NK Cell Therapy + Temozolomide for Melanoma with Brain Metastasis

Recruiting in Palo Alto (17 mi)

Overseen by Kari L. Kendra

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Kari Kendra

Disqualifiers: Active infection, Hepatic disease, Renal disease, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing a combination of special immune cells and a cancer drug to treat patients with advanced melanoma that has spread to the brain. The immune cells aim to kill the cancer, and the drug helps stop its growth. A new treatment has shown effectiveness against advanced melanoma and brain involvement.

Will I have to stop taking my current medications?

The trial requires that you stop any anticancer treatments at least 4 weeks before joining. If you're taking steroids for brain swelling, you need to be on a stable dose, and higher doses must be approved by the study's principal investigator.

What data supports the effectiveness of the drug Temozolomide for treating melanoma with brain metastasis?

Research shows that Temozolomide, when used with other treatments like thalidomide and whole brain radiation therapy, can shrink brain metastases in patients with metastatic melanoma. It is effective because it can cross the blood-brain barrier, which many other drugs cannot do, and has shown positive results in clinical trials for brain metastases from various solid tumors. ^{1 2 3 4 5}

Is the combination of NK Cell Therapy and Temozolomide safe for humans?

Temozolomide has been studied for safety in various conditions, including brain metastases from lung cancer and melanoma, and is generally considered safe, though it may have side effects. The combination with NK Cell Therapy has not been specifically addressed in the provided studies, but Temozolomide alone has been used safely in heavily pre-treated patients. ^{1 2 6 7 8}

How is the NK Cell Therapy + Temozolomide treatment different for melanoma with brain metastasis?

This treatment is unique because it combines Natural Killer (NK) Cell Therapy, which uses immune cells to target cancer, with Temozolomide, a drug that can cross the blood-brain barrier to treat brain metastases. This combination aims to enhance the immune response against melanoma cells in the brain, offering a novel approach compared to standard treatments like radiation alone. ^{2 3 4 5 9}

Research Team

Kari L. Kendra

Principal Investigator

Ohio State University Comprehensive Cancer Center

Eligibility Criteria

This trial is for adults over 18 with stage IV melanoma that has spread to the brain. Participants must have finished any cancer treatments at least 4 weeks prior, have certain normal organ function tests, and no severe mental status changes or other serious medical conditions. Women of childbearing age and men who can father a child must use effective contraception.

Inclusion Criteria

I am not a candidate for precise, high-dose radiation therapy.

I have at least one brain tumor larger than 10 mm that is growing.

My melanoma is confirmed and has spread to other parts of my body.

Exclusion Criteria

Pregnant women, women who are likely to become pregnant or are breastfeeding

I do not have any severe illnesses like active infections or liver/kidney diseases.

I am mentally capable and have no major obstacles that would prevent me from following the study's requirements.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive UD TGFbetai NK cells intravenously over 30 minutes on day 1 and temozolomide orally daily on days 1-5. Treatment with UD TGFbetai NK cells repeats every 28 days for up to 3 cycles.

12 weeks

3 cycles of treatment, each lasting 28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment completion every 6 months for up to 5 years.

5 years

Follow-up visits every 6 months

Treatment Details

Interventions

• Natural Killer Cell Therapy (CAR T-cell Therapy)
• Temozolomide (Alkylating agents)

Trial Overview The trial is testing the safety and effectiveness of UD TGFbetai NK cell therapy combined with temozolomide in shrinking brain tumors caused by melanoma. It's exploring the best dose of these therapies in patients whose cancer has advanced despite previous treatments.

Participant Groups

Group I: Treatment (UD TGFbetai NK cells, temozolomide) Experimental Treatment 2 Interventions

Patients receive UD TGFbetai NK cells IV over 30 minutes on day 1 and temozolomide PO daily on days 1-5. Treatment with UD TGFbetai NK cells repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Cycles of temozolomide repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

Kari Kendra

Lead Sponsor

Trials

3

Recruited

50+

Findings from Research

In a phase II study involving 30 patients with brain metastases from non-small cell lung cancer (NSCLC), temozolomide (TMZ) was found to be an active and safe treatment option, with 10% of patients achieving an objective response, including two complete remissions.

No severe (grade 3 or 4) toxicities were reported, and all treatment-related adverse events were mild to moderate, indicating that TMZ can be administered without significant safety concerns in this heavily pre-treated patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral temozolomide in heavily pre-treated brain metastases from non-small cell lung cancer: phase II study. Giorgio, CG., Giuffrida, D., Pappalardo, A., et al.[2018]

Temozolomide is a chemotherapeutic agent that effectively crosses the blood-brain barrier and has shown a good safety profile in treating brain metastases from solid tumors, with clinical activity observed in heavily pretreated patients.

In a randomized phase II trial, temozolomide combined with radiation therapy resulted in a significantly higher objective response rate (96% vs. 67%) compared to radiation alone, particularly benefiting patients with newly diagnosed brain and lung metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide for treating brain metastases. Abrey, LE., Christodoulou, C.[2019]

Temozolomide, an oral chemotherapy drug, was found to be well tolerated in patients with brain metastases from metastatic melanoma, with only 3% of patients discontinuing treatment due to adverse effects.

In a study of 151 patients, temozolomide showed some efficacy, with 7% of previously untreated patients achieving an objective response and 29% having stable disease, although the median overall survival was 3.5 months for untreated patients and 2.2 months for those previously treated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide for the treatment of brain metastases associated with metastatic melanoma: a phase II study. Agarwala, SS., Kirkwood, JM., Gore, M., et al.[2018]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Oral temozolomide in heavily pre-treated brain metastases from non-small cell lung cancer: phase II study. [2018]

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

Temozolomide, thalidomide, and whole brain radiation therapy for patients with brain metastasis from metastatic melanoma: a phase II Cytokine Working Group study. [2018]

3. Spain pubmed.ncbi.nlm.nih.gov

[Temozolomide in patients with melanoma brain metastases treated with whole brain irradiation]. [2019]

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

Temozolomide for treating brain metastases. [2019]

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

Temozolomide in combination with docetaxel in patients with advanced melanoma: a phase II study of the Hellenic Cooperative Oncology Group. [2018]

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

NKG2D-Dependent Antitumor Effects of Chemotherapy and Radiotherapy against Glioblastoma. [2022]

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

Temozolomide induces the expression of the glioma Big Potassium (gBK) ion channel, while inhibiting fascin-1 expression: possible targets for glioma therapy. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Biochemical changes associated with a multidrug-resistant phenotype of a human glioma cell line with temozolomide-acquired resistance. [2022]

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

Temozolomide for the treatment of brain metastases associated with metastatic melanoma: a phase II study. [2018]