing treatment.

Detailed Description

This open label extension protocol enrolls participants who were treated in previous phase 1 (NCT01149720, NCT01517399, NCT01699061, NCT00612703, NCT00827177, and NCT00874042) and phase 2 (NCT00777309, NCT00557609, NCT00988741, NCT01395758 , and NCT01055067) tivantinib studies that have reached their designated end-dates. Participants enrolled in this extension protocol will provide further safety and tolerability information about tivantinib monotherapy or in combination with other drug(s) at the same dose(s), and same schedule(s) in which they were originally enrolled.

Study Timeline

• Study First Submitted: 2010-07-21
• Study First Submitted QC: 2010-08-09
• Study First Posted: 2010-08-10
• Study Start: 2010-08-31
• Primary Completion: 2019-01-14
• Study Completion: 2019-01-14
• Results First Submitted: 2021-01-28
• Results First Submitted QC: 2021-01-28
• Status Verified: 2021-02
• Results First Posted: 2021-02-17
• Last Update Submitted: 2021-02-17
• Last Update Posted: 2021-03-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• Signed written informed consent to participate in clinical study of tivantinib

• Male or female participants of the age defined in the original protocol they were enrolled.

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤3 (or ≤2 for tivantinib-naive participants)

• Adequate bone marrow function:

  • Absolute neutrophil count (ANC) ≥1.5 x 10^9/L
  • Hemoglobin ≥8.0 g/dL (or ≥ 9.0 g/dL for tivantinib-naïve participants)

• Enrollment within 14 days of the completion of End of Treatment Visit of the original study

• Participants, who participated in previous ARQ 197 studies that have reached their designated end-dates, who did not meet discontinuation criteria in their original study, and who may, in the opinion of the Investigator and the Sponsor, benefit from treatment

• Women of childbearing potential must have a negative pregnancy test performed within 14 days of the start of study drug. Both men and women enrolled in this study must agree to use adequate birth control measures while on study

Exclusion Criteria

• Known or suspected allergy to ARQ 197

• Substance abuse, medical, psychological or social conditions that may interfere with the participant's participation in the study or evaluation of the study results

• Any condition that is unstable or which could jeopardize the safety of the participant and his/her compliance in the study

• A serious uncontrolled medical disorder/condition that in the opinion of the Investigator would impair the ability of the participant to receive protocol therapy

• Requirement to receive other concurrent chemotherapy (excluding combination therapy defined in original protocol), immunotherapy, radiotherapy, or any other investigational drug while on study. Palliative radiotherapy is allowed provided that:

  • in the opinion of the Investigator, the participant does not have progressive disease
  • the radiation field does not encompass a target lesion
  • no more than 10% of the participant's bone marrow is irradiated

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Tivantinib (Monotherapy or Combination Therapy)	Tivantinib	Tivantinib 360 mg will be administered twice daily, orally, with meals, as a monotherapy or in combination with other drug therapies.
Tivantinib (Monotherapy or Combination Therapy)	Anti-Cancer Combination Therapy	Tivantinib 360 mg will be administered twice daily, orally, with meals, as a monotherapy or in combination with other drug therapies.

Primary Outcome Measures

Name	Time	Method
Extent of Exposure to ARQ 197 in Participants Benefiting From Prior ARQ 197 Therapy	Up to 3,021 days (up to 14-Jan-2019)	The duration of ARQ 197 exposure in this study was calculated as \[(date of last dose of study drug - date of first dose of study drug) + 1\]. Results refer to duration of ARQ 197 treatment in the present study only (i.e., does not include treatment received during participation in "feeder" studies).

Secondary Outcome Measures

Name	Time	Method
Number of Participants Discontinuing Treatment Due to an AE	Up to 3,021 days	An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Number of Participants With ≥1 Treatment-emergent Adverse Event (TEAE)	Up to 3021 days	An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.