Tolinapant + Radiation for Head and Neck Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Nicole C Schmitt, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Waitlist Available

Sponsor: Emory University

Must not be taking: Antipsychotics, Antiarrhythmics, Antidepressants, others

Disqualifiers: Prior radiotherapy, Cardiovascular disease, HIV, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests a new drug, tolinapant, combined with radiation therapy for head and neck cancer patients who can't use the standard treatment. Tolinapant may block enzymes that help cancer grow, while radiation kills cancer cells.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does exclude certain medications known to cause QT prolongation (a heart rhythm condition). It's best to discuss your current medications with the trial team to see if any adjustments are needed.

What data supports the effectiveness of the treatment Tolinapant + Radiation for Head and Neck Cancer?

The use of advanced radiation techniques like Intensity Modulated Radiation Therapy (IMRT) and Image Guided Radiation Therapy (IGRT) in head and neck cancer has been shown to improve tumor targeting while reducing damage to normal tissues, leading to better outcomes with fewer side effects. Additionally, combining radiation with systemic therapies, such as platinum-based chemotherapy, is a standard approach that has proven benefits in treating head and neck cancer. ^{1 2 3 4 5}

Is the combination of Tolinapant and radiation therapy safe for humans?

Radiation therapy can cause nausea and vomiting in many patients, but these side effects can often be managed with antiemetic drugs (medications that prevent nausea and vomiting). The safety of Tolinapant specifically in combination with radiation therapy is not detailed in the provided research, so further information from clinical trials would be needed to assess its safety. ^{6 7 8 9 10}

What makes the Tolinapant + Radiation treatment unique for head and neck cancer?

The Tolinapant + Radiation treatment is unique because it combines a novel drug, Tolinapant, with advanced radiation techniques like Intensity-Modulated Radiation Therapy (IMRT) and Image-Guided Radiation Therapy (IGRT), which allow for precise targeting of tumors while sparing healthy tissue. This combination aims to improve tumor control and reduce side effects compared to conventional treatments. ^{4 11 12 13 14}

Research Team

Nicole C Schmitt, MD

Principal Investigator

Emory University

Eligibility Criteria

Adults with previously untreated, locally advanced head and neck cancer who cannot receive cisplatin. They must be in good physical condition (ECOG ≤1), have acceptable organ function, no severe hearing loss or neuropathy, and not be pregnant or breastfeeding. Participants need to use effective contraception and cannot have a history of significant mental illness or substance abuse.

Inclusion Criteria

I have a confirmed diagnosis of head and neck cancer that hasn't been treated yet, and I can't receive cisplatin with my radiation.

I cannot receive cisplatin due to my age or other health conditions.

I am 18 years old or older.

Exclusion Criteria

Receiving any other investigational agents or device within 21 days before study drugs

History of allergic reactions to compounds similar to tolinapant

I have had radiation therapy to my head or neck.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tolinapant orally and undergo radiation therapy for a total of 35 fractions over 7 weeks

7 weeks

Weekly visits for radiation therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Follow-up visits at 1, 3, 6, 12, and 24 months

Treatment Details

Interventions

• Radiation Therapy (Radiation)
• Tolinapant (Inhibitor of Apoptosis Protein (IAP) Antagonist)

Trial Overview The trial is testing the combination of a new drug called Tolinapant with radiation therapy against head and neck cancers that can't be treated with cisplatin. The goal is to see if this combo is safe and more effective at killing cancer cells than standard treatments.

Participant Groups

Group I: Treatment (tolinapant, radiation therapy) Experimental Treatment 2 Interventions

Patients undergo standard of care radiation therapy for a total of 35 fractions over 7 weeks and receive tolinapant PO daily for 7 days during weeks 1, 3, 5, and 7 of radiation therapy in the absence of disease progression or unacceptable toxicity.

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

🇪🇺 Approved in European Union as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

🇺🇸 Approved in United States as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

🇨🇦 Approved in Canada as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

🇯🇵 Approved in Japan as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

🇨🇳 Approved in China as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

🇨🇭 Approved in Switzerland as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Emory University/Winship Cancer Institute Atlanta, GA

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1735

Patients Recruited

2,605,000+

National Cancer Institute (NCI)

Collaborator

Trials

14080

Patients Recruited

41,180,000+

Astex Pharmaceuticals, Inc.

Industry Sponsor

Trials

97

Patients Recruited

7,400+

Findings from Research

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concomitant chemoradiotherapy versus induction docetaxel, cisplatin and 5 fluorouracil (TPF) followed by concomitant chemoradiotherapy in locally advanced head and neck cancer: a phase II randomized study. Paccagnella, A., Ghi, MG., Loreggian, L., et al.[2020]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy and integrated treatment approaches in head and neck cancer. Vokes, EE.[2019]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The management of head and neck tumors with high technology radiation therapy. Mendez, LC., Moraes, FY., Poon, I., et al.[2016]

Intensity Modulated Radiation Therapy (IMRT) combined with Image Guided Radiation Therapy (IGRT) enhances treatment for head and neck cancer by improving tumor coverage while minimizing damage to normal tissues, leading to similar tumor control rates with less toxicity compared to conventional methods.

