- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00612209
A Phase 1 Study of ARQ 197 in Adult Patients With Advanced Solid Tumors (ARQ 197)
July 20, 2012 updated by: ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)
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.
Study Overview
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.
Study Type
Interventional
Enrollment (Actual)
51
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Surrey
-
Sutton, Surrey, United Kingdom, SM25PT
- The Royal Marsden Hospital
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 1
|
Treatment with ARQ 197
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Safety, tolerability
Time Frame: ARQ 197 treatment will be continued until progression of disease, unacceptable toxicity, or another discontinuation criterion is met
|
ARQ 197 treatment will be continued until progression of disease, unacceptable toxicity, or another discontinuation criterion is met
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
|
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.
Time Frame: ARQ 197 treatment will be continued until progression of disease, unacceptable toxicity, or another discontinuation criterion is met
|
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.
Time Frame: ARQ 197 treatment will be continued until progression of disease, unacceptable toxicity, or another discontinuation criterion is met
|
ARQ 197 treatment will be continued until progression of disease, unacceptable toxicity, or another discontinuation criterion is met
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Johann DeBono, MBChB, FRCP, The Royal Marsden Hospital
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
April 1, 2007
Primary Completion (Actual)
January 1, 2010
Study Completion (Actual)
February 1, 2010
Study Registration Dates
First Submitted
January 29, 2008
First Submitted That Met QC Criteria
January 29, 2008
First Posted (Estimate)
February 11, 2008
Study Record Updates
Last Update Posted (Estimate)
July 23, 2012
Last Update Submitted That Met QC Criteria
July 20, 2012
Last Verified
July 1, 2012
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- ARQ 197-103
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Cancer, Advanced Solid Tumors
-
AmgenCompletedCancer | Advanced Solid Tumors | Solid Tumors | Tumors | Advanced MalignancyUnited States, Australia
-
NantCell, Inc.CompletedQUILT-2.016: Study of AMG 479 With Biologics or Chemotherapy for Subjects With Advanced Solid TumorsCancer | Advanced Solid Tumors | Solid Tumors | Tumors | Advanced Malignancy
-
AstraZenecaTerminatedCancer | Advanced Solid Tumors | Advanced Solid MalignanciesUnited States
-
PfizerTerminatedAdvanced Solid Tumors | Advanced CancerUnited States
-
University of California, San FranciscoMerck Sharp & Dohme LLCCompletedCancer | Advanced Solid Tumors | TumorsUnited States
-
AstraZenecaTerminatedSolid Tumors | Advanced Solid Malignancies | Cancer,United States
-
AstraZenecaCompletedCancer | Solid Tumors | Advanced Solid MalignanciesJapan
-
AstraZenecaTerminatedCancer | Solid Tumors | Advanced Solid MalignanciesJapan
-
Amsterdam UMC, location VUmcCompletedCancer | Advanced Solid TumorsNetherlands
-
Onconova Therapeutics, Inc.CompletedNeoplasms | Cancer | Advanced Cancer | Solid TumorsUnited States
Clinical Trials on ARQ 197
-
National Cancer Institute (NCI)TerminatedEpithelioid Mesothelioma | Sarcomatoid Mesothelioma | Stage IV Pleural Mesothelioma | Recurrent Malignant Mesothelioma | Stage II Pleural Mesothelioma | Stage III Pleural MesotheliomaUnited States
-
National Cancer Institute (NCI)CompletedChildhood Solid NeoplasmUnited States, Canada
-
National Cancer Institute (NCI)CompletedStage IV Breast Cancer | Recurrent Breast Carcinoma | Estrogen Receptor Negative | HER2/Neu Negative | Progesterone Receptor Negative | Triple-Negative Breast CarcinomaUnited States
-
Daiichi Sankyo, Inc.ICON Clinical Research; ArQule, Inc. (a wholly owned subsidiary of Merck Sharp...Completed
-
ArQule, Inc. (a wholly owned subsidiary of Merck...CompletedRenal Cell Carcinoma (RCC) | Alveolar Soft Part Sarcoma (ASPS) | Clear Cell Sarcoma (CCS)United States, Canada, United Kingdom
-
ArQule, Inc. (a wholly owned subsidiary of Merck...Completed
-
National Cancer Institute (NCI)CompletedProstate Adenocarcinoma | Recurrent Prostate Carcinoma | Stage IV Prostate Cancer | Hormone-Resistant Prostate CancerUnited States
-
Kyowa Kirin Co., Ltd.Completed
-
ArQule, Inc. (a wholly owned subsidiary of Merck...CompletedHepatocellular Carcinoma | CirrhosisSpain, United States, Italy
-
ArQule, Inc. (a wholly owned subsidiary of Merck...Completed