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Solid TumorsPhase 1NCT01502800

Clinical Trial of ARQ 761 in Advanced Solid Tumors

A Phase 1 study testing ARQ 761, ARQ 761 Weekly Administration and Bi-Weekly Administration of ARQ 761 in people with Solid Tumors, run by University of Texas Southwestern Medical Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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 Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Solid Tumors
What is being tested?
ARQ 761, ARQ 761 Weekly Administration and Bi-Weekly Administration of ARQ 761
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
91 participants
Where
1 siteUnited States
Study dates
29 Dec 2011to Mar 2019
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • UT Southwestern Medical Center - Simmons Cancer Center

    Dallas, Texas, 75390

Other trials in United States

About this study

Official title: A Phase 1 Dose Escalation and Pharmacodynamic Study of ARQ 761 (Beta-Lapachone) in Adult Patients With Advanced Solid Tumors

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

Read the detailed description

This is an open label, dose escalation study of (-)-trans-3-(5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-1-yl)-4(1Hindol-3-yl) pyrrolidine-2,5-dione (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.

Conditions
Solid Tumors
Being tested
ARQ 761, ARQ 761 Weekly Administration, Bi-Weekly Administration of ARQ 761, Two Consecutive Weeks Administration of ARQ 761 with one week of rest
Keywords
Metastatic, Unresectable, Recurrent advanced
Medical subject headings
Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ARQ 761Drug

    Also called Beta-Lapachone

    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

  • ARQ 761 Weekly AdministrationDrug

    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.

  • Bi-Weekly Administration of ARQ 761Drug

    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.

  • Two Consecutive Weeks Administration of ARQ 761 with one week of restDrug

    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.

Study groups in NCT01502800
Study groupRoleWhat they receive
Part 1 (ARQ 761)ExperimentalARQ 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
Receives: Drug: ARQ 761
Part 2 Arm AExperimentalThe 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.
Receives: Drug: ARQ 761 Weekly Administration
Part 2 Arm BExperimentalARQ 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.
Receives: Drug: Bi-Weekly Administration of ARQ 761
Part 2 Arm CExperimentalARQ 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.
Receives: Drug: Two Consecutive Weeks Administration of ARQ 761 with one week of rest

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose (MTD)

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

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

Secondary outcomes (1)
  1. Pharmacokinetic profile of ARQ761

    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, Pharmacokinetics (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

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Jan 2012 (estimated)
  2. Study start29 Dec 2011
  3. Primary completionFeb 2017
  4. Study completionMar 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
91 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01502800
Sponsor's protocol ID
STU 042011-005
Other IDs
NCI-2011-03317
Status last verified
Mar 2020
First submitted
18 Oct 2011
Last updated
17 Mar 2020
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • 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.

    PubMed 30318513

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ARQ 761, ARQ 761 Weekly Administration and Bi-Weekly Administration of ARQ 761 in people with Solid Tumors, run by University of Texas Southwestern Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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).). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01502800, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2020.

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