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

October 17, 2011 updated by: ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
9

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana Farber Cancer Institute

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

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)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
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
Up to 30 hours after a single dose of ARQ 501

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
To further characterize the safety and tolerability of ARQ 501
To assess anti-tumor activity of ARQ 501

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Geoffrey Shapiro, MD, PhD, Dana-Farber Cancer Institute

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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2007

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2008

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2008

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 30, 2007

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 30, 2007

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 3, 2007

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 19, 2011

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 17, 2011

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ARQ 501-109

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.

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