A Phase 1 Study of ARQ 197 in Adult Patients With Advanced Solid Tumors

NCT00612209 | Completed Phase 1

• 1 other identifier: ARQ 197-103
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open label, single arm, dose escalation study of ARQ 197 in patients with advanced solid tumors.

Conditions

Cancer, Advanced Solid Tumors

Keywords

ARQ 197, advanced solid tumors, phase 1, dose escalation, pharmacodynamics, safety

Outcome Measures

Primary Outcomes (1)

• Safety, tolerability

  ARQ 197 treatment will be continued until progression of disease, unacceptable toxicity, or another discontinuation criterion is met

Secondary Outcomes (3)

• To evaluate pharmacodynamics of phosphorylated c-Met, total c-Met, apoptosis marker (TUNEL) and phosphorylated FAK in tumor tissue correlated with administration of ARQ 197.

  ARQ 197 treatment will be continued until progression of disease, unacceptable toxicity, or another discontinuation criterion is met

• To assess the preliminary anti-tumor activity of ARQ 197.

  ARQ 197 treatment will be continued until progression of disease, unacceptable toxicity, or another discontinuation criterion is met

• To determine the pharmacokinetic (PK) profile of ARQ 197 with continuously twice daily oral dosing schedule.

  ARQ 197 treatment will be continued until progression of disease, unacceptable toxicity, or another discontinuation criterion is met

Study Arms (1)

1

EXPERIMENTAL

Drug: ARQ 197

Interventions

ARQ 197 DRUG

Treatment with ARQ 197

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent must be obtained and documented according to ICH GCP, the local regulatory requirements, and permission to use private health information in accordance with HIPPA prior to study-specific screening procedures
• A histologically or cytologically confirmed advanced solid tumor, including 10 patients with advanced prostate cancers in the expansion cohort.
• ≥ 18 years of age.
• Patients must have accessible tumor that is safely amenable to tumor biopsies.
• Measurable disease as defined by Response Evaluation Criteria in Solid Tumors
• Tumor imageable by DCE-MRI preferably \> 3cm in abdomen, pelvis, head/neck or peripheral limb (only for 12 patients undergoing MRI studies including DCE-MRI and DW-MRI in the expanded cohort)
• Karnofsky performance status (KPS) ≥ 70% or Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
• Male or female patients of child-producing potential must agree to use contraception 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
• Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 × upper limit of normal (ULN) or ≤ 5.0 × ULN with metastatic liver disease
• Hemoglobin ≥ 10 g/dl
• Total bilirubin ≤ 1.5 × ULN
• Creatinine ≤ 1.5 x ULN
• Absolute neutrophil count ≥ 1.5 x 10\^9/L
• Platelets ≥ 100 x 10\^9/L

You may not qualify if:

• Anti-cancer chemotherapy, radiotherapy, immunotherapy, or investigational agents within four weeks prior to first dose of ARQ 197
• Surgery within 4 weeks prior to first dose
• Known untreated brain metastases
• Pregnant or breastfeeding
• Significant gastrointestinal disorder(s), in the opinion of the Principal Investigator, (e.g., Crohn's disease, ulcerative colitis, extensive gastric resection)
• Unable or unwilling to swallow ARQ 197 capsules twice daily
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, clinically significant non-healing or healing wounds, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, significant pulmonary disease (shortness of breath at rest or mild exertion), uncontrolled infection or psychiatric illness/social situations that would limit compliance with study requirements
• For patients undergoing magnetic resonance imaging (MRI) studies (including DCE-MRI and DW-MRI) in the expanded cohort:
• Contraindications to MRI, e.g. contraindicated metal implants
• Patients with Creatinine \> x1 ULN
• Patients without antecubital fossa venous access

Sponsors & Collaborators

• ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA): lead

Study Sites (1)

The Royal Marsden Hospital

Sutton, Surrey, SM25PT, United Kingdom

Location

Related Publications (1)

• Yap TA, Olmos D, Brunetto AT, Tunariu N, Barriuso J, Riisnaes R, Pope L, Clark J, Futreal A, Germuska M, Collins D, deSouza NM, Leach MO, Savage RE, Waghorne C, Chai F, Garmey E, Schwartz B, Kaye SB, de Bono JS. Phase I trial of a selective c-MET inhibitor ARQ 197 incorporating proof of mechanism pharmacodynamic studies. J Clin Oncol. 2011 Apr 1;29(10):1271-9. doi: 10.1200/JCO.2010.31.0367. Epub 2011 Mar 7.

  PMID: 21383285 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

ARQ 197

Study Officials

• Johann DeBono, MBChB, FRCP

  The Royal Marsden Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2008
• First Posted: February 11, 2008
• Study Start: April 1, 2007
• Primary Completion: January 1, 2010
• Study Completion: February 1, 2010
• Last Updated: July 23, 2012

Record last verified: 2012-07

Locations

GB (1)