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

The University of Texas System (UT)

Status and phase

Enrolling

Phase 2

Conditions

Glioblastoma

Treatments

Drug: Lomustine

Drug: Imipramine Hydrochloride

Study type

Interventional

Funder types

Other

Identifiers

NCT04863950

CTMS# 20-0148

Details and patient eligibility

About

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

Enrollment

25 estimated patients

Sex

All

Volunteers

No Healthy Volunteers

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.