Ketogenic Diet + Radiation & Chemotherapy for Glioblastoma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Jethro Hu

Must not be taking: Experimental therapy

Disqualifiers: Vegan, Vegetarian, Lipid metabolism disorders, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

21 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Enrolled subjects will be placed on a 16-week ketogenic diet (subject specific as prescribed by RD) while receiving standard of care cancer treatment (Radiation + Temozolomide). Study dietitians will create personalized meal plans for each patient with the goal of achieving and maintaining protocol defined metabolic ketosis. Subjects will be monitored for safety, nutrition, quality of life, and standard of care tumor assessments over the course of the study.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, patients on low and managed doses of steroids are allowed, and those on high doses are excluded. It's best to discuss your specific medications with the trial team.

Is the combination of a ketogenic diet, radiation, and temozolomide safe for treating glioblastoma?

Temozolomide, when used with radiation, is generally considered safe but can cause blood-related side effects like myelosuppression (reduced bone marrow activity) and, rarely, more severe conditions like aplastic anemia. These side effects are uncommon, but they can lead to treatment delays or discontinuation. ^{1 2 3 4 5}

What makes the ketogenic diet combined with radiation and chemotherapy unique for treating glioblastoma?

This treatment is unique because it combines a ketogenic diet, which lowers blood sugar and increases ketones, with standard radiation and chemotherapy. The ketogenic diet may help improve outcomes by targeting the energy metabolism of brain tumors, potentially enhancing the effectiveness of traditional treatments. ^{6 7 8 9 10}

What data supports the effectiveness of the drug Temozolomide when used with radiation for treating glioblastoma?

Research shows that Temozolomide, when used with radiation, improves survival in glioblastoma patients. In one study, the two-year survival rate was 26.5% with Temozolomide and radiation, compared to 10.4% with radiation alone. ^{4 11 12 13 14}

Who Is on the Research Team?

Jethro Hu, MD

Principal Investigator

Cedars-Sinai Medical Center Samuel Oschin Comprehensive Cancer Institute

Are You a Good Fit for This Trial?

Adults over 18 with newly diagnosed glioblastoma can join this trial if they're being treated at Cedars-Sinai Medical Center or elsewhere for chemotherapy/radiation. They must be able to follow a ketogenic diet, have a BMI of ≥22, and be on low doses of steroids. Excluded are those with certain medical conditions, high steroid doses, vegan/vegetarian diets, allergies to specific materials used in the study tools, and incompatible implants.

Inclusion Criteria

I have been diagnosed with glioblastoma recently and have not started post-radiation chemotherapy.

I am taking a low dose of steroids, no more than 8 mg of dexamethasone or its equivalent.

I am being treated for glioblastoma at Cedars-Sinai Medical Center.

Exclusion Criteria

Patients whose most recent renal function test does not meet Cedars-Sinai Medical center standard of care MRI contrast protocol requirements (glomerular filtration rate <45ml/min).

Inability to adhere to the protocol

Patients with history of allergic reactions to surgical steel or elastomer/rubber are excluded from the activity monitor portion of the study. Because the activity monitor uses a Bluetooth low energy Transceiver, individuals using pacemakers, implantable cardiac defibrillators, neuro-stimulation devices, cochlear implants, hearing aids, or other electronic medical equipment should also be excluded from wearing the activity monitor. They can still use the Aria scale to record weight.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a 16-week ketogenic diet in combination with standard-of-care radiation and temozolomide

16 weeks

Regular visits for monitoring and diet adjustment

Follow-up

Participants are monitored for safety, nutrition, quality of life, and tumor assessments after treatment

4 weeks

Long-term follow-up

Participants are monitored for overall survival and time-to-progression

60 months

What Are the Treatments Tested in This Trial?

