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
• Trial end date: 2024-11-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Rafael Pharmaceuticals Inc.
• Treatments: Hydroxychloroquine

Criteria

Inclusion Criteria:

1. Able to understand and sign the consent.

2. Patients must be between 11-75 years old.

3. Karnofsky performance status of > 60 for patients < 18 years old.

4. ECOG (Eastern Cooperative Oncology Group) performance status 0 - 2 for patients ≥ 18 years old.

5. 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. 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.

6. 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, double barrier method (e.g., synthetic condoms, diaphragm, or cervical cap with spermicidal foam, cream, or gel), or male partner sterilization.

7. Organ Function Requirements:

Adequate bone marrow function defined as:

1. 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)

2. Patients with known bone marrow metastatic disease will be eligible for study provided they meet the specified blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity. If dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity.

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 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.

• Nervous system disorders resulting from prior therapy must be ≤ Grade 2.

Adequate Blood Pressure control is defined as:

• A blood pressure (BP) ≤ the 95th percentile for age, height, and gender and not receiving medication for treatment of hypertension.

Exclusion Criteria:

1. Have received other chemotherapy within 7 days of initiation of study therapy or immunotherapy (antibody based) within 28 days of initiation of study therapy.

2. For whom potentially curative anticancer therapy is available.

3. Are pregnant or breast feeding.

4. Have known hypersensitivity to any of the components of devimistat or hydroxychloroquine.

5. 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.

6. Patients who have an uncontrolled infection are not eligible.

7. Have immediately life-threatening, severe complications of malignancy such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation.

8. No marked baseline prolongation of QT/QTc interval (repeated exhibition of a QTc interval > 480 ms for both male and female patients).