Phase 2 Study in Patients With MiT Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
ArQule
ClinicalTrials.gov Identifier:
NCT00557609
First received: November 12, 2007
Last updated: February 6, 2013
Last verified: February 2013
  Purpose

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

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of ARQ 197 in Patients With Microphthalmia Transcription Factor Associated Tumors

Resource links provided by NLM:


Further study details as provided by ArQule:

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

Secondary Outcome Measures:
  • 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

Enrollment: 47
Study Start Date: October 2007
Study Completion Date: February 2011
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: ARQ 197
    360 mg administered twice daily until disease progression or other discontinuation criterion is met
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.

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00557609

Locations
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
  More Information

No publications provided by ArQule

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: ArQule
ClinicalTrials.gov Identifier: NCT00557609     History of Changes
Other Study ID Numbers: ARQ 197-204
Study First Received: November 12, 2007
Last Updated: February 6, 2013
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Canada: Health Canada

Keywords provided by ArQule:
Microphthalmia transcription (MiT) factor associated tumors
Alveolar soft part sarcoma (ASPS)
Clear cell sarcoma (CCS)
Renal cell carcinoma (RCC)

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Sarcoma
Sarcoma, Alveolar Soft Part
Sarcoma, Clear Cell
Adenocarcinoma
Kidney Diseases
Kidney Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Connective and Soft Tissue
Neoplasms, Connective Tissue
Neoplasms, Glandular and Epithelial
Neoplasms, Muscle Tissue
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms

ClinicalTrials.gov processed this record on October 22, 2014