Interventions

• Ketogenic Diet
• Standard-of-care radiation
• Temozolomide

Trial Overview The trial tests how well patients with glioblastoma respond to a personalized 16-week ketogenic diet while undergoing standard cancer treatments like radiation and Temozolomide. Dietitians will tailor meal plans aiming for metabolic ketosis. Patient safety, nutrition levels, life quality, and tumor response are monitored throughout.

How Is the Trial Designed?

Group I: Ketogenic diet+radiation+temozolomide Experimental Treatment 3 Interventions

Ketogenic diet in combination with standard-of-care radiation and standard-of-care temozolomide

Who Is Running the Clinical Trial?

Jethro Hu

Lead Sponsor

Trials

1

Recruited

20+

Published Research Related to This Trial

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]

Carmustine wafers (Gliadel) and temozolomide (Temodal) have been approved for treating glioblastoma, with temozolomide showing a median survival benefit of 2 months when used with radiotherapy, and a two-year survival rate of 26.5% compared to 10.4% with radiotherapy alone.

In patients who undergo complete tumor resection, the two-year survival rate can reach 38%, highlighting the potential effectiveness of these treatments in younger patients with good performance status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[What type of adjuvant chemotherapy should be proposed for the initial treatment of glioblastoma?]. Ducray, F., Honnorat, J.[2018]

Temozolomide is primarily used for treating refractory central nervous system cancers like anaplastic astrocytoma and glioblastoma, but ongoing clinical trials are exploring its efficacy and safety in newly diagnosed gliomas and other types of tumors.

Research is also investigating different dosing schedules and combinations with other treatments, suggesting that temozolomide could be a versatile option in cancer therapy beyond its current approved uses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future directions for temozolomide therapy. Yung, WK.[2019]

In a study of 128 patients with high-grade gliomas, the combination of radiotherapy and temozolomide showed favorable outcomes, with only 9% experiencing grade 3 hematological toxicity and no grade 4 toxicity reported, indicating a manageable safety profile.

Statistical analysis revealed that factors such as age, tumor histology, and the use of temozolomide were linked to improved 2-year overall survival, supporting the efficacy of this treatment regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide and radiotherapy as first-line treatment of high-grade gliomas. Corsa, P., Parisi, S., Raguso, A., et al.[2022]

In a study of 1157 glioblastoma multiforme patients, the addition of temozolomide (TMZ) to radiotherapy (RT) significantly improved median overall survival from 9.0 months with RT alone to 16.2 months with RT + TMZ (P < .001).

The two-year survival rate increased from 4% with RT alone to 25% with the combination of RT and TMZ, confirming the efficacy of TMZ in enhancing survival outcomes in GBM patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A population-based study on the effect of temozolomide in the treatment of glioblastoma multiforme. Rønning, PA., Helseth, E., Meling, TR., et al.[2022]

In a study of 87 newly diagnosed glioblastoma patients, only 5% experienced severe myelotoxicity during treatment with temozolomide (TMZ) and radiation therapy, indicating that while the risk exists, it is relatively low.

Factors such as female sex, low pretreatment platelet counts, and specific genetic markers were identified as potential predictors of severe myelotoxicity, suggesting that personalized treatment approaches could help mitigate risks in vulnerable patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and Genetic Factors Associated With Severe Hematological Toxicity in Glioblastoma Patients During Radiation Plus Temozolomide Treatment: A Prospective Study. Lombardi, G., Rumiato, E., Bertorelle, R., et al.[2018]

In a phase II clinical trial involving 21 patients with newly diagnosed glioblastoma multiforme (GBM), the combination of temozolomide (TMZ) with radiotherapy resulted in a one-year survival rate of 58% and a median survival time of 15.7 months, indicating its efficacy in extending survival.

