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

NCT04863950 | Recruiting Phase 2 FDA Drug

• 1 other identifier: CTMS# 20-0148
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  6 months

Study Arms (1)

Imipramine Hydrochloride/Lomustine

EXPERIMENTAL

Drug: Lomustine; Drug: Imipramine Hydrochloride

Interventions

Lomustine 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.

Also known as: Gleostine

Imipramine Hydrochloride/Lomustine

Imipramine Hydrochloride 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.

Also known as: Trofranil

Imipramine Hydrochloride/Lomustine

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead

Study Sites (1)

Mays Cancer Center, UT Health San Antonio

San Antonio, Texas, 78229, United States

RECRUITING

MeSH Terms

Conditions

Glioblastoma

Interventions

Lomustine; Imipramine

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds; Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• William Kelly, MD

  The University of Texas Health Science Center - Mays Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Epp Goodwin

CONTACT

210 450 5798; goodwine@uthscsa.edu

Maggie Tomasini

CONTACT

210 450 5962; tomasinim@uthscsa.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Investigator

Study Record Dates

• First Submitted: April 23, 2021
• First Posted: April 28, 2021
• Study Start: May 25, 2022
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: August 27, 2025

Record last verified: 2025-08

Locations

US (1)