Study of Icapamespib (PU-AD) in Patients With Recurrent Malignant Glioma

• Status: Not yet recruiting
• Trial end date: 2022-08-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a 2-part multicenter Phase 1b study designed to test icapamespib in patients with recurrent brain lesions.

Part 1 of the trial will be a standard 3 by 3 dose escalation design where different doses are examined. Part 2 will be a dose expansion cohort to further evaluate the recommended Phase 2 dose (RP2D). The RP2D is defined as the dose level recommended for further clinical study, or the highest dose tested.

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

Details

• Lead Sponsor: Samus Therapeutics, Inc.

Criteria

Inclusion Criteria:

• • Have histologically confirmed World Health Organization IDH wild type GBM, or grade 3 IDH wildtype astrocytoma with molecular features of GBM, or grade 3 or 4, IDH mutant astrocytoma IDH grade III-IV malignant glioma (glioblastoma or gliosarcoma (Part 1) or IDH wild type GBM (Part 2).

• Subjects must be at 1st, 2nd or 3rd recurrence (Part 1) or 1st or 2nd recurrence (Part 2) and clinically require reoperation for tumor progression within 4 to 6 weeks (Part 2); Note: recurrence is defined as progression following initial therapy (i.e., radiation, chemotherapy, or radiation + chemotherapy); if the participant had a surgical resection for relapsed disease and no anti-tumor therapy instituted for up to 12 weeks, this is considered one recurrence.

• Measurable disease as defined by modified RANO (1 cm × 1 cm minimum dimensions, at least 12 weeks after final radiotherapy dose; if new disease is outside radiotherapy field, <12 weeks is acceptable).

• For Part 2, a subset of at least 5 subjects will have a clinical indication for surgery for recurrent disease.

For Part 2 subjects who will undergo surgery for recurrent disease, formalin-fixed archival slides of tumor tissue from the original resection must be available for review.

• Cranial MRI performed within 14 days prior to study entry.

• Age equal to or greater than 18 years and life expectancy > 10 weeks.

• Karnofsky performance status of >60.

• Adequate bone marrow, liver and renal functions (tests must be performed within 14 days prior to enrollment).The following laboratory values must be documented within 3 days prior to the first dose of study drug Absolute neutrophil count (ANC) ≥1.5 × 109/L Platelet count ≥100 × 109/L Estimated creatinine clearance (CrCl) >60 mL/min by Cockcroft-Gault formulation Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤1.5 × the upper limit of normal (ULN) Total bilirubin ≤1.5 × ULN (unless due to Gilbert's syndrome) Serum albumin ≥2.8 g/dL International normalized ratio (INR) <1.5 (except subjects maintained on anticoagulant medications)

• Negative serum or urine pregnancy test (females of childbearing potential only).

Male patients:

Male patients with female partners of childbearing potential are eligible to participate if they agree to ONE of the following methods of contraception from 21 days before the first dose of IMP through 4 months after the last dose of the IMP:

• Abstinence from penile-vaginal intercourse as their usual and preferred lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent

• Use of a male condom plus partner use of a contraceptive method with a failure rate of < 1% per year when having penile-vaginal intercourse with a woman of childbearing potential who is not currently pregnant.

In addition, male patients must refrain from donating sperm for the duration of the study and for 4 months after the last dose of the IMP.

Female patients:

A female patient is eligible to participate if she is not pregnant and/or breastfeeding. Females of childbearing potential must agree to use a highly effective method of contraception consistently and correctly during the Treatment Period and for at least 3 months after the last dose of IMP.

Highly effective methods of contraception include, combined hormonal (estrogen and progestogen containing) contraception, which may be oral, intravaginal, or transdermal, progestogen-only hormonal contraception associated with inhibition of ovulation, which may be oral, injectable, or implantable, placement of an intrauterine device, placement of an intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner and true sexual abstinence, if it is the chosen life style of the patient.

• Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only and the lactational amenorrhea method are not acceptable methods of contraception. Female condom and male condom should not be used together.

• Able and willing to give informed consent.

Exclusion Criteria:

• • Currently receiving any concomitant anti-cancer medication

• Prior treatment with Gliadel wafers.

• No radiation within 12 weeks of starting treatment.

• Has tumor localized primarily to the brainstem or spinal cord.

• A history of any other primary malignancy that has not been treated with curative intent and that has not been in complete remission for at least 2 years (exempt from the two year limit are non-melanoma skin cancer and cervical carcinoma in-situ on biopsy or a squamous intraepithelial lesion on PAP smear).

• Active infection requiring systemic treatment.

• Any significant medical illnesses or toxicities that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patients' ability to tolerate this therapy. Patients must not have any disease that will obscure toxicity or dangerously alter drug metabolism, e.g. congestive heart failure, moderate to severe liver and renal disease, other cancers.

• History of unstable angina, myocardial infarction, chronic heart failure (New York Heart Association Class III or IV) or clinically significant conduction abnormalities (e.g., unstable atrial fibrillation) within 1 year prior to Screening

• QTcF interval on Screening Visit ECG or on average of triplicate Baseline Visit ECGs > 450 milliseconds (msec) for males or >470 msec for females (except when QT prolongation is associated with right or left bundle branch block, in which case enrollment is allowed).

• Has active ocular condition unrelated to primary intracranial pathology, that in the opinion of the investigator, may alter visual acuity during the course of the study.

• The need for concomitant use of long-acting gastric pH elevating agents (proton pump inhibitors or H2-receptor antagonists) at study entry and during the study (note: gastric locally-acting antacids may be allowed if administered >2 hours before or after dosing).

The need for concomitant use of any drugs that are sensitive substrates of CYP 450 isozymes (see Appendix 1 Table 1) with narrow therapeutic index for at least 7 days prior to administration of the first dose of IMP and throughout the study.

The need for concomitant use of any drugs that are strong inhibitors or inducers of cytochrome (CYP) 450 isozymes (see Appendix 1 Table 2) at least 7 days prior to administration of the first dose of IMP and throughout the study.

Has taken other investigational drugs or participated in any clinical study within 30 days or 5 half-lives (if known) of the investigational drug, whichever is longer, prior to first dose of IMP in this study or is currently participating in another clinical study.

Have received temozolomide within 4 weeks, or lomustine within 6 weeks, of the first dose of icapamespib.

Other unspecified reasons that, in the opinion of the investigator or Samus and/or its delegated medical monitor, place the subject at risk or make the subject unsuitable for the study or unable or unwilling to comply with the requirements of the study Female subject of childbearing potential with positive pregnancy test or who is lactating History or presence of conditions, which in the judgment of the investigator, are known to interfere with the absorption distribution, metabolism or excretion of drugs, such as prior surgery or gastrointestinal dysfunction that may affect drug absorption (e.g., gastric bypass surgery, gastrectomy) Prior exposure to icapamespib or other HSP90 inhibitors