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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
ArQule
ClinicalTrials.gov Identifier:
NCT00524524
First received: August 30, 2007
Last updated: October 17, 2011
Last verified: October 2011
  Purpose

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.


Condition Intervention Phase
Advanced Solid Tumors
Drug: ARQ 501
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Exploratory Biomarker Study of ARQ 501 in Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by ArQule:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To further characterize the safety and tolerability of ARQ 501 [ Designated as safety issue: No ]
  • To assess anti-tumor activity of ARQ 501 [ Designated as safety issue: No ]

Enrollment: 9
Study Start Date: August 2007
Study Completion Date: August 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: ARQ 501
    Weekly IV Infusion; 450 mg/m2
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.

  Eligibility

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

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
  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: NCT00524524

Locations
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
ArQule
Investigators
Principal Investigator: Geoffrey Shapiro, MD, PhD Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: ArQule
ClinicalTrials.gov Identifier: NCT00524524     History of Changes
Other Study ID Numbers: ARQ 501-109
Study First Received: August 30, 2007
Last Updated: October 17, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by ArQule:
solid tumors
biopsy

Additional relevant MeSH terms:
Neoplasms
Beta-lapachone
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Antiviral Agents

ClinicalTrials.gov processed this record on September 14, 2014