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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
ArQule
ClinicalTrials.gov Identifier:
NCT00612209
First received: January 29, 2008
Last updated: July 20, 2012
Last verified: July 2012
  Purpose

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


Condition Intervention Phase
Cancer, Advanced Solid Tumors
Drug: ARQ 197
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Dose Escalation Study of ARQ 197 Given Twice Daily Continuously in Adult Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by ArQule:

Primary Outcome Measures:
  • Safety, tolerability [ Time Frame: ARQ 197 treatment will be continued until progression of disease, unacceptable toxicity, or another discontinuation criterion is met ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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. [ Time Frame: ARQ 197 treatment will be continued until progression of disease, unacceptable toxicity, or another discontinuation criterion is met ] [ Designated as safety issue: No ]
  • To assess the preliminary anti-tumor activity of ARQ 197. [ Time Frame: ARQ 197 treatment will be continued until progression of disease, unacceptable toxicity, or another discontinuation criterion is met ] [ Designated as safety issue: No ]
  • To determine the pharmacokinetic (PK) profile of ARQ 197 with continuously twice daily oral dosing schedule. [ Time Frame: ARQ 197 treatment will be continued until progression of disease, unacceptable toxicity, or another discontinuation criterion is met ] [ Designated as safety issue: No ]

Enrollment: 51
Study Start Date: April 2007
Study Completion Date: February 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: ARQ 197
Treatment with ARQ 197

Detailed Description:

Patients will take ARQ 197 orally twice daily continuously at dose levels specified for their respective dose cohorts. The ARQ 197 starting dose will be a total daily dose of 200 mg (100 mg bid). ARQ 197 treatment will be continued until progression of disease, unacceptable toxicity, or another discontinuation criterion is met. In the case of toxicity, dose adjustment is permitted. A treatment cycle is designed as four weeks (28 days) and will be repeated without therapy interruption.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

The following inclusion criteria apply to patients with prostate cancer only:

  • Histologically documented adenocarcinoma of the prostate, clinically refractory or resistant to hormone therapy, as documented by progression following castration
  • PSA or radiological evidence for progressive prostate cancer
  • Ongoing gonadal androgen deprivation therapy with LHRH analogues or orchiectomy. Patients who have not had an orchiectomy must be maintained on effective LHRH analogue therapy before and during the trial.
  • Castrate testosterone level [< 50 ng/dL or < 2.00 nmol/L (nmol/L x 28.8 = ng/dL)]

Exclusion Criteria:

  • 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
  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: NCT00612209

Locations
United Kingdom
The Royal Marsden Hospital
Sutton, Surrey, United Kingdom, SM25PT
Sponsors and Collaborators
ArQule
Investigators
Principal Investigator: Johann DeBono, MBChB, FRCP The Royal Marsden Hospital
  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: NCT00612209     History of Changes
Other Study ID Numbers: ARQ 197-103
Study First Received: January 29, 2008
Last Updated: July 20, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by ArQule:
ARQ 197, advanced solid tumors, phase 1, dose escalation, pharmacodynamics, safety

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on September 11, 2014