Imipramine + Lomustine for Glioblastoma

Recruiting in Palo Alto (17 mi)

Overseen by William Kelly, MD

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: The University of Texas Health Science Center at San Antonio

Must not be taking: Warfarin, Enzyme-inducing antiepileptics, SSRIs, others

Disqualifiers: Cardiac disease, Hypertension, Infection, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing both surgical and non-surgical treatments to see how well they work for patients who need these types of interventions.

Will I have to stop taking my current medications?

If you are currently using SSRIs, SNRIs, MAO inhibitors, tramadol, or trazodone, you will need to taper off these medications before participating in the trial. Additionally, if you are on warfarin, you must switch to low molecular weight heparin before starting the study.

What data supports the effectiveness of the drug combination Imipramine and Lomustine for treating glioblastoma?

Research shows that lomustine, a component of the treatment, is effective in treating glioblastoma when used with other drugs like temozolomide and radiotherapy, improving long-term survival in patients. ^{1 2 3 4 5}

Is the combination of Imipramine and Lomustine generally safe for humans?

Lomustine has been used in combination with other treatments for brain tumors, and common side effects include changes in blood cell counts, nausea, and vomiting. These side effects can sometimes be managed with additional medications. ^{2 3 6 7 8}

How is the drug combination of Imipramine and Lomustine unique for treating glioblastoma?

The combination of Imipramine (an antidepressant) and Lomustine (a chemotherapy drug) for glioblastoma is unique because it pairs a drug typically used for depression with a chemotherapy agent, potentially offering a novel approach to treatment. This combination is different from standard treatments that usually involve other chemotherapy drugs like temozolomide. ^{1 3 6 9 10}

Research Team

William Kelly, MD

Principal Investigator

The University of Texas Health Science Center - Mays Cancer Center

Eligibility Criteria

Adults with confirmed glioblastoma who've had prior standard treatment and are now seeing progression. They must be in relatively good health (ECOG ≤ 2), have a life expectancy over 3 months, and proper organ function. Participants need to agree to contraception use and cannot be pregnant or breastfeeding. Exclusions include those unable to undergo MRI, recent users of certain anti-epileptic drugs, individuals with serious illnesses like uncontrolled hypertension or infections, history of cardiac disease, or those on specific medications.

Inclusion Criteria

My diagnosis is glioblastoma confirmed by tissue analysis.

I am 18 years old or older.

I understand the study's risks and goals and have signed the consent form.

Exclusion Criteria

My surgical wound has reopened.

I have had a recent brain bleed or tumor bleed, confirmed by MRI or CT scan.

I do not have serious ongoing health issues like uncontrolled high blood pressure, non-healing wounds, untreated thyroid problems, recent strokes, or active infections.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Imipramine Hydrochloride and Lomustine for recurrent glioblastoma

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Imipramine Hydrochloride (Tricyclic Antidepressant)
• Lomustine (Alkylating Agent)

Trial Overview The trial is testing the combination of Imipramine Hydrochloride and Lomustine in patients with recurrent glioblastoma. It's an open-label study meaning everyone knows what treatment they're getting. There are two groups: one undergoing surgery plus the drug therapy and another just receiving the drug therapy without surgery.

Participant Groups

Group I: Imipramine Hydrochloride/Lomustine Experimental Treatment 2 Interventions

Imipramine Hydrochloride is already approved in India, Brazil for the following indications:

Approved in India as Tofranil for:

• Depression
• Anxiety
• Panic disorder

Approved in Brazil as Tofranil for:

• Depression
• Anxiety
• Panic disorder

Who Is Running the Clinical Trial?