The treatment regimen was well-tolerated, with only mild to moderate non-hematological side effects and minimal severe hematological toxicity, suggesting that TMZ has a favorable safety profile compared to traditional chemotherapy agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide in radio-chemotherapy combined treatment for newly-diagnosed glioblastoma multiforme: phase II clinical trial. Lanzetta, G., Campanella, C., Rozzi, A., et al.[2018]

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]

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]

A retrospective study of 53 glioblastoma multiforme patients indicated that a ketogenic diet (KD) is safe and well tolerated during standard treatment, with no severe toxicities reported and only mild fatigue experienced.

Patients on a KD had significantly lower serum glucose levels (mean 84 mg/dl) compared to those on a standard diet (mean 122 mg/dl), suggesting that dietary carbohydrate restriction may positively influence treatment response and prognosis in GBM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting metabolism with a ketogenic diet during the treatment of glioblastoma multiforme. Champ, CE., Palmer, JD., Volek, JS., et al.[2022]

A ketogenic diet (KD) combined with standard treatments for aggressive primary brain tumors (APBT) showed promising results, with three younger patients surviving significantly longer (52-74 months) compared to older patients, who had an average survival of 8 months after diagnosis.

The study demonstrated that it is feasible to maintain dietary-induced ketosis in patients with APBT, suggesting that further research is needed to explore the potential benefits of KD, particularly in younger patients under 40.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long Term Survivals in Aggressive Primary Brain Malignancies Treated With an Adjuvant Ketogenic Diet. Schwartz, KA., Noel, M., Nikolai, M., et al.[2023]

The ketogenic diet (KD) has been shown to be an effective therapy for patients with malignant gliomas, with a mean overall survival of 15.9 months reported across nine studies.

While the KD may improve survival rates, its impact on quality of life remains inconclusive, with only 44.4% of studies reporting improvements in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of the Ketogenic Diet in the Treatment of Gliomas: A Systematic Review. Sargaço, B., Oliveira, PA., Antunes, ML., et al.[2022]

Preclinical studies indicate that ketogenic or caloric restricted diets (KCRDs) can reduce tumor growth in malignant gliomas, particularly when blood glucose levels are decreased, although improved survival was only observed in a minority of cases.

Preliminary clinical data suggest that KCRDs are safe and feasible for glioma patients, but there is not enough evidence yet to confirm their effectiveness in improving survival or quality of life, highlighting the need for further prospective studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of malignant gliomas with ketogenic or caloric restricted diets: A systematic review of preclinical and early clinical studies. Noorlag, L., De Vos, FY., Kok, A., et al.[2022]

Citations

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

[Temozolomide: Temodal]. [2018]

2. France pubmed.ncbi.nlm.nih.gov

[What type of adjuvant chemotherapy should be proposed for the initial treatment of glioblastoma?]. [2018]

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

Future directions for temozolomide therapy. [2019]

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

Temozolomide and radiotherapy as first-line treatment of high-grade gliomas. [2022]

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

A population-based study on the effect of temozolomide in the treatment of glioblastoma multiforme. [2022]

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

Clinical and Genetic Factors Associated With Severe Hematological Toxicity in Glioblastoma Patients During Radiation Plus Temozolomide Treatment: A Prospective Study. [2018]

7. Greece pubmed.ncbi.nlm.nih.gov

Temozolomide in radio-chemotherapy combined treatment for newly-diagnosed glioblastoma multiforme: phase II clinical trial. [2018]

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

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

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

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

10. England pubmed.ncbi.nlm.nih.gov

Metabolic management of glioblastoma multiforme using standard therapy together with a restricted ketogenic diet: Case Report. [2023]

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

Targeting metabolism with a ketogenic diet during the treatment of glioblastoma multiforme. [2022]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Long Term Survivals in Aggressive Primary Brain Malignancies Treated With an Adjuvant Ketogenic Diet. [2023]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Effects of the Ketogenic Diet in the Treatment of Gliomas: A Systematic Review. [2022]

14. England pubmed.ncbi.nlm.nih.gov

Treatment of malignant gliomas with ketogenic or caloric restricted diets: A systematic review of preclinical and early clinical studies. [2022]