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Sarcoma, Clear CellPhase 1/2NCT04593758

To Evaluate Maximally Tolerated Dose (MTD), Safety and Efficacy of CPI-613® (Devimistat) Plus Hydroxychloroquine in Patients With Relapsed or Refractory Clear Cell Sarcoma of Soft Tissue

A Phase 1/2 study testing CPI-613 + Hydroxychloroquine in people with Sarcoma, Clear Cell, run by Cornerstone Pharmaceuticals at 8 sites 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

The goal of this trial in Phase I is to determine the maximally tolerated dose (MTD) of hydroxychloroquine in combination with devimistat in patients with relapsed or refractory Clear Cell Sarcomas of the Soft Tissue and to describe the full toxicity profile. Read more about this study

Who is it for?
Ages 2 to 100 years
Conditions the study is for
Sarcoma, Clear Cell
What is being tested?
CPI-613 + Hydroxychloroquine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
8 sitesUnited States
Study dates
1 Sep 2021to 9 Mar 2023
Phase
Phase 1/2
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 2 to 100 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Able to understand and sign the consent. For patients <18yo, consent by a parent or guardian and appropriate assent by the patient will be obtained.
  • Patients must be age ≥ 2 years.
  • Karnofsky performance status ( > 60). For children and adolescent patients, Lansky performance status should be performed and converted to Karnofsky performance status utilizing the conversion table in Appendix IV: Performance Status Conversion Chart.
  • Presence of measurable disease per RECIST v1.1.
  • The phase I portion of the study (dose finding portion) will include patients with relapsed or refractory clear cell sarcoma and other fusion positive relapsed or refractory sarcomas as documented by official pathology report from the diagnosing institution or commercial laboratory.
  • Patients with Ewing Sarcoma (EWS) can also be enrolled in the phase I portion of the study only. Patients in the phase 1 portion of the study with EWS will have progressed after at least one prior-line of standard therapy and patients with TRK fusion-positive tumors will have received prior therapy with a TRK inhibitor. Patients must have relapsed or refractory clear cell sarcoma for the phase II portion of the study, defined as a recurrence of disease following or having failed to achieve a response to at least one prior therapy. Diagnosis of clear cell sarcoma must be documented by official pathology report from the diagnosing institution or commercial laboratory including presence of a characteristic translocation such as t(12;22)(q13;q12).
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  • Fertile men and their partners who are female of reproductive potential, must agree to abstain from sexual intercourse or to use two highly effective forms of contraception from the time of giving informed consent, during the treatment and for 180 days (females and males) following the last dose of devimistat. A highly effective form of contraception is defined as hormonal oral contraceptives, injectables, patches, intrauterine devices, doublebarrier method (e.g., synthetic condoms, diaphragm, or cervical cap with spermicidal foam, cream, or gel), or male partner sterilization.
  • Organ Function Requirements:
  • Adequate bone marrow function defined as:
  • For patients with solid tumors without known bone marrow involvement:
  • Peripheral absolute neutrophil count (ANC) ≥ 1,000/mm3
  • Platelet count ≥ 100,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
  • Adequate Renal Function Defined as:
  • Creatinine clearance or radioisotope GFR ≥ 60mL/min/1.73 m2 or
  • A serum creatinine based on age/gender as follows:
  • Age Maximum Serum Creatinine (mg/dL) Male Female 2 to < 6 years 0.8 0.8 6 to < 10 years 1.0 1.0 10 to < 13 years 1.2 1.2 13 to < 16 years 1.5 1.4
  • ≥ 16 years 1.7 1.4 The threshold creatinine values in this Table were derived from the Schwartz formula for estimating GFR utilizing child length and stature data published by the CDC.
  • Adequate Liver function is defined as:
  • Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age
  • SGPT (ALT) ≤2.5 times the ULN
  • SGOT (AST) ≤2.5 times the ULN
  • Serum albumin ≥ 2 g/dL
  • Adequate Neurologic function is defined as:
  • Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled.
  • Adequate Blood Pressure.

Who cannot join

  • Have received other chemotherapy within 14 days of initiation of study therapy or immunotherapy (antibody based) within 28 days of initiation of study therapy.
  • For whom potentially curative anticancer therapy is available.
  • Are pregnant or breast feeding.
  • Have known hypersensitivity to any of the components of devimistat or hydroxychloroquine.
  • Have any other medical or psychological condition, deemed by the physician to be likely to interfere with a subject's ability to sign informed consent, cooperate, or participate in the treatment.
  • Patients who have an uncontrolled infection are not eligible.
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  • Patients with known G6PD deficiency.
  • Patients with known underlying retinal disease.
  • Have immediately life-threatening, severe complications of malignancy such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation.
  • Are unable to take oral medication OR have malabsorption syndrome or any other uncontrolled gastrointestinal condition (eg, nausea, diarrhea, vomiting) that might impair the bioavailability of study treatment.
  • Use of high-risk QT-prolonging drugs and patients with a history of torsades de pointes.
  • Unresolved toxicity from prior therapy that has failed to resolve to CTCAE ≤ grade 1 or baseline toxicity with the exception of alopecia
  • History of unstable or deteriorating cardiovascular disease within the previous 6 months prior to screening including but not limited to the following: unstable angina or myocardial infarction, CVA/stroke, Congestive heart failure (New York Heart Association [NYHA] Class III or IV, or uncontrolled clinically significant arrhythmias.
  • Marked baseline prolongation of QT/QTc interval (repeated exhibition of a QTc interval >480 ms for both male and female patients)
  • Unwilling or unable to avoid the concomitant use of strong CYP3A4 inducers or inhibitors during study treatment.
  • Patients concomitantly on tamoxifen are excluded due to increased ocular toxicity with hydroxychloroquine

