Reduced Radiation + Chemotherapy for Oral Squamous Cell Carcinoma

Not currently recruiting at 12 trial locations

Overseen By Nancy Lee, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Prior head/neck radiation, Simultaneous cancers, Recent myocardial infarction, 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: 1

Duration: 5-10 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a lower dose of radiation, combined with standard chemotherapy, matches the effectiveness of the current heavier treatment for a specific type of HPV-linked throat cancer. The focus is on oropharyngeal squamous cell carcinoma, especially in patients whose cancer is not aggravated by low oxygen levels in the tumor (hypoxia). Participants may qualify if they have been diagnosed with HPV-related throat cancer and have not previously received radiation for it. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that a lower radiation dose of 30 Gy over 3 weeks can reduce side effects for patients with oropharyngeal cancer. One study found that this reduced dose, when combined with chemotherapy, was well tolerated. Most patients avoided severe side effects while still receiving effective treatment.

For chemotherapy drugs like 5-Fluorouracil, about 30% of patients might experience side effects due to genetic differences, including nausea or low blood counts. Carboplatin, another chemotherapy drug, is generally well tolerated. Studies have shown it is safe when used with radiation therapy, effectively treating cancer with manageable side effects. Cisplatin, often used in cancer treatments, can cause mouth sores, nausea, and low white blood cells, but these side effects are usually temporary and manageable.

Proton therapy, a type of radiation treatment, causes fewer side effects compared to traditional radiation methods, allowing patients to feel better during and after treatment.

Overall, studies support these treatments as safe and effective for many people. However, side effects can vary from person to person. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it explores a reduced radiation approach combined with chemotherapy for treating oral squamous cell carcinoma, specifically targeting HPV-associated oropharyngeal carcinoma. Unlike the standard of care, which often involves higher doses of radiation over a longer period, this trial uses a lower dose of 30 Gy over just 3 weeks. This could potentially lead to fewer side effects and a better quality of life for patients. Additionally, the use of proton therapy is noteworthy, as it offers a more precise delivery of radiation, sparing healthy tissues and potentially reducing complications. This trial aims to determine if these modifications can effectively treat the cancer with less harm to the patient.

What evidence suggests that this trial's treatments could be effective for oral squamous cell carcinoma?

Research has shown that reducing radiation to 30 Gy over three weeks can still effectively treat HPV-positive throat cancer. In this trial, participants in different arms will receive various treatments. Some will receive this reduced-dose radiation along with chemotherapy, which studies have found can control the disease and might improve quality of life. The drug 5-Fluorouracil, often used with other treatments, has proven effective for head and neck cancers, including this type of throat cancer. Participants may also receive chemotherapy drugs like Carboplatin or Cisplatin; both work similarly well for HPV-positive throat cancers, but Cisplatin is often preferred due to its strong track record. Proton therapy, another treatment option in this trial, is a precise type of radiation treatment that has been effective for HPV-positive cancers and causes fewer side effects than traditional radiation. Overall, these treatments offer promising options for managing HPV-positive throat cancer. ^{2 3 6 7 8}

Who Is on the Research Team?

Nancy Lee, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

Adults with HPV-associated oropharyngeal squamous cell carcinoma, stages T1-2 N1-2c, can join this trial. They must have good blood counts, kidney and liver function, and no history of chemotherapy for the cancer being studied. Pregnant women must test negative. Those with prior head/neck radiation or other cancers (except certain skin cancers) within 3 years are excluded.

Inclusion Criteria

My kidney function is good, based on recent tests.

Bilirubin ≤ 2 mg/dl

AST or ALT ≤ 3 x the upper limit of normal

Exclusion Criteria

I might have other primary cancers, but the lead researcher agrees I can join.

I've been cancer-free for 3 years, except for non-dangerous skin cancers.

I have not undergone particle therapy like proton therapy for my condition in Cohort A.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Imaging

Participants undergo BF-FMISO PET/CT imaging to determine hypoxia status

1 week

1 visit (in-person)

Treatment

Participants receive 30Gy radiation therapy concurrent with 2 cycles of chemotherapy

5-10 weeks

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• 30 Gy over 3 weeks
• 5Fluorouracil
• Carboplatin
• Cisplatin
• Proton Therapy

Trial Overview The study tests if a reduced radiation dose (30 Gy over 3 weeks) combined with standard chemotherapy is as effective as the current treatment for specific throat cancer patients without oxygen-deficient tumors. Cohort B allows optional surgery and proton therapy.

How Is the Trial Designed?

Group I: Arm B: HPV associated oropharyngeal carcinoma Experimental Treatment 6 Interventions

HPV associated oropharyngeal carcinoma subjects who also have no evidence of hypoxia.

