Liposomal Curcumin + RT/TMZ for Brain Tumor

Recruiting at 1 trial location

Overseen By Michelle Comas

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: SignPath Pharma, Inc.

Must be taking: Temozolomide

Must not be taking: Investigational agents

Disqualifiers: Concurrent cancer, Active infection, others

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

Compensation: Varies

Number of Visits: 1

Duration: 34 weeks

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new treatment combining a special form of curcumin with radiation and chemotherapy for patients with aggressive brain tumors. The goal is to improve curcumin absorption and enhance the effects of standard treatments.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are taking a medication that may increase the risk of hemolysis (breakdown of red blood cells), you may not be eligible to participate.

What data supports the effectiveness of the drug Liposomal Curcumin + RT/TMZ for brain tumors?

Research shows that Temozolomide (TMZ), when used with radiation therapy, improves survival in patients with glioblastoma (a type of brain tumor) and is effective for various brain tumors. It can penetrate the brain effectively, making it a valuable part of treatment for brain tumors. ^{1 2 3 4 5}

Is the combination of Liposomal Curcumin and Temozolomide generally safe for humans?

Temozolomide (TMZ) is generally well tolerated and safe, with common side effects like fatigue, nausea, and low blood cell counts. However, rare but serious side effects such as severe blood disorders and liver damage have been reported. ^{5 6 7 8 9}

What makes the Liposomal Curcumin + RT/TMZ treatment unique for brain tumors?

This treatment is unique because it combines liposomal curcumin, which may enhance the effects of traditional therapies, with standard treatments like radiotherapy and temozolomide (a chemotherapy drug). The use of liposomal curcumin could potentially improve the delivery and effectiveness of the treatment compared to using radiotherapy and temozolomide alone. ^{2 7 8 10 11}

Research Team

Matthias Holdhoff, MD

Principal Investigator

Johns Hopkins University

Peter Sordillo, MD, PhD

Principal Investigator

SignPath Pharma

Eligibility Criteria

Adults over 18 with newly diagnosed High-Grade Gliomas, including GBM and other types, suitable for RT/TMZ treatment. Must have good organ function, not be pregnant or breastfeeding, no recent heart issues or active infections requiring antibiotics. HIV-positive patients can join if undetectable viral load. Participants must agree to use contraception.

Inclusion Criteria

Adequate organ and marrow function defined as: Hgb > 9 g/dL, ANC ≥ 1500/µL, Platelet count ≥ 100,000/µL, Total bilirubin ≤ 1.5 * institutional ULN, AST and ALT ≤ 3 * institutional ULN, Creatinine ≤ 1.5 * institutional ULN OR Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 unless data exist supporting safe use at lower values of renal function, but eGFR must be ≥ 30 mL/min/1.73 m2, Patients with human immunodeficiency virus (HIV) who are on effective antiretroviral therapy are eligible if the viral load was assessed as undetectable within 6 months prior to baseline, Women: WOCBP must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of study participation, Men: must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 4 months after completion of LC administration

I have a high-grade glioma brain tumor suitable for radiation and chemotherapy treatment.

I am scheduled for 6 weeks of treatment with TMZ and radiation.

Exclusion Criteria

I still have side effects from cancer treatment, except for hair loss.

Receiving any other investigational agent

I have not had treatment for any cancer other than skin cancer in the last 2 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive Liposomal Curcumin (LC) in combination with radiotherapy (RT) and Temozolomide (TMZ) for a minimum of 34 weeks

34 weeks

Weekly visits for IV infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment, including overall survival (OS) and progression-free survival (PFS)

Ongoing

Regular phone or clinic follow-up

Dose Escalation

Dose finding using a time-to-event Bayesian optimal interval (TITE-BOIN) rule-based schema to determine the maximum tolerated dose (MTD) of LC

10 weeks

Treatment Details

Interventions

• Liposomal Curcumin
• Radiotherapy
• Temozolomide

Trial Overview The trial is testing the safety and effectiveness of Liposomal Curcumin (LC) when used alongside standard radiotherapy (RT) and Temozolomide (TMZ). The study will observe how well patients tolerate this combination therapy during different treatment periods: adjuvant, post-CRT, and concurrent CRT.

Participant Groups

Group I: Tolerability, Safety, and Efficacy of LC in Combination with RT and TMZ Experimental Treatment 4 Interventions

Define the MTD/recommended Phase 2 dose (RP2D) of LC, administered IV weekly in combination with standard CRT (60 Gy in 30-33 fractions M-F, and daily oral TMZ 75 mg/m2), in patients with high grade malignant gliomas. This study seeks the MTD/RP2D of LC when added to TMZ during concurrent RT and adjuvant TMZ after RT. The study will evaluate escalating doses of LC delivered by IV infusion weekly as a gravity infusion (without infusion pump). Within each cohort, the dose will remain the same. In the first cohort, dosing will begin at Level 1 (300 mg/m2). The infusion of LC will begin at the start of CRT. Patients will be evaluable for the cohort if they have completed 80% of the planned doses of LC, 80% of RT and 60% of TMZ within the first 10 weeks of treatment. Patients who experience a dose-limiting toxicity (DLT) will be evaluable for the cohort if they have received at least 1 dose of LC.

Radiotherapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Radiation therapy for:

• Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma

Approved in United States as Radiation therapy for:

• Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma

Approved in Canada as Radiation therapy for:

• Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma

Approved in Japan as Radiation therapy for:

• Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma

Approved in China as Radiation therapy for:

• Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma

Approved in Switzerland as Radiation therapy for:

• Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma

Who Is Running the Clinical Trial?

SignPath Pharma, Inc.

Lead Sponsor

Trials

3

Recruited

110+

Avance Clinical

Collaborator

Trials

4

Recruited

200+

Avance Clinical Pty Ltd.

Industry Sponsor

Trials

23

Recruited

3,700+

Findings from Research

Temozolomide (TMZ) is the only anticancer drug proven to improve survival in glioblastoma when used with radiotherapy, showing high concentrations in brain tumors and cerebrospinal fluid, which enhances its effectiveness.

Molecular markers like MGMT promoter methylation can predict better responses to TMZ treatment, but side effects such as myelosuppression and nausea are common, necessitating precautions like prophylaxis against Pneumocystis carinii pneumonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Temozolomide: Temodal]. Shinoura, N., Yamada, R., Tabei, Y., et al.[2018]

In a study of 27 patients with newly diagnosed high-grade gliomas, the combination of temozolomide (TMZ) and radiation therapy (RT) demonstrated promising efficacy, with a median overall survival of 19 months and a one-year survival rate of 81.2%.

The treatment was well tolerated with no drug toxicity-related mortality, indicating a favorable safety profile, especially in patients under 50 years old and those who had debulking surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The outcomes of concomitant radiation plus temozolomide followed by adjuvant temozolomide for newly diagnosed high grade gliomas: the preliminary results of single center prospective study. Shawky, H., Abo Hamar, AH., Galal, S., et al.[2020]

In a randomized trial involving 144 patients with anaplastic astrocytoma (AA) and glioblastoma (GBM), neoadjuvant temozolomide (NeoTMZ) did not show a survival advantage for the overall population or for GBM patients compared to radiotherapy alone.

However, patients with AA who received NeoTMZ had a significantly longer median survival of 95.1 months compared to 35.2 months for those receiving only radiotherapy, indicating a potential benefit of NeoTMZ specifically for AA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative neoadjuvant temozolomide before radiotherapy versus standard radiotherapy in patients 60 years or younger with anaplastic astrocytoma or glioblastoma: a randomized trial. Malmström, A., Poulsen, HS., Grønberg, BH., et al.[2018]

Temozolomide (TMZ) significantly enhances the effectiveness of gamma irradiation in treating glioma cells, demonstrating a notable increase in radiosensitivity compared to irradiation alone, based on in vitro studies with U87MG cell lines.

The study involved various treatment groups over 24, 48, and 72 hours, and the combination of TMZ and irradiation resulted in significantly lower cell viability, indicating a more effective treatment strategy for gliomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In Vitro Radiosensitizing Effects of Temozolomide on U87MG Cell Lines of Human Glioblastoma Multiforme. Borhani, S., Mozdarani, H., Babalui, S., et al.[2020]

This meta-analysis aims to evaluate the effectiveness and safety of combining temozolomide (TMZ) with whole brain radiotherapy (WBRT) in patients with brain metastases from non-small cell lung cancer (NSCLC), focusing on outcomes like overall survival and quality of life.

The study will systematically review randomized controlled trials to determine if the addition of TMZ improves clinical outcomes compared to WBRT alone, potentially offering new insights into treatment strategies for advanced NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide plus whole brain radiotherapy for the treatment of non-small-cell lung cancer patients with brain metastases: A protocol of an updated systematic review and meta-analysis. Duan, H., Zheng, SY., Zhou, T., et al.[2022]

Temozolomide (TMZ) is an effective oral treatment for malignant gliomas, providing significant survival benefits while being generally well tolerated by patients.

While most side effects of TMZ are mild to moderate, there is a risk of severe hematologic adverse events, such as myelodysplastic syndrome and aplastic anemia, which have been documented in the literature.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide-related hematologic toxicity. Scaringi, C., De Sanctis, V., Minniti, G., et al.[2018]

Temozolomide (TMZ) is commonly used as an adjuvant therapy for malignant glioma, but in this case study, a patient developed treatment-related acute myeloid leukemia (t-AML) after receiving 15 cycles of TMZ, highlighting a rare but serious complication.