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • City of Hope

    Duarte, California, 91010

  • University of Kansas Medical Center

    Kansas City, Kansas, 66160

  • Vanderbilt University Medical Centrer

    Nashville, Tennessee, 37232

  • Clevland Clinic

    Ohio City, Ohio, 44195

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • Seattle Children's Hospital

    Seattle, Washington, 98105

  • Atrium Health Wake Forest Baptist

    Winston-Salem, North Carolina, 27109

Other trials in United States

About this study

Official title: A Phase I/II Open-Label Trial of CPI-613® (Devimistat) Plus Hydroxychloroquine to Evaluate Maximally Tolerated Dose (MTD), Safety and Efficacy in Patients With Relapsed or Refractory Clear Cell Sarcoma of Soft Tissue

The goal of this trial in Phase I is to determine the maximally tolerated dose (MTD) of hydroxychloroquine in combination with devimistat in patients with relapsed or refractory Clear Cell Sarcomas of the Soft Tissue and to describe the full toxicity profile. In Phase II, the goal is to evaluate the response rate [Complete Rate (CR) + Partial Rate (PR)] of the combination of devimistat and hydroxychloroquine in patients with relapse or refractory Clear Cell Sarcoma of the Soft Tissue and to evaluate the PK and PK/PD profiles for efficacy and safety of the combination of devimistat and hydroxychloroquine.

Being tested
CPI-613 + Hydroxychloroquine
Medical subject headings
Sarcoma, Clear Cell

What participants receive

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

  • CPI-613 + HydroxychloroquineDrug

    dosing regimen was 600mg hydroxychloroquine PO followed 2 hours later by 2,000 mg/m2 of CPI-613 by central IV infusion over 2 hours followed by 600 mg hydroxychloroquine PO 12 hours following the initial dose daily on days 1 through 5 of every 28 days.

    Starting dose of 80% of the maximum tolerated (MTD) identified in patients ≥ 45 kg for patients < 45 kg

Study groups in NCT04593758
Study groupRoleWhat they receive
CPI-613 + HydroxychloroquineExperimentaldosing regimen was 600mg hydroxychloroquine PO followed 2 hours later by 2,000 mg/m2 of CPI-613 by central IV infusion over 2 hours followed by 600 mg hydroxychloroquine PO 12 hours following the initial dose daily on days 1 through 5 of every 28 days.
Receives: Drug: CPI-613 + Hydroxychloroquine

What is being measured

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

  1. MTD (Phase I)

    To determine the maximally tolerated dose (MTD) of hydroxychloroquine in combination with devimistat in mg/m2 based on patient body weight in patients with relapsed or refractory fusion-positive sarcomas and relapsed or refractory clear cell sarcoma.

    Measured: 6 months

  2. Toxicity (Phase I)

    Dose-limiting toxicities assessed in order to be able to establish the maximum tolerable dose for the combination of CPI-613 and Hydroxychloroquine therapy. Using the descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 for adverse event reporting (Grade 1 (Mild) - 5 (Death) as well as expectedness (unexpected/expected) and attribution (definitely related to study treatment to unrelated to study treatment).

    Measured: 6 months

  3. ORR (Overall Response rate): CR +PR (Phase II)

    Overall response rate is defined as the proportion of patients who achieve a best overall response complete response or partial response during or following study treatment

    Measured: 12 months

Secondary outcomes (3)

  1. DOR (Duration of Response)

    It is the interval from date of initial documented response (CR or PR) to the first documented date of disease progression or death.

    Measured: 12 months

  2. PFS (Progression Free Survival)

    It is defined as the duration from the date of enrollment to the date of progressive disease or death from any cause.

    Measured: 12 months

  3. OS (Overall Survival)

    Defines as the time from randomization to the date of death due to any cause.

    Measured: 12 months

Timeline

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

  1. First posted20 Oct 2020
  2. Study start1 Sep 2021
  3. Primary completion9 Mar 2023
  4. Study completion9 Mar 2023

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04593758
Sponsor's protocol ID
CCS618
Status last verified
May 2023
First submitted
7 Oct 2020
Last updated
24 May 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing CPI-613 + Hydroxychloroquine in people with Sarcoma, Clear Cell, run by Cornerstone Pharmaceuticals at 8 sites 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 25 inclusion and 16 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 24 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

MTD (Phase I) (time frame: 6 months). The study lists 3 primary outcomes in all. 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 NCT04593758.

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 24 May 2023.

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