Study of CPI-0610 in Patients With Malignant Peripheral Nerve Sheath Tumors

• Status: Withdrawn
• Trial end date: 2018-05-17
• Target enrollment: 0
• Participant gender: All

Summary

Establish safety and toxicity profile and preliminary response rate of CPI-0610 in MPNST patients and correlate response with pharmacodynamics markers and BET inhibition.

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

Details

• Lead Sponsor: University of Texas Southwestern Medical Center

Criteria

Inclusion Criteria:

1. Age >18 years

2. Must have histologically confirmed diagnosis of MPNST

3. Must have measurable disease by CT scan or MRI

4. Eastern Cooperative Oncology Group - ECOG performance status <2

5. Adequate organ and marrow function as defined below:

• absolute neutrophil count greater than or equal to 1,000/mcL

• platelets greater than or equal to 75,000/mcL

• total bilirubin <2X normal institutional limits

• AST(SGOT)/ALT(SPGT) greater than or equal to 2.5 X institutional upper limit of normal

• creatinine <2X institutional upper limit of normal

6. Patients must have fully recovered from major surgery and from the acute toxic effects of prior chemotherapy and radiotherapy - residual grade 1 toxicity, e.g., grade 1 peripheral neuropathy and residual alopecia are allowed.

7. Female patients who are pre-menopausal or have experienced menopause for less than 2 years must have a negative serum pregnancy test <72 hours before starting study treatment. Male and female patients with reproductive potential must agree to use appropriate contraceptive methods while on study and for 3 months after the last dose of CPI-0610. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

Exclusion Criteria:

1. Current infection with HIV, hepatitis B or hepatitis C. Patients will have serologic testing performed during screening for HIV and hepatitis B and C. Any serologic results suggestive of an ongoing viral infection will be further investigated as necessary to clarify the patient's status.

2. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of CPI-0610, including any unresolved nausea, vomiting, or diarrhea that is CTCAE grade >1.

3. Impaired cardiac function or clinically significant cardiac diseases, including any of the following:

Acute myocardial infarction or angina pectoris <6 months prior to starting study drug

4. Uncontrolled cardiac arrhythmia - patients with rate-controlled atrial fibrillation are not excluded.

5. A past medical history of other clinically significant cardiovascular disease - e.g., uncontrolled hypertension, history of labile hypertension or history of poor compliance with an antihypertensive regimen.

6. Any other concurrent severe and/or uncontrolled concomitant medical condition that could compromise participation in the study - e.g., clinically significant pulmonary disease, clinically significant neurological disorder, active or uncontrolled infection.

7. Systemic anti-cancer treatment or radiotherapy less than 2 weeks before the first dose of CPI-0610.

8. Treatment with an investigational small molecule less than 2 weeks before the first dose of CPI-0610.

9. Immunosuppressive treatment that cannot be discontinued prior to study entry and for the duration of the study. Immunosuppressive treatment should be discontinued for at least 1 week prior to start of the administration of CPI-0610. Oral prednisone at a dose of 10mg or less per day is allowed, as are other oral corticosteroids given at glucocorticoid-equivalent doses. Topical, nasal and inhaled corticosteroids are also allowed.

10. Pregnant or lactating women.

11. Women of child bearing potential and men with reproductive potential, if they are unwilling to use adequate contraception while on study therapy and for 3 months thereafter.

12. Use of strong CYP inhibitors or drugs that carry a definite risk of Torsades de Pointes.

13. Patients unwilling or unable to comply with the study protocol.