The University of Texas Health Science Center at San Antonio

Lead Sponsor

Trials

486

Recruited

92,500+

Dr. Andrew Masica

The University of Texas Health Science Center at San Antonio

Chief Medical Officer

MD from Indiana University School of Medicine

Dr. Taylor Eighmy

The University of Texas Health Science Center at San Antonio

Acting President

PhD in Civil Engineering from the University of New Hampshire

Findings from Research

In a study of 39 patients with newly diagnosed glioblastoma, the combination of radiotherapy and chemotherapy (lomustine and temozolomide) resulted in a median overall survival of 23.1 months, with 47.4% of patients surviving for 2 years and 18.5% for 4 years.

Patients receiving an intensified dose of chemotherapy showed significantly higher survival rates compared to those on standard doses, with some patients in the intensified group surviving over 56 months, although this came with a higher risk of severe hematotoxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term survival of patients with glioblastoma treated with radiotherapy and lomustine plus temozolomide. Glas, M., Happold, C., Rieger, J., et al.[2022]

In a study of 31 adult patients with newly diagnosed glioblastoma, the combination of lomustine, temozolomide (TMZ), and involved-field radiotherapy showed promising efficacy, with a median overall survival time of 22.6 months and a 2-year survival rate of 44.7%.

The treatment had acceptable toxicity levels, with 16% of patients experiencing severe hematotoxicity, and the presence of MGMT gene-promoter methylation in tumors was linked to longer progression-free survival and overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of lomustine plus temozolomide chemotherapy in addition to radiotherapy in newly diagnosed glioblastoma: UKT-03. Herrlinger, U., Rieger, J., Koch, D., et al.[2018]

Nitrosoureas, such as lomustine, carmustine, and fotemustine, are among the most effective treatments for high-grade gliomas and glioblastoma, highlighting their importance in cancer therapy.

Due to their toxicity and the introduction of temozolomide, nitrosoureas are now primarily used for recurrent cases of gliomas, indicating a shift in their clinical application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nitrosoureas in the Management of Malignant Gliomas. Brandes, AA., Bartolotti, M., Tosoni, A., et al.[2018]

In a study involving 362 patients with malignant glioma, the combination of ACNU plus VM26 showed a median survival of 17.3 months for glioblastoma and 60 months for anaplastic glioma, indicating promising outcomes compared to historical data.

The ACNU plus Ara-C treatment resulted in more hematologic toxicity, suggesting that ACNU plus VM26 may be a safer option for patients, warranting further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuro-Oncology Working Group 01 trial of nimustine plus teniposide versus nimustine plus cytarabine chemotherapy in addition to involved-field radiotherapy in the first-line treatment of malignant glioma. Weller, M., Müller, B., Koch, R., et al.[2013]

References

1. United States pubmed.ncbi.nlm.nih.gov

Long-term survival of patients with glioblastoma treated with radiotherapy and lomustine plus temozolomide. [2022]

2. China pubmed.ncbi.nlm.nih.gov

[A multicenter randomized controlled study of temozolomide in 97 patients with malignant brain glioma]. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Phase II trial of lomustine plus temozolomide chemotherapy in addition to radiotherapy in newly diagnosed glioblastoma: UKT-03. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Nitrosoureas in the Management of Malignant Gliomas. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Mebendazole plus lomustine or temozolomide in patients with recurrent glioblastoma: A randomised open-label phase II trial. [2022]

6. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Results of hyperfractionated radiation therapy used in combination with lomustin in malignant gliomas of the brain]. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Prevention of emesis in patients receiving cytotoxic drugs by GR38032F, a selective 5-HT3 receptor antagonist. [2019]

8. Japan pubmed.ncbi.nlm.nih.gov

[Effective measures against side effects by increasing ACNU dose for malignant glioma: effects on digestive organs]. [2013]

9. United States pubmed.ncbi.nlm.nih.gov

Carboplatin and teniposide concurrent with radiotherapy in patients with glioblastoma multiforme: a phase II study. [2020]

10. United States pubmed.ncbi.nlm.nih.gov

Neuro-Oncology Working Group 01 trial of nimustine plus teniposide versus nimustine plus cytarabine chemotherapy in addition to involved-field radiotherapy in the first-line treatment of malignant glioma. [2013]