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

  • STATUS
    Recruiting
  • End date
    Nov 1, 2024
  • participants needed
    47
  • sponsor
    Cornerstone Pharmaceuticals
Updated on 17 June 2022

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. 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.

Details
Condition Sarcoma, Clear Cell
Treatment CPI-613 + Hydroxychloroquine
Clinical Study IdentifierNCT04593758
SponsorCornerstone Pharmaceuticals
Last Modified on17 June 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

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 ≥12 (and at least 40 kg)
Karnofsky performance status ( > 60). For 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
Organ Function Requirements
of the study only. Patients in the phase 1 portion of the study with EWS will
Adequate bone marrow function defined as
have progressed after at least one prior-line of standard therapy and patients
For patients with solid tumors without known bone marrow involvement
with TRK fusion-positive tumors will have received prior therapy with a TRK
Peripheral absolute neutrophil count (ANC) ≥ 1,000/mm3
inhibitor. Patients must have relapsed or refractory clear cell sarcoma for
Platelet count ≥ 100,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
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
Adequate Renal Function Defined as
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)
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 90 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
• Creatinine clearance or radioisotope GFR ≥ 60mL/min/1.73 m2 or
stature data published by the CDC
Adequate Liver function is defined as
A serum creatinine based on age/gender as follows
Age Maximum Serum Creatinine (mg/dL) Male Female 10 to < 13 years 1.2 1.2 13 to < 16
Adequate Neurologic function is defined as
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
controlled
SGOT (AST) ≤2.5 times the ULN
Serum albumin ≥ 2 g/dL
• Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for
age
• SGPT (ALT) ≤2.5 times the ULN
Patients with seizure disorder may be enrolled if on anticonvulsants and well
Adequate Blood Pressure

Exclusion Criteria

For whom potentially curative anticancer therapy is available
Are pregnant or breast feeding
Patients who have an uncontrolled infection are not eligible
immunotherapy (antibody based) within 28 days of initiation of study therapy
Have received other chemotherapy within 14 days of initiation of study therapy or
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
Have immediately life-threatening, severe complications of malignancy such as
uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated
Patients with known G6PD deficiency
intravascular coagulation
Patients with known underlying retinal disease
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
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