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Phase 2 Study in Patients With MiT Tumors

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ClinicalTrials.gov Identifier: NCT00557609
Recruitment Status : Completed
First Posted : November 14, 2007
Last Update Posted : February 8, 2013
Information provided by (Responsible Party):
ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Renal Cell Carcinoma (RCC) Alveolar Soft Part Sarcoma (ASPS) Clear Cell Sarcoma (CCS) Drug: ARQ 197 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 47 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of ARQ 197 in Patients With Microphthalmia Transcription Factor Associated Tumors
Study Start Date : October 2007
Actual Primary Completion Date : December 2010
Actual Study Completion Date : February 2011

Intervention Details:
  • Drug: ARQ 197
    360 mg administered twice daily until disease progression or other discontinuation criterion is met

Primary Outcome Measures :
  1. Determine the overall response rate (ORR) in patients treated with ARQ 197

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

Information from the National Library of Medicine

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Ages Eligible for Study:   13 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00557609

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United States, California
San Francisco, California, United States, 94143
Santa Monica, California, United States, 90404
United States, Florida
Miami, Florida, United States, 33136
United States, Massachusetts
Boston, Massachusetts, United States, 02115
United States, Ohio
Cincinnati, Ohio, United States, 45229
United States, Texas
Dallas, Texas, United States, 75201
Houston, Texas, United States, 77030
Canada, Ontario
Toronto, Ontario, Canada, M5G 2M9
United Kingdom
London, United Kingdom, SW3 6JJ
Sponsors and Collaborators
ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)
ClinicalTrials.gov Identifier: NCT00557609    
Other Study ID Numbers: ARQ 197-204
First Posted: November 14, 2007    Key Record Dates
Last Update Posted: February 8, 2013
Last Verified: February 2013
Keywords provided by ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.):
Microphthalmia transcription (MiT) factor associated tumors
Alveolar soft part sarcoma (ASPS)
Clear cell sarcoma (CCS)
Renal cell carcinoma (RCC)
Additional relevant MeSH terms:
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Carcinoma, Renal Cell
Sarcoma, Alveolar Soft Part
Sarcoma, Clear Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Connective and Soft Tissue
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Neoplasms, Muscle Tissue
Neoplasms, Connective Tissue