Investigator-Initiated Study of Imipramine Hydrochloride and Lomustine in Recurrent Glioblastoma

NCT ID: NCT04863950

Last Updated: 2025-08-27

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-25
• Study Completion Date: 2026-11-30

Brief Summary

This study is designed as a single center, prospective, open label, single-arm therapeutic trial with both surgical and non-surgical cohorts.

Conditions

Glioblastoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Imipramine Hydrochloride/Lomustine

Group Type: EXPERIMENTAL

Lomustine

Intervention Type: DRUG

For surgical cohort patients, lomustine will be initiated (C1D1) within 6 weeks of surgery as soon as patient is deemed by the investigator (or designee) to be recovered enough for chemotherapy. Initiation of lomustine must be initiated within 6 weeks. If patient cannot be safely initiated on lomustine within this timeframe then they will be replaced.

For non-surgical cohort patients (the decision for surgery is made independent of study participation), lomustine will be initiated on C1D1.

For both cohorts, lomustine will be administered as 110 mg/m2 PO once every 6 weeks.

Imipramine Hydrochloride

Intervention Type: DRUG

For the surgical cohort, imipramine hydrochloride will be initiated within a minimum of 16 days to a maximum of 3 weeks prior to surgery. Imipramine hydrochloride will be administered as 50mg PO (oral) QHS (at bedtime) for 4 days followed by a dose increase (taper-up) of 50mg/day every fourth day to attain a maximum dose of 200mg/day in 16 days.

For non-surgical cohort patients (the decision for surgery is made independent of study participation), imipramine hydrochloride will be initiated on Cycle 1 Day 1. Imipramine hydrochloride will be administered as 50mg PO (oral) QHS (at bedtime) for 4 days followed by a dose increase (taper-up) of 50mg/day every fourth day, if tolerated, to attain a maximum dose of 200mg/day in 16 days.

Interventions

Lomustine

For surgical cohort patients, lomustine will be initiated (C1D1) within 6 weeks of surgery as soon as patient is deemed by the investigator (or designee) to be recovered enough for chemotherapy. Initiation of lomustine must be initiated within 6 weeks. If patient cannot be safely initiated on lomustine within this timeframe then they will be replaced.

For non-surgical cohort patients (the decision for surgery is made independent of study participation), lomustine will be initiated on C1D1.

For both cohorts, lomustine will be administered as 110 mg/m2 PO once every 6 weeks.

Intervention Type: DRUG

Imipramine Hydrochloride

For the surgical cohort, imipramine hydrochloride will be initiated within a minimum of 16 days to a maximum of 3 weeks prior to surgery. Imipramine hydrochloride will be administered as 50mg PO (oral) QHS (at bedtime) for 4 days followed by a dose increase (taper-up) of 50mg/day every fourth day to attain a maximum dose of 200mg/day in 16 days.

For non-surgical cohort patients (the decision for surgery is made independent of study participation), imipramine hydrochloride will be initiated on Cycle 1 Day 1. Imipramine hydrochloride will be administered as 50mg PO (oral) QHS (at bedtime) for 4 days followed by a dose increase (taper-up) of 50mg/day every fourth day, if tolerated, to attain a maximum dose of 200mg/day in 16 days.

Intervention Type: DRUG

Other Intervention Names

Gleostine; Trofranil

Eligibility Criteria

Inclusion Criteria

• The subject is at least 18 years of age
• The subject has the ability to understand the purposes and risks of the study and to have signed a written informed consent form approved by the investigator's IRB/Ethics Committee
• The subject has histologically confirmed glioblastoma
• The subject has progression following standard combined modality treatment with radiation and temozolomide chemotherapy
• The subject has an ECOG (Eastern Cooperative Oncology Group) performance status ≤ 2
• The subject has a life expectancy of at least 3 months
• The subject has acceptable liver function:
• Bilirubin ≤ 1.5 times upper limit of normal
• AST (aspartate aminotransferase) (SGOT) and ALT (alanine transaminase 0 (SGPT) ≤ 3.0 times upper limit of normal (ULN)
• The subject has acceptable renal function:
• Serum creatinine ≤ULN
• The subject has acceptable hematologic status (without hematologic support):
• ANC (absolute neutrophil count) ≥1500 cells/uL
• Platelet count ≥100,000/uL
• Hemoglobin ≥9.0 g/dL
• All women of childbearing potential (not surgically sterilized or at least 1 year post-menopausal) must have a negative serum pregnancy test. Additionally, male and female subjects must agree to use effective means of contraception (surgical sterilization or the use or barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an IUD) with their partner from entry into the study through 6 months after the last dose.

