Imipramine + Lomustine for Glioblastoma

Overseen By Epp Goodwin

Age: Any Age

Sex: Any

Trial Phase: Phase 2

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 All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 8-12 weeks

25 Participants Needed

What You Need to Know Before You Apply

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.

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. ^{1 2 3 4 5}

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. ^{2 3 6 7 8}

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 3 6 9 10}

Who Is on the Research Team?

William Kelly, MD

Principal Investigator

The University of Texas Health Science Center - Mays Cancer Center

Are You a Good Fit for This Trial?

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

I am not pregnant or have agreed to use effective birth control during and 6 months after the study.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Imipramine Hydrochloride
• Lomustine

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.

How Is the Trial Designed?

Group I: Imipramine Hydrochloride/Lomustine Experimental Treatment 2 Interventions

Imipramine Hydrochloride is already approved in United States, European Union, India, Brazil for the following indications:

Approved in United States as Tofranil for:

• Depression
• Anxiety
• Panic disorder

Approved in European Union as Tofranil for:

• Depression
• Anxiety
• Panic disorder

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+

Published Research Related to This Trial

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 involving 97 patients with malignant gliomas, temozolomide (TMZ) demonstrated a significantly higher response rate (35.71%) compared to lomustine (CCNU) (9.09%), indicating its greater efficacy in treating these aggressive brain tumors.

TMZ was found to have an acceptable safety profile, with common side effects being mild nausea and vomiting, suggesting it could be a preferred chemotherapy option for patients with refractory malignant brain gliomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A multicenter randomized controlled study of temozolomide in 97 patients with malignant brain glioma]. Qian, ZZ., Wang, HQ., Liu, XM., et al.[2018]

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 phase II trial involving 88 patients with recurrent glioblastoma, the addition of mebendazole (MBZ) to either temozolomide (TMZ) or lomustine (CCNU) did not improve overall survival (OS) beyond the pre-set benchmark of 55% at 9 months, with OS rates of 36.6% and 45% for the TMZ-MBZ and CCNU-MBZ arms, respectively.

The study found that while MBZ was well tolerated, with no treatment-related deaths, a significant portion of patients had poor performance status, which likely impacted the overall survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mebendazole plus lomustine or temozolomide in patients with recurrent glioblastoma: A randomised open-label phase II trial. Patil, VM., Menon, N., Chatterjee, A., et al.[2022]

In a study involving 35 patients with glioblastoma and anaplastic astrocytoma, the use of lomustin alongside hyperfractionated radiation therapy did not improve patient survival outcomes.

The treatment regimen included a total radiation dose of 65 Gy and lomustin administered in two stages, but ultimately, the combination did not enhance the effectiveness of the radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Results of hyperfractionated radiation therapy used in combination with lomustin in malignant gliomas of the brain]. Balkanov, AS., Makarenko, MF., Poliakov, PIu., et al.[2018]

In a study involving 15 patients who experienced severe nausea and vomiting from chemotherapy, the selective 5-HT3 receptor antagonist GR38032F effectively prevented vomiting, with only 1 patient experiencing nausea after treatment.

The treatment was well-tolerated, with minimal side effects reported, including mild sedation and dryness of the mouth, suggesting that GR38032F is a safe option for managing chemotherapy-induced nausea and vomiting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention of emesis in patients receiving cytotoxic drugs by GR38032F, a selective 5-HT3 receptor antagonist. Cunningham, D., Hawthorn, J., Pople, A., et al.[2019]

The ACNU chemotherapy regimen for malignant gliomas showed a 25% efficacy rate at a dose of 3 mg/kg, indicating a moderate response in treating this type of cancer.

While the treatment led to significant hematological side effects like leukopenia and thrombocytopenia, the use of G-CSF helped prevent neutropenia, and granisetron effectively managed nausea and vomiting associated with the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effective measures against side effects by increasing ACNU dose for malignant glioma: effects on digestive organs]. Numa, Y., Kasai, H., Imahori, T., et al.[2013]

In a study of 56 patients with newly diagnosed glioblastoma, treatment with radiotherapy and concurrent carboplatin plus teniposide followed by carmustine resulted in a median survival time of 12.5 months and a time to progression of 7.5 months.

The treatment was generally well-tolerated, with acceptable levels of toxicity, although 7.1% of patients experienced radiation necrosis, indicating that while the regimen is effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin and teniposide concurrent with radiotherapy in patients with glioblastoma multiforme: a phase II study. Brandes, AA., Rigon, A., Zampieri, P., et al.[2020]

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]

Citations

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]