In the context of systemic therapy, platinum-based radiochemotherapy remains the standard treatment, and early evidence suggests that adding Cetuximab to cisplatin-based therapy does not provide additional benefits in primary treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current strategies in radiotherapy of head and neck cancer. Pütz, M., Wenz, F.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The chemotherapy of head and neck cancer. de Mulder, PH.[2019]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment implications for radiation-induced nausea and vomiting in specific patient groups. Horiot, JC., Aapro, M.[2007]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase III trial of postoperative radiochemotherapy +/- amifostine in head and neck cancer. Is there evidence for radioprotection? Vacha, P., Fehlauer, F., Mahlmann, B., et al.[2013]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation-induced nausea and vomiting in head and neck cancer: Is it something worth considering in the intensity modulated radiotherapy era? "A narrative review". Paiar, F., Cristaudo, A., Gonnelli, A., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolution of antiemetic studies for radiation-induced nausea and vomiting within an outpatient palliative radiotherapy clinic. McKenzie, E., Chan, D., Parsafar, S., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of granisetron and aprepitant in a patient who failed ondansetron in the prophylaxis of radiation induced nausea and vomiting: a case report. Rowbottom, L., Pasetka, M., McDonald, R., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Target coverage for head and neck cancers treated with IMRT: review of clinical experiences. Garden, AS., Morrison, WH., Rosenthal, DI., et al.[2018]

In a study of 98 nasopharynx cancer patients treated with a combination of helical tomotherapy (HT) and intensity-modulated proton therapy (IMPT), the combination therapy resulted in significantly lower rates of grade ≥2 mucositis compared to HT alone (45.7% vs 69.8%).

The combination therapy (HT/IMPT) showed comparable early oncologic outcomes with no significant differences in locoregional or distant failures, suggesting that it may provide a safer treatment option with reduced acute toxicity for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early clinical outcomes of helical tomotherapy/intensity-modulated proton therapy combination in nasopharynx cancer. Park, SG., Ahn, YC., Oh, D., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Setup margin for head-and-neck cancer patients receiving 2D-2D and 3D image-guided intensity-modulated radiation therapy]. Kovács, P., Szita, E., Schvarcz, K., et al.[2018]

Intensity Modulated Proton Therapy (IMPT) provided better target coverage for recurrent nasopharyngeal carcinoma (rNPC) compared to Intensity Modulated Radiotherapy (IMRT), achieving higher coverage percentages for both the gross tumor volume and clinical target volume.

While IMPT showed advantages in sparing critical neurological organs, it also resulted in higher maximum doses to the internal carotid artery and nasopharyngeal mucosa, indicating a need for careful monitoring of potential complications when using this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosimetric comparison of intensity modulated radiotherapy and intensity modulated proton therapy in the treatment of recurrent nasopharyngeal carcinoma. Hung, HM., Chan, OCM., Mak, CH., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Concomitant chemoradiotherapy versus induction docetaxel, cisplatin and 5 fluorouracil (TPF) followed by concomitant chemoradiotherapy in locally advanced head and neck cancer: a phase II randomized study. [2020]

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

Chemotherapy and integrated treatment approaches in head and neck cancer. [2019]

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

The management of head and neck tumors with high technology radiation therapy. [2016]

4. Germany pubmed.ncbi.nlm.nih.gov

Current strategies in radiotherapy of head and neck cancer. [2021]

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

The chemotherapy of head and neck cancer. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Treatment implications for radiation-induced nausea and vomiting in specific patient groups. [2007]

7. Germany pubmed.ncbi.nlm.nih.gov

Randomized phase III trial of postoperative radiochemotherapy +/- amifostine in head and neck cancer. Is there evidence for radioprotection? [2013]

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

Radiation-induced nausea and vomiting in head and neck cancer: Is it something worth considering in the intensity modulated radiotherapy era? "A narrative review". [2021]

9. Germany pubmed.ncbi.nlm.nih.gov

Evolution of antiemetic studies for radiation-induced nausea and vomiting within an outpatient palliative radiotherapy clinic. [2021]

10. China pubmed.ncbi.nlm.nih.gov

Efficacy of granisetron and aprepitant in a patient who failed ondansetron in the prophylaxis of radiation induced nausea and vomiting: a case report. [2022]

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

Target coverage for head and neck cancers treated with IMRT: review of clinical experiences. [2018]

12. England pubmed.ncbi.nlm.nih.gov

Early clinical outcomes of helical tomotherapy/intensity-modulated proton therapy combination in nasopharynx cancer. [2021]

13. Hungary pubmed.ncbi.nlm.nih.gov

[Setup margin for head-and-neck cancer patients receiving 2D-2D and 3D image-guided intensity-modulated radiation therapy]. [2018]

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

Dosimetric comparison of intensity modulated radiotherapy and intensity modulated proton therapy in the treatment of recurrent nasopharyngeal carcinoma. [2022]