NCT00557609

Phase 2 Study in Patients With MiT Tumors

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

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 47 (actual)
• Sponsor: ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA) · Industry
• Sex: All
• Age: 13 Years
• Healthy volunteers: Not accepted

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.

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.

Conditions

• Renal Cell Carcinoma (RCC)
• Alveolar Soft Part Sarcoma (ASPS)
• Clear Cell Sarcoma (CCS)

Interventions

Type	Name	Description
DRUG	ARQ 197	360 mg administered twice daily until disease progression or other discontinuation criterion is met

Timeline

• Start date: 2007-10-01
• Primary completion: 2010-12-01
• Completion: 2011-02-01
• First posted: 2007-11-14
• Last updated: 2013-02-08

Locations

9 sites across 3 countries: United States, Canada, United Kingdom