Phase 2 Study in Patients With MiT Tumors

February 6, 2013 updated by: ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)

A Phase 2 Study of ARQ 197 in Patients With Microphthalmia Transcription Factor Associated Tumors

This is a multi-center, single arm intended to evaluate the anti-tumor effect of ARQ 197 in patients with microphthalmia transcription factor associated (MiT) tumors. MiT tumors include clear cell sarcoma, alveolar soft parts sarcoma, and translocation associated renal cell carcinoma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a multi-center, single arm, two-stage phase 2 study of ARQ 197 in patients with microphthalmia transcription factor associated (MiT) tumors. ARQ 197 is a novel small molecule drug designed to block the activity of c-Met, which is thought to play multiple key roles in human cancer, including cancer cell growth, survival, angiogenesis, invasion and metastasis.

The microphthalmia transcription factor tumors (MiT tumors) are clear cell sarcoma (CCS), alveolar soft part sarcoma (ASPS), and translocation associated renal cell carcinoma (RCC). These soft tissue cancers are characterized by a common transcriptional mechanism that leads to inexorable spread and resistance to all known therapies. They tend to strike adolescents and young adults, and are invariably fatal if not resectable at diagnosis. Several academic laboratories have shown that genetic translocations in these tumors upregulate c-Met, and that such tumors are dependent upon this activity.

The study will enroll adolescent (age 13 or older) and adult patients with a histologically or cytologically confirmed MiT malignant disease. Eligible patients will receive ARQ 197 twice daily. Treatment will be continued until progression of disease, unacceptable toxicity, or another discontinuation criterion is met.

During the study, tumor evaluations will be performed at baseline, then in 8-week intervals.

To evaluate each patient's safety and the drug's toxicity, physical examinations, laboratory evaluations, vitals signs, and adverse event assessments will be performed throughout the study. Blood samples for PK analysis will be collected during first cycle of treatment from up to 10 patients aged 20 or younger. Archival tissue specimens and relevant laboratory results on patients' gene translocation/fusion status will be collected.

Tumor biopsies may also be collected (optional) with patient's consent. If patients agree tumor samples may be collected using core needle biopsy.

In addition, to explore biological responses of tumors to ARQ 197 treatment, FDG-PET scanning will be performed at three time points: within 14 days prior to the treatment, on Day 8 (± 2 days) of Cycle 1 and after two cycles of treatment coinciding with tumor measurement.

Study Type

Interventional

Enrollment (Actual)

47

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
  • United Kingdom
      • London, United Kingdom, SW3 6JJ
  • United States
    • California
      • San Francisco, California, United States, 94143
      • Santa Monica, California, United States, 90404
    • Florida
      • Miami, Florida, United States, 33136
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
    • Ohio
      • Cincinnati, Ohio, United States, 45229
    • Texas
      • Dallas, Texas, United States, 75201
      • Houston, Texas, United States, 77030

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

13 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Histologically or cytologically confirmed unresectable locally advanced or metastatic alveolar soft part sarcoma, clear cell sarcoma, or translocation associated renal cell carcinoma
  2. ≥13 years old
  3. Male or female patients of child-producing potential must agree to use double barrier contraception, oral contraceptives or avoidance of pregnancy measures during the study and for 30 days after the last ARQ 197 dose
  4. Females of childbearing potential must have a negative serum pregnancy test

Exclusion Criteria:

  1. Central nervous system metastasis unless it has been stable for ≥ 3 months after treatment and patient has no neural symptoms
  2. Pregnant or lactating
  3. Significant gastrointestinal disorder(s), in the opinion of a Investigator, could interfere with the absorption of ARQ 197 (e.g., Crohn's disease, ulcerative colitis, extensive gastric or small bowel resection)
  4. Unable or unwilling to swallow ARQ 197 capsules twice daily
  5. Known human immunodeficiency virus (HIV), Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
  6. Bradycardia at baseline or known history of arrhythmia
  7. Received ARQ 197 previously

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Determine the overall response rate (ORR) in patients treated with ARQ 197

Secondary Outcome Measures

Outcome Measure
Evaluate progression-free survival (PFS) time in patients treated with ARQ 197
Evaluate 6-month and 1-year overall survival (OS) rates in patients treated with ARQ 197
Further characterize the safety of ARQ 197 in adolescent and young adult patients with MiT tumors

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2007

Primary Completion (Actual)

December 1, 2010

Study Completion (Actual)

February 1, 2011

Study Registration Dates

First Submitted

November 12, 2007

First Submitted That Met QC Criteria

November 12, 2007

First Posted (Estimate)

November 14, 2007

Study Record Updates

Last Update Posted (Estimate)

February 8, 2013

Last Update Submitted That Met QC Criteria

February 6, 2013

Last Verified

February 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ARQ 197-204

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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