Clinical Trial of ARQ 761 in Advanced Solid Tumors

NCT01502800 | Completed Phase 1 DMC

• 2 other identifiers: STU 042011-005NCI-2011-03317
• Study Type: interventional
• Target: 91
• Locations: 1 country
• Sites: 1

Brief Summary

Primary Objective: To determine the safety, tolerability and recommended Phase 2 dose (RP2D) of ARQ 761 administered intravenously. Secondary Objectives: To determine the pharmacokinetic profile of ARQ 761 To assess the preliminary anti-tumor activity of aRQ 761

Conditions

Solid Tumors

Keywords

Metastatic; Unresectable; Recurrent advanced

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD)

  To determine the recommended Phase 2 dose (RP2D) of ARQ 761 administered intravenously.

  Patients will receive an average of 4 cycles of ARQ 761 (corresponding with a treatment cycle of 16 weeks).

Secondary Outcomes (1)

• Pharmacokinetic profile of ARQ761

  Samples will be drawn from each subject during first and fourth infusion of study drug

Study Arms (4)

Part 1 (ARQ 761)

EXPERIMENTAL

ARQ 761 (beta lapachone) will be given once a week. The same dose of ARQ761 each week for 4 weeks (1 cycle = 28 days). The total infusion time will be one (1) hour. Beginning dose level will be 195 mg/m2 and will increase until the maximum tolerated dose is defined. Seven dose levels that may be administered: 1-195 mg/m2 2-390 mg/m2 3-450 mg/m2 4-550 mg/m2 5-660 mg/m2 6-800 mg/m2 7-1000 mg/m2

Drug: ARQ 761

Part 2 Arm A

EXPERIMENTAL

The same dose of ARQ761 will be given each week for 8 weeks. The total infusion time will be 2 or 3 hours. Beginning dose level will be 390 mg/m2.

Drug: ARQ 761 Weekly Administration

Part 2 Arm B

EXPERIMENTAL

ARQ 761 (beta lapachone) will be given bi-weekly for 8 weeks. The total infusion time may be either 2 or 3 hours. The beginning dose level will be 390 mg/m2.

Drug: Bi-Weekly Administration of ARQ 761

Part 2 Arm C

EXPERIMENTAL

ARQ 761 (beta lapachone) will be given 2 consecutive weeks followed by one week of rest for 6 weeks. The total infusion time will be 2 or 3 hours. The beginning dose level will be 390 mg/m2.

Drug: Two Consecutive Weeks Administration of ARQ 761 with one week of rest

Interventions

ARQ 761 DRUG

ARQ 761 will be administered intravenously at a starting dose of 195 mg/m2 IV once weekly. Depending on toxicities observed, up to seven treatment cohorts will be enrolled with dose escalation occurring by doubling (first escalation) and 40% increments thereafter. If dosing is tolerated at all levels and pharmacokinetic data suggest continued escalation is warranted, additional dose levels will

Also known as: Beta-Lapachone

Part 1 (ARQ 761)

ARQ 761 Weekly Administration DRUG

If you decide to participate in this study ARQ 761 (beta lapachone) will be given to you through your vein once a week via a Portacath or Hickman line (a device that will make it easier to access your central vein that will be placed under your skin in your upper chest) You will receive the same dose of ARQ761 each week for 8 weeks. The total infusion time will be determined by your physician, it may be either 2 or 3 hours. The beginning dose level will be 390 mg/m2.

Part 2 Arm A

Bi-Weekly Administration of ARQ 761 DRUG

If you decide to participate in this study ARQ 761 (beta lapachone) will be given to you through your vein bi-weekly via a Portacath or Hickman line (a device that will make it easier to access your central vein that will be placed under your skin in your upper chest) You will receive the same dose of ARQ761 bi-weekly for 8 weeks. The total infusion time will be determined by your physician, it may be either 2 or 3 hours. The beginning dose level will be 390 mg/m2.

Part 2 Arm B

Two Consecutive Weeks Administration of ARQ 761 with one week of rest DRUG

If you decide to participate in this study ARQ 761 (beta lapachone) will be given to you through your vein once a week via a Portacath or Hickman line (a device that will make it easier to access your central vein that will be placed under your skin in your upper chest) You will receive the same dose of ARQ761 for 2 consecutive weeks followed by one week of rest for 6 weeks. The total infusion time will be determined by your physician, it may be either 2 or 3 hours. The beginning dose level will be 390 mg/m2.

Part 2 Arm C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must have a confirmed solid tumor that is metastatic, unresectable or recurrent and for which standard curative or palliative measures do not exist or are no longer effective.
• Prior and concurrent therapy:
• Chemotherapy: At least four weeks since prior cytotoxic chemotherapy or 6 weeks since nitrosoureas or mitomycin.
• Molecular targeted agents including monoclonal antibodies and tyrosine kinase inhibitors: At least two weeks since last therapy.
• Endocrine therapy: Subject may be remain on LHRH antagonist therapy for prostate cancer if tumor progression has been confirmed.
• Radiotherapy: At least 3 weeks since most recent radiotherapy. Other investigational therapy: At least four weeks since any other investigational therapy.
• Concurrent therapy: No other concurrent anticancer or investigational therapy permitted except as noted above.
• Measurable disease is not required, but will be evaluated in each subject when possible.
• Age ≥18 years
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
• Life expectancy ≥ three months.
• Central venous access, such as a Portacath or Hickman Line.
• Pretreatment clinical laboratory parameters within 14 days
• Availability of 10 unstained slides or paraffin-embedded tissue block from archived tumor specimen.
• Subjects must be recovered from any toxicity related to prior anti-neoplastic therapy (to grade \<1). Patients with CTCAE grade 2 or less sensory neuropathy or any grade alopecia are eligible.

You may not qualify if:

• Subjects who have had cytotoxic chemotherapy or treatment with monoclonal antibodies within 4 weeks, radiotherapy within 3 weeks, or other molecular targeted therapies.
• Subjects may not be receiving any other investigational agents.
• Subjects with known untreated brain metastases. Subjects with known, treated brain metastases must be stable with no symptoms for four weeks.
• Subjects receiving enzyme-inducing antiseizure drugs ("EIASD").
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, 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.
• Pregnant women and breastfeeding should be discontinued.
• Absence of central venous access for administration of the study drug.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA): collaborator

Study Sites (1)

UT Southwestern Medical Center - Simmons Cancer Center

Dallas, Texas, 75390, United States

Location

Related Publications (1)

• Gerber DE, Beg MS, Fattah F, Frankel AE, Fatunde O, Arriaga Y, Dowell JE, Bisen A, Leff RD, Meek CC, Putnam WC, Kallem RR, Subramaniyan I, Dong Y, Bolluyt J, Sarode V, Luo X, Xie Y, Schwartz B, Boothman DA. Phase 1 study of ARQ 761, a beta-lapachone analogue that promotes NQO1-mediated programmed cancer cell necrosis. Br J Cancer. 2018 Oct;119(8):928-936. doi: 10.1038/s41416-018-0278-4. Epub 2018 Oct 15.

  PMID: 30318513 DERIVED

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

beta-lapachone; RE1-silencing transcription factor

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• David E Gerber, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2011
• First Posted: January 2, 2012
• Study Start: December 29, 2011
• Primary Completion: February 1, 2017
• Study Completion: March 1, 2019
• Last Updated: March 17, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)