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

January 29, 2008
July 20, 2012
April 2007
January 2010   (final data collection date for primary outcome measure)
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 ]
To determine the safety, tolerability and recommended Phase 2 dose (RP2D) of ARQ 197 with continuously twice daily (bid) dosing schedule. [ Time Frame: No time frame ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00612209 on ClinicalTrials.gov Archive Site
  • 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 ]
  • 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: No time frame ] [ Designated as safety issue: No ]
  • To assess the preliminary anti-tumor activity of ARQ 197. [ Time Frame: No time frame ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Phase 1 Study of ARQ 197 in Adult Patients With Advanced Solid Tumors
A Phase 1 Dose Escalation Study of ARQ 197 Given Twice Daily Continuously in Adult Patients With Advanced Solid Tumors

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

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.

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Cancer, Advanced Solid Tumors
Drug: ARQ 197
Treatment with ARQ 197
Experimental: 1
Intervention: Drug: ARQ 197
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
51
February 2010
January 2010   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United Kingdom
 
NCT00612209
ARQ 197-103
No
ArQule
ArQule
Not Provided
Principal Investigator: Johann DeBono, MBChB, FRCP The Royal Marsden Hospital
ArQule
July 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP