Phase 2 Study in Patients With MiT Tumors

Sponsor

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

Overall Status

Completed

CT.gov ID

NCT00557609

Collaborator

(none)

Enrollment

Locations

Duration (Months)

5.2

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Study Design

Study Type:

Interventional

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 :

Oct 1, 2007

Actual Primary Completion Date :

Dec 1, 2010

Actual Study Completion Date :

Feb 1, 2011

Outcome Measures

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 []

Eligibility Criteria

Criteria

Ages Eligible for Study:

13 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically or cytologically confirmed unresectable locally advanced or metastatic alveolar soft part sarcoma, clear cell sarcoma, or translocation associated renal cell carcinoma
≥13 years old
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
Females of childbearing potential must have a negative serum pregnancy test

Exclusion Criteria:

Central nervous system metastasis unless it has been stable for ≥ 3 months after treatment and patient has no neural symptoms
Pregnant or lactating
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)
Unable or unwilling to swallow ARQ 197 capsules twice daily
Known human immunodeficiency virus (HIV), Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
Bradycardia at baseline or known history of arrhythmia
Received ARQ 197 previously

Contacts and Locations

Locations

	City	State	Country	Postal Code
1	San Francisco	California	United States	94143
2	Santa Monica	California	United States	90404
3	Miami	Florida	United States	33136
4	Boston	Massachusetts	United States	02115
5	Cincinnati	Ohio	United States	45229
6	Dallas	Texas	United States	75201
7	Houston	Texas	United States	77030
8	Toronto	Ontario	Canada	M5G 2M9
9	London		United Kingdom	SW3 6JJ