Exclusion Criteria

• The subject is receiving warfarin (or other coumarin derivatives) and is unable to switch to low molecular weight heparin (LMWH) before the first dose of study drug.
• The subject has evidence of acute intracranial or intratumoral hemorrhage either by MRI or computerized tomography (CT) scan. Subjects with resolving hemorrhage changes, punctate hemorrhage, or hemosiderin are eligible.
• The subject is unable to undergo MRI scan (eg, has pacemaker).
• The subject has received enzyme-inducing anti-epileptic agents within 14 days of study drug (eg, carbamazepine, phenytoin, phenobarbital, primidone).
• The subject has not recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grade ≤ 1 from AEs (except alopecia, anemia and lymphopenia) due to surgery, antineoplastic agents, investigational drugs, or other medications that were administered prior to study drug.
• The subject has evidence of wound dehiscence.
• The subject is pregnant or breast-feeding.
• The subject has a history of cardiac disease, including arrhythmia, conduction abnormality, congenital prolonged QT syndrome, myocardial infarction, unstable angina pectoris or congestive heart failure.
• A prolonged QTc rhythm noted during initial ECG >480 ms.
• The subject has serious intercurrent illness, such as:
• Hypertension (two or more blood pressure [BP] readings performed at screening of > 150 mmHg systolic or > 100 mmHg diastolic) despite optimal treatment

• Non-healing wound, ulcer, or bone fracture
• Untreated hypothyroidism
• Unhealed rectal or peri-rectal abscess
• Uncontrolled active infection
• Stroke, or transient ischemic attack within 6 months
• The subject has received any of the following prior anticancer therapy:

• Non-standard radiation therapy such as brachytherapy, systemic radioisotope therapy (RIT), or intra-operative radiotherapy (IORT). Note: stereotactic radiosurgery (SRS) is allowed
• Non-bevacizumab systemic therapy (including investigational agents and small- molecule kinase inhibitors) or non-cytotoxic hormonal therapy (eg, tamoxifen) within 7 days or 5 half-lives, whichever is shorter, prior to first dose of study drug
• Biologic agents (antibodies, immune modulators, vaccines, cytokines) within 21 days prior to first dose of study drug
• Nitrosoureas or mitomycin C within 42 days, or metronomic/protracted low-dose chemotherapy within 14 days, or other cytotoxic chemotherapy within 28 days, prior to first dose of study drug
• Prior treatment with carmustine wafers
• Any current psychosis, uncontrolled mood disorder (as assessed by investigator) or suicidal ideation. Additionally, current or history of bipolar disorder is excluded.
• Patients currently using SSRI, SNRI, MAO inhibitors, tramadol or trazodone who are unwilling to undergo taper.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The University of Texas Health Science Center at San Antonio

OTHER

Sponsor Role: lead

Responsible Party

William Kelly

Clinical Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

William Kelly, MD

Role: PRINCIPAL_INVESTIGATOR

The University of Texas Health Science Center - Mays Cancer Center

Locations

Mays Cancer Center, UT Health San Antonio

San Antonio, Texas, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Epp Goodwin

Role: CONTACT

goodwine@uthscsa.edu

210 450 5798

Maggie Tomasini

Role: CONTACT

tomasinim@uthscsa.edu

210 450 5962

Facility Contacts

Epp Goodwin

Role: primary

210-450-1000

Other Identifiers

CTMS# 20-0148

Identifier Type: -

Identifier Source: org_study_id