Using Imipramine and Lomustine to treat recurrent glioblastoma

A Phase II, Investigator-Initiated Study of Imipramine Hydrochloride and Lomustine in Recurrent Glioblastoma

This study is testing whether a combination of Imipramine and Lomustine can help people with recurrent glioblastoma whose tumors have continued to grow after other treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 25 (estimated)
• Sex: All
• Sponsor: The University of Texas Health Science Center at San Antonio (Academic / other)
• Drugs / interventions: bevacizumab, chemotherapy, radiation
• Locations: 1 site (San Antonio, Texas)
• Trial ID: NCT04863950 on ClinicalTrials.gov

What this trial studies

This interventional study is a single-center, prospective, open-label, single-arm trial aimed at evaluating the effectiveness of Imipramine Hydrochloride and Lomustine in patients with recurrent glioblastoma. Participants will be enrolled into surgical and non-surgical cohorts, and the study will assess the treatment's impact on tumor progression following standard therapies. The trial will include patients who have histologically confirmed glioblastoma and have experienced progression after prior treatments.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with histologically confirmed recurrent glioblastoma who have progressed after standard treatment.

Not a fit: Patients with glioblastoma who have not undergone standard treatment or have a poor performance status may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with recurrent glioblastoma.

How similar studies have performed: While this approach is novel in combining Imipramine with Lomustine for glioblastoma, similar studies have shown promise in targeting recurrent tumors with alternative therapies.

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.

Where this trial is running

San Antonio, Texas

• Mays Cancer Center, UT Health San Antonio — San Antonio, Texas, United States (Recruiting)

Study contacts

• Principal investigator: William Kelly, MD — The University of Texas Health Science Center - Mays Cancer Center
• Study coordinator: Epp Goodwin

Conditions Glioblastoma