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An Exploratory Biomarker Study of ARQ 501 in Patients With Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00524524
Recruitment Status : Completed
First Posted : September 3, 2007
Last Update Posted : October 19, 2011
Sponsor:
Information provided by (Responsible Party):
ArQule

Tracking Information
First Submitted Date  ICMJE August 30, 2007
First Posted Date  ICMJE September 3, 2007
Last Update Posted Date October 19, 2011
Study Start Date  ICMJE August 2007
Actual Primary Completion Date August 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 30, 2007)
To evaluate the pharmacodynamics of a panel of biomarkers following administration of ARQ 501 [ Time Frame: Up to 30 hours after a single dose of ARQ 501 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 30, 2007)
  • To further characterize the safety and tolerability of ARQ 501
  • To assess anti-tumor activity of ARQ 501
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE An Exploratory Biomarker Study of ARQ 501 in Patients With Advanced Solid Tumors
Official Title  ICMJE An Exploratory Biomarker Study of ARQ 501 in Patients With Advanced Solid Tumors
Brief Summary This study is designed to evaluate the response of several biomarkers in patients treated with ARQ 501. The results of the study may help the sponsor understand the effect of the study drug on these biomarkers and their respective role in cancer growth control.
Detailed Description

ARQ 501 is an investigational anticancer agent that consists of a fully synthetic small molecule version of β-lapachone (3,4-dihydro-2,2-dimethyl-2H-naphtho[1,2-b]pyran-5,6-dione) in a stable formulation for intravenous (IV) administration. ARQ 501 selectively induces apoptosis in cancer cells by the direct activation of the cellular checkpoints without damaging deoxyribonucleic acid (DNA) or microtubules. This therapeutic approach is known as Activated Checkpoint Therapy (ACT)sm. ACTsm is a novel strategy for treating and preventing cancers. Cell cycle checkpoints constitute an internal surveillance system that detects cellular, especially genetic, damage and either allows the cells to repair the damage, or induces apoptosis when damage is not repairable. Cancer cells are selectively eliminated upon checkpoint activation due to presence of irreparable DNA damage. It is believed that the rapid and selective induction of apoptosis in cancer cells by ARQ 501 is caused by a correspondingly rapid and sustained increase of the pro-apoptotic protein E2F1.

Preclinical studies have shown that exposure to ARQ 501 results in the activation or inactivation of a panel of 5 biomarkers. Time course changes in human tumor xenograft biomakers in athymic mice after exposure to ARQ 501 can be classified into 3 biomarker groups: those that changed shortly after exposure and returned to normal within 24 hours; those that changed shortly after exposure and remained for 24 hours or longer; and those that changed after 24 hours or later.

The primary objective is to evaluate the response of biomarkers in patients treated with ARQ 501. The exploratory study will help to illuminate the pharmacodynamics of these biomarkers, their roles in the cancer growth control, and their potential predictive or prognostic values for the disease and treatment of ARQ 501 in humans.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Solid Tumors
Intervention  ICMJE Drug: ARQ 501
Weekly IV Infusion; 450 mg/m2
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 17, 2011)
9
Original Estimated Enrollment  ICMJE
 (submitted: August 30, 2007)
15
Actual Study Completion Date  ICMJE August 2008
Actual Primary Completion Date August 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Able to provide signed and dated informed consent prior to study-specific screening procedures.
  2. Patients must have histologically or cytologically confirmed advanced solid tumor(s).
  3. Measurable disease as defined by RECIST (see Section 9.0).
  4. Patients must have Karnofsky performance status (KPS) ≥ 70%.
  5. Male or female patients of child-producing potential must agree to contraception or avoidance of pregnancy measures during the study and for 30 days after the infusion of ARQ 501.
  6. Females of childbearing potential must have a negative serum pregnancy test within seven days prior to the administration of study drug.
  7. ≥ 18 years old.
  8. Hemoglobin ≥ 10 g/dL
  9. Absolute neutrophil count (ANC) ≥ 1.5 x 10 9/L (≥1,500/mm3).
  10. Platelets ≥ 100 x 10 9/L (≥ 100,000/mm3).
  11. Total bilirubin ≤ 1.5 x upper limit of normal (ULN) or ≤ 3.0 x ULN with metastatic liver disease.
  12. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN or ≤ 5.0 x ULN with metastatic liver disease.
  13. Creatinine ≤ 1.5 × ULN

Exclusion Criteria:

  1. Active, uncontrolled systemic infection considered opportunistic, life threatening or clinically significant at the time of treatment
  2. Received anticancer chemotherapy, immunotherapy, radiotherapy, surgery or investigational agents within four weeks of first infusion
  3. Symptomatic or untreated central nervous system (CNS) involvement
  4. Previous exposure to ARQ 501
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00524524
Other Study ID Numbers  ICMJE ARQ 501-109
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party ArQule
Study Sponsor  ICMJE ArQule
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Geoffrey Shapiro, MD, PhD Dana-Farber Cancer Institute
PRS Account ArQule
Verification Date October 2011

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