Group II: Arm A: HPV associated oropharyngeal carcinoma Experimental Treatment 5 Interventions

HPV associated oropharyngeal carcinoma subjects who also have no evidence of hypoxia. This arm is closed to accrual.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

The TPF regimen, which includes docetaxel, cisplatin, and 5-fluorouracil, showed a 74% overall response rate and a 24% complete response rate in 46 patients with unresectable stage IV head and neck carcinomas, indicating its efficacy compared to the standard PF regimen.

However, the TPF regimen was associated with significant treatment-related toxicities, including myelosuppression in 78% of patients, suggesting that while it may be more effective, it also carries a higher risk of severe side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II Study of Docetaxel, Cisplatin and 5- Fluorouracil (TPF) In Patients with Locally Advanced Head and Neck Carcinomas. Ansari, M., Omidvari, S., Mosalaei, A., et al.[2021]

In a phase II trial involving 32 patients with recurrent or metastatic head and neck squamous cell carcinoma, the combination of carboplatin and raltitrexed demonstrated moderate efficacy, with a 22% partial response rate and a median survival duration of 9.8 months.

The treatment was generally safe, with manageable toxicity; however, 25% of patients experienced severe neutropenia, and one patient dropped out due to persistent hepatic toxicity, indicating the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin in combination with raltitrexed in recurrent and metastatic head and neck squamous cell carcinoma: A multicentre phase II study of the Gruppo Oncologico Dell'Italia Meridionale (G.O.I.M.). Galetta, D., Giotta, F., Rosati, G., et al.[2014]

In a study involving 20 patients with advanced or relapsing upper aerodigestive tract carcinomas, a treatment regimen combining cisplatin and 5-fluorouracil with radiation resulted in a 75% objective response rate, including nine complete responses and six partial responses.

The treatment was associated with moderate toxicity, with rare occurrences of significant side effects like mucositis, leukopenia, and thrombocytopenia, suggesting that this combination therapy is both effective and relatively safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alteration of chemotherapy (cisplatin and 5-FU) and radiotherapy in the management of advanced or recurrent head and neck cancer: a phase II study. Grimaldi, A., Merlano, M., Benasso, M., et al.[2013]

In a phase II trial involving 55 patients with advanced head and neck carcinoma, the combination of Carboplatin and 5-FU resulted in a 33% complete response and a 54% partial response, indicating significant efficacy.

Carboplatin/5-FU demonstrated milder side effects compared to Cisplatin/5-FU, with tolerable myelotoxicity and no ototoxicity, leading to improved patient performance status and increased body weight.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Results of a phase II study with the new cytostatic drug carboplatin in combination with 5-fluorouracil in the primary treatment of advanced squamous cell cancers of the head and neck]. Volling, P., Schröder, M., Rauschning, W., et al.[2013]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8778604/

Evaluation of Substantial Reduction in Elective ... In this cohort study, reduced radiotherapy volume and dose of 30 Gy to the elective regions with concurrent chemotherapy in 276 patients with locally advanced ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03323463

NCT03323463 | Major De-escalation to 30 Gy for Select ... This non-randomized non-inferiority study will enroll HPV associated oropharyngeal carcinoma subjects. Subjects who also have no evidence of hypoxia will ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1879850018303163

Reducing the Radiation Therapy Dose Prescription for ... We have altered our radiation guidelines to allow substantial dose reduction to elective treatment regions and to omit radiation completely in other regions.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.20.03128

Reduced-Dose Radiation Therapy for HPV-Associated ... Reducing radiation treatment dose could improve the quality of life (QOL) of patients with good-risk human papillomavirus–associated oropharyngeal squamous ...

5. mskcc.org mskcc.org/clinical-updates/reducing-radiation-select-patients-hpv-associated-mouth-and-throat

Reducing Radiation for Select Patients with HPV- ... Based on the promising results with selecting hypoxia-negative patients to undergo a reduced dose to 30 Gy as noted in our pilot study above, we ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03323463

NCT03323463 | Major De-escalation to 30 Gy for Select ... The purpose of this study is to demonstrate that participants with HPV positive and hypoxia negative T1-2, N1-2c (AJCC, 7th ed.) oropharyngeal squamous cell ...

7. ecancer.org ecancer.org/en/journal/article/1901-outcomes-of-early-stage-oropharyngeal-squamous-cell-carcinoma-patients-treated-with-radical-radiation-a-single-institution-experience

Outcomes of early-stage oropharyngeal squamous cell ... The majority of the patients (80.4% (N = 90)) received a radiotherapy (RT) dose of 60 Gy in 26 fractions at 2.3 Gy per fraction over 5.5 weeks.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8168141/

Precision Radiotherapy: Reduction in Radiation for ... Patients with human papillomavirus–related oropharyngeal cancers have excellent outcomes but experience clinically significant toxicities ...