Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at San Diego, California and other locations
Dates
study started
estimated completion
Principal Investigator
by David Piccioni, MD

Description

Summary

This is an open-label, multicenter, randomized, parallel, 2-arm, efficacy and safety study. Patients with GBM after failure of standard first line therapy will be randomized in a 2:1 ratio to receive berubicin or lomustine for the evaluation of OS. Additional endpoints will include response and progression outcomes evaluated by a blinded central reviewer for each patient according to RANO criteria. A pre-planned, non-binding futility analysis will be performed after approximately 30 to 50% of all planned patients have completed the primary endpoint at 6 months. This review will include additional evaluation of safety as well as secondary efficacy endpoints. Enrollment will not be paused during this interim analysis.

Official Title

A Multicenter, Open-Label Study With a Randomized Control Arm of the Efficacy, Safety, and Pharmacokinetics of Intravenously Infused Berubicin in Adult Patients With Recurrent Glioblastoma Multiforme (WHO Grade IV) After Failure of Standard First Line Therapy

Details

Berubicin is one of the first anthracyclines that crosses the blood brain barrier and overcomes drug resistance (i.e. it is not a substrate for multi-drug resistant/breast cancer resistant transporters). A Phase 1 clinical trial of berubicin in patients with primary CNS malignancies demonstrated a durable response (one subject alive 13+ years) as well as stable disease in heavily pretreated patients. Therefore, this phase 2 study is designed to further evaluate Berubicin's activity in patients with rGBM after treatment with standard of care.

Keywords

Glioblastoma Multiforme, Adult Glioblastoma Multiforme Glioblastoma Brain Cancer Brain Tumor Lomustine Berubicin

Eligibility

For people ages 18 years and up

Patients will be eligible for the study if they meet all of the following inclusion criteria and none of the exclusion criteria.

Inclusion criteria

  1. Written informed consent prior to any study-related procedure, and willing and able to comply with the protocol and aware of the investigational nature of this study.
  2. At least 18 years of age.
  3. A confirmed GBM diagnosis must be based on local review of tumor tissue from the initial biopsy, surgery, or re-resection. A formal pathology report confirming GBM is acceptable. It is not a requirement for slides to be sent to a central reviewer.
  4. Recurrent GBM as evaluated by RANO criteria, confirmed by central review, as follows: Measurable disease is required with documented unequivocal evidence of tumor recurrence or progression following prior therapy (ie, 25% increase in the sum of the products of perpendicular diameters of the contrast-enhancing lesions while on stable or increasing doses of corticosteroids) as documented by the investigator.
  5. The tumor is localized supratentorially.
  6. The lesion (or sum of lesions) does not exceed 50 cm3 in volume.
  7. MGMT methylation status must be available; results of routinely used methods for MGMT methylation testing (eg, methylation-specific polymerase chain reaction or quantitative polymerase chain reaction) are acceptable.
  8. No more than 1 prior line of treatment (eg, surgery followed by radiation with concomitant chemotherapy, followed by adjuvant chemotherapy is considered as 1 line of treatment). A second debulking surgery during the first line treatment is acceptable. In addition, treatment with tumor treating fields (TTFields; Optune) is acceptable if provided as first line therapy.
  9. Recovery from toxicity/side effects of all prior therapy to Grade 1 or less, subject to the investigator's discretion, except for alopecia; the following time intervals from previous treatments are required to be eligible:
  10. Twelve weeks from the completion of radiation (to reduce risk of pseudoprogression), unless progression is confirmed by biopsy
  11. 4 weeks from the end of any previous chemotherapy or 6 weeks after the end of treatment with nitrosoureas
  12. 4 weeks from the end of any TTFields treatment
  13. 4 weeks from any major surgery (maximal debulking surgery, either gross total resection or partial resection) or significant traumatic injury, and any surgery incisions or wounds must be completely healed
  14. . A stable or decreasing dose of corticosteroids (or none) for brain edema for at least 5 days prior to baseline MRI and enrollment in the study.
  15. . Immunosuppressive therapies allowed include the use of topical, inhalational, ophthalmic, or intra-articular glucocorticoids, or the use of physiologic replacement doses of glucocorticoids.
  16. . Eligible for chemotherapy based on adequate bone marrow function and organ function within 2 weeks of study treatment as defined by the following laboratory guidelines, subject to the investigator's discretion:
  17. Hematopoietic function: total white blood cell count ≥3000/mm³, absolute neutrophil count ≥1500/mm³, platelet count ≥75,000/mm³, hemoglobin ≥10 g/dL
  18. Hepatic function: bilirubin ≤1.5 × the upper limit of normal (ULN) (excluding Gilberts Syndrome, for which bilirubin must be ≤4 × ULN); aspartate aminotransferase and alanine aminotransferase <3 × ULN, and alkaline phosphatase ≤2.5 × ULN
  19. Renal function: serum creatinine ≤1.5 × ULN or for patients with creatinine levels above the ULN, or estimated creatinine clearance of ≥60 mL/min/1.73 m2, calculated using the Cockcroft-Gault formula
  20. Activated partial thromboplastin time ≤1.5 × ULN
  21. . Female patients of childbearing potential, and male study patients and their sexual partners of childbearing potential must agree to practice a highly effective method of contraception beginning at least 28 days before the start of treatment until at least 6 months after the last dose of study drug.
  22. A woman of childbearing potential is defined as a woman who is not permanently sterilized or postmenopausal. Postmenopausal is defined as 12 months with no menses without an alternative medical cause.
  23. Women of childbearing potential must have a negative serum or urine pregnancy test.
  24. A highly effective method of birth control is defined as one which results in a low failure rate (ie, less than 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some intrauterine devices, sexual abstinence, or vasectomized partner. For patients using a hormonal contraceptive method, information regarding all medications being administered to the patient and their potential effect on the contraceptive should be addressed.
  25. . Patients with prior malignancies must be disease-free for ≥5 years. However, curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, breast, or bladder; or prostate cancer curatively treated at the time of screening is allowed.

