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

Phase 1
18 Years
Not Enrolling
Advanced Solid Tumors

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Trial Information

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

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.

Inclusion Criteria:

1. Able to provide signed and dated informed consent prior to study-specific screening

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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To evaluate the pharmacodynamics of a panel of biomarkers following administration of ARQ 501

Outcome Time Frame:

Up to 30 hours after a single dose of ARQ 501

Safety Issue:


Principal Investigator

Geoffrey Shapiro, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Dana-Farber Cancer Institute


United States: Food and Drug Administration

Study ID:

ARQ 501-109



Start Date:

August 2007

Completion Date:

August 2008

Related Keywords:

  • Advanced Solid Tumors
  • solid tumors
  • biopsy
  • Neoplasms



Dana Farber Cancer InstituteBoston, Massachusetts  02115