Clinical Trial of ARQ 761 in Advanced Solid Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by University of Texas Southwestern Medical Center
Sponsor:
Collaborator:
ArQule
Information provided by (Responsible Party):
University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier:
NCT01502800
First received: October 18, 2011
Last updated: August 18, 2014
Last verified: August 2014
  Purpose

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


Condition Intervention Phase
Solid Tumors
Drug: ARQ 761
Drug: ARQ 761 Weekly Administration
Drug: Bi-Weekly Administration of ARQ 761
Drug: Two Consecutive Weeks Administration of ARQ 761 with one week of rest
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Dose Escalation and Pharmacodynamic Study of ARQ 761 (Beta-Lapachone) in Adult Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by University of Texas Southwestern Medical Center:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) [ Time Frame: Patients will receive an average of 4 cycles of ARQ 761 (corresponding with a treatment cycle of 16 weeks). ] [ Designated as safety issue: Yes ]
    To determine the recommended Phase 2 dose (RP2D) of ARQ 761 administered intravenously.


Secondary Outcome Measures:
  • Pharmacokinetic profile of ARQ761 [ Time Frame: Samples will be drawn from each subject during first and fourth infusion of study drug ] [ Designated as safety issue: Yes ]
    Serial venous blood samples will be drawn from each subject during first and fourth infusion of study drug to determine the plasma levels of ARQ761.If the same dose is not administered for the first and fourth infusion of study drug, PK samples will only be collected after the first dose. PK samples to be collected at pre-infusion, 15min,30min, 55min (5 mins before end of infusion), 75 min, 2,4,6,h post infusion, 24h, 48h, and 168h


Estimated Enrollment: 30
Study Start Date: December 2011
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1 (ARQ 761)

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 4 weeks which completes 1 cycle (28 days). The total infusion time will be one (1) hour.

The beginning dose level will be 195 mg/m2 as long as most patients tolerate the lower doses without suffering from high grade risks the dose amount will increase until the maximum tolerated dose is defined.

Below is the seven dose levels that may be administered to you based on your tolerance of the ARQ 761 and if you meet the clinical criteria for continuance.

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
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
Other Name: Beta-Lapachone
Experimental: Part 2 Arm A-Weekly Administration of ARQ 761

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.

Drug: ARQ 761 Weekly Administration

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.

Experimental: Part 2 Arm B-Bi-Weekly Administration of ARG 761

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.

Drug: Bi-Weekly Administration of ARQ 761

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.

Experimental: Part 2 Arm C-Two Consecutive Weeks Administration of ARQ 761

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.

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

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.


Detailed Description:

This is an open label, dose escalation study of ARQ 761. Drug administration regimen was designed in two parts.

Part I is a single-arm, non-randomized dose-escalation study. Part II is a multi-arm, randomized dose-escalation study. It is designed to establish the clinical tolerability and MTD of ARQ 761 and a recommended Phase 2 dose (RP2D). This is the first-in-human study with ARQ 761.

PART I ARQ 761 will be administered intravenously at a starting dose of 195 mg/m2 IV once weekly. A cycle for any patient already enrolled will consist of weekly administration of ARQ 761 with cycles repeated every 4 weeks (28 days).

PART II Alternate dosing regimen of ARQ 761 will be evaluated at a starting dose of 390 mg/m2. ARQ 761 will be administered intravenously at the assigned duration (2 h or 3 h) weekly, biweekly or for two consecutive weeks followed by one week of rest. Patient will be randomized to Arm A, B or C after enrollment.

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 be considered. Patients enrolled and assessed for dose limiting toxicities (DLTs) will be eligible for intra-patient dose escalation.

Pharmacokinetic assessments will be performed on the first and the forth infusion days following the different regimen to maintain continuity among all treatment groups. Safety and tolerability of ARQ 761 will be assessed for the duration of study treatment. Evaluation of potential anti-tumor activity of ARQ 761 will be performed at regular intervals while patients remain on study. Dose escalation of ARQ 761 will proceed until the maximum tolerated dose or recommended Phase 2 dose is reached.

Intra-patient escalation from lower dose levels to successfully administered dose levels will be allowed. In order for patients at lower dose levels to be eligible for dose escalation, they must tolerate therapy without experiencing any DLT. In addition, prior to escalation, a complete cohort of three patients must have completed two cycles of therapy at the higher dose level without experiencing any DLTs. Patients receiving doses of ARQ 761 may be escalated a maximum of two times to the next consecutive cohorts.

Subjects will be enrolled according to a 3+3 dose escalation scheme. Treatment will be staggered such that the first patient treated at each dose level will receive his or her initial infusion at least 1 week prior to subsequent patients in the same cohort. At least 3 patients within a dose cohort must complete the first cycle of therapy prior to enrolling subjects at the next dose level.

  Eligibility

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

Inclusion Criteria:

  1. 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.
  2. 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.

  3. Measurable disease is not required, but will be evaluated in each subject when possible.
  4. Age ≥18 years
  5. ECOG performance status ≤ 1
  6. Life expectancy ≥ three months.
  7. Central venous access, such as a Portacath or Hickman Line.
  8. Pretreatment clinical laboratory parameters within 14 days
  9. Availability of 10 unstained slides or paraffin-embedded tissue block from archived tumor specimen.
  10. 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.

Exclusion Criteria:

  1. Subjects who have had cytotoxic chemotherapy or treatment with monoclonal antibodies within 4 weeks, radiotherapy within 3 weeks, or other molecular targeted therapies.
  2. Subjects may not be receiving any other investigational agents.
  3. Subjects with known untreated brain metastases. Subjects with known, treated brain metastases must be stable with no symptoms for four weeks.
  4. Subjects receiving enzyme-inducing antiseizure drugs ("EIASD").
  5. 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.
  6. Pregnant women and breastfeeding should be discontinued.
  7. Absence of central venous access for administration of the study drug.
  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: NCT01502800

Contacts
Contact: David E Gerber, MD 214-648-4180 david.gerber@utsouthwestern.edu
Contact: Melana Lindsey, MHSA 2146487094 melana.Lindsey@utsouthwestern.edu

Locations
United States, Texas
UT Southwestern Medical Center - Simmons Cancer Center Recruiting
Dallas, Texas, United States, 75390
Principal Investigator: David E Gerber, MD         
Sponsors and Collaborators
University of Texas Southwestern Medical Center
ArQule
Investigators
Principal Investigator: David E Gerber, MD University of Texas Southwestern Medical Center
  More Information

No publications provided

Responsible Party: University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT01502800     History of Changes
Other Study ID Numbers: 042011-005, NCI-2011-03317
Study First Received: October 18, 2011
Last Updated: August 18, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Texas Southwestern Medical Center:
Metastatic
Unresectable
Recurrent advanced

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

ClinicalTrials.gov processed this record on October 30, 2014