Exclusion Criteria

  1. Unable or not willing to comply with the protocol regulations.
  2. Any additional concurrent radiation therapy or chemotherapy (including but not limited to temozolomide) for recurrent or progressive GBM after a first line treatment.
  3. Prior treatment with bevacizumab.
  4. Prior treatment with lomustine.
  5. Screening MRI showing a mass effect defined as significant compression of the ventricular system and/or a midline shift (≥10 mm, central MRI review).
  6. Any condition (medical, social, psychological) that would prevent adequate information and follow-up, including but not limited to clinically relevant psychiatric disorders, legal incapacity, dementia, or altered mental status.
  7. Presence of poorly controlled seizures, defined as occurring despite SOC or requiring hospitalization.
  8. Prior anthracycline cumulative dose more than 550 mg/m2.
  9. Heart disease:
  10. LVEF <50%
  11. Unstable angina
  12. Congestive heart failure with New York Heart Association classification of 3 or 4
  13. Patients with baseline QT/QTc interval >480 msec, a history of additional risk factors for torsades de pointes (eg, heart failure, hypokalemia, family history of long QT syndrome) and using concomitant medications that significantly prolong the QT/QTc interval
  14. History of myocardial infarction within 12 months of enrollment
  15. . Uncontrolled hypertension (systolic blood pressure [BP] >150 mmHg and/or diastolic BP >100 mmHg).
  16. . Known to be positive for hepatitis B virus surface antigen (HBsAg), hepatitis C virus (HCV), human immunodeficiency virus (HIV), COVID-19 (currently positive at time of screening), or any other acute viral, bacterial, or fungal infection (testing not required unless symptomatic or suspected disease).
  17. . Any other uncontrolled intercurrent medical conditions, including but not limited to diabetes mellitus or chronic obstructive pulmonary disease that have not been well controlled by medical management over the prior 3 months are ineligible unless approved by the sponsor.

Locations

  • University of Califonia San Diego Moores Cancer Center not yet accepting patients
    San Diego California 92093 United States
  • University of California Irvine not yet accepting patients
    Orange California 92868 United States

Lead Scientist at UCSD

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
CNS Pharmaceuticals, Inc.
ID
NCT04762069
Phase
Phase 2
Study Type
Interventional
Last Updated