The case raises questions about the duration of TMZ therapy, as the patient showed no tumor progression but still developed t-AML, suggesting a need for better guidelines to balance treatment benefits and risks in long-term TMZ use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Case of Therapy-Related Acute Myeloid Leukemia Associated with Adjuvant Temozolomide Chemotherapy for Anaplastic Astrocytoma. Kosugi, K., Saito, K., Takahashi, W., et al.[2018]

Temozolomide (TMZ) can cause severe drug-induced toxic hepatitis, as demonstrated in a case where a patient developed significant liver issues after 5 weeks of treatment for glioblastoma, highlighting the importance of monitoring liver function during therapy.

To prevent serious complications, including potentially life-threatening conditions, it is crucial to monitor liver enzyme levels twice weekly during TMZ treatment and to discontinue the drug immediately if hepatitis is suspected.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide-induced liver damage. A case report. Becker, F., Hecht, M., Schmidtner, J., et al.[2021]

Temozolomide (TMZ) is generally safe with mild to moderate side effects, but this case report highlights a rare instance of severe aplastic anemia (AA) in a 68-year-old female patient following treatment for glioblastoma, indicating a potential serious risk associated with the drug.

The patient's AA was managed successfully with supportive care, including platelet transfusions and growth factor treatment, and her blood counts returned to normal within 38 days, emphasizing the importance of monitoring blood parameters during and after TMZ treatment to detect such rare toxicities early.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide-induced aplastic anaemia: Case report and review of the literature. Gilbar, PJ., Pokharel, K., Mangos, HM.[2022]

In a phase II trial involving 19 patients, the combination of temozolomide (TMZ) and pegylated liposomal doxorubicin showed an overall response rate of 36.8%, with three patients achieving a complete response and four a partial response, indicating promising efficacy in treating brain metastases from solid tumors.

The treatment was well tolerated, with manageable toxicities, and resulted in a median overall survival of 10.0 months and a median progression-free survival of 5.5 months, along with significant improvements in quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of temozolomide plus pegylated liposomal doxorubicin in the treatment of brain metastases from solid tumours. Caraglia, M., Addeo, R., Costanzo, R., et al.[2018]

Concurrent treatment with temozolomide (TMZ) and radiation therapy (RT) significantly improves survival in patients with glioblastoma multiforme (GBM), particularly in tumors with O6-methylguanine-DNA methyltransferase (MGMT) methylation, showing a median survival ratio of 5.7 compared to 2.3 for unmethylated tumors.

The study found that only a subset of MGMT methylated tumors benefits from the combined therapy, while sequential treatment of RT followed by TMZ is less effective than concurrent administration, highlighting the importance of treatment timing and tumor characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiosensitizing effects of temozolomide observed in vivo only in a subset of O6-methylguanine-DNA methyltransferase methylated glioblastoma multiforme xenografts. Carlson, BL., Grogan, PT., Mladek, AC., et al.[2022]

References

1. Japan pubmed.ncbi.nlm.nih.gov

[Temozolomide: Temodal]. [2018]

2. England pubmed.ncbi.nlm.nih.gov

The outcomes of concomitant radiation plus temozolomide followed by adjuvant temozolomide for newly diagnosed high grade gliomas: the preliminary results of single center prospective study. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Postoperative neoadjuvant temozolomide before radiotherapy versus standard radiotherapy in patients 60 years or younger with anaplastic astrocytoma or glioblastoma: a randomized trial. [2018]

4. Iran pubmed.ncbi.nlm.nih.gov

In Vitro Radiosensitizing Effects of Temozolomide on U87MG Cell Lines of Human Glioblastoma Multiforme. [2020]

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

Temozolomide plus whole brain radiotherapy for the treatment of non-small-cell lung cancer patients with brain metastases: A protocol of an updated systematic review and meta-analysis. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Temozolomide-related hematologic toxicity. [2018]

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

A Case of Therapy-Related Acute Myeloid Leukemia Associated with Adjuvant Temozolomide Chemotherapy for Anaplastic Astrocytoma. [2018]

8. Germany pubmed.ncbi.nlm.nih.gov

Temozolomide-induced liver damage. A case report. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Temozolomide-induced aplastic anaemia: Case report and review of the literature. [2022]

10. Germany pubmed.ncbi.nlm.nih.gov

Phase II study of temozolomide plus pegylated liposomal doxorubicin in the treatment of brain metastases from solid tumours. [2018]

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

Radiosensitizing effects of temozolomide observed in vivo only in a subset of O6-methylguanine-DNA methyltransferase methylated glioblastoma multiforme xenografts. [2022]