Reduced Radiation + Chemotherapy for Oral Squamous Cell Carcinoma

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

316 Participants Needed

Trial Summary

What is the purpose of this trial?

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 carcinoma receiving a major de-escalated radiation therapy with 2 cycles of standard chemotherapy is not inferior to comparable subjects treated with the current standard chemoradiation. Accrual for Cohort A has been completed. Cohort B is active and continues to enroll participants where surgery is optional and proton is allowed.

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.

What data supports the effectiveness of the treatment for oral squamous cell carcinoma?

Research shows that the combination of cisplatin and 5-fluorouracil (5-FU) is a standard and effective regimen for treating advanced head and neck cancers, including squamous cell carcinoma. Additionally, carboplatin, which is similar to cisplatin but with less severe side effects, has shown promising results when combined with 5-FU and radiation therapy, offering potential benefits for patients with head and neck cancers. ^{1 2 3 4 5}

Is the combination of reduced radiation and chemotherapy safe for treating oral squamous cell carcinoma?

Studies show that the combination of chemotherapy drugs like 5-Fluorouracil (5-FU) and cisplatin or carboplatin with radiation has been used in treating head and neck cancers. While these treatments can have side effects like nausea and blood cell changes, they are generally considered to have an acceptable safety profile. ^{1 2 4 6 7}

What makes this treatment for oral squamous cell carcinoma unique?

This treatment is unique because it combines reduced radiation with chemotherapy drugs like 5-Fluorouracil, Carboplatin, and Cisplatin, along with advanced Proton Therapy, which may offer a more targeted approach with potentially fewer side effects compared to traditional radiation methods. ^{1 2 4 7 8}

Research Team

Nancy Lee, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

References

1. Greece 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.). [2014]

2. India pubmed.ncbi.nlm.nih.gov

A prospective study to assess the efficacy and toxicity of 5-flurouracil and cisplatin versus taxane and cisplatin as induction chemotherapy in locally advanced head and neck squamous cell cancer in a regional cancer center in India. [2016]

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

Paclitaxel, 5-fluorouracil, hydroxyurea, and concomitant radiation therapy for poor-prognosis head and neck cancer. [2015]

4. Estonia 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. [2021]

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

Carboplatin in the treatment of squamous cell head and neck cancers. [2018]

6. Germany 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]. [2013]

7. Italy 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. [2013]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Concurrent chemoradiotherapy with low-dose cisplatin plus 5-fluorouracil for the treatment of patients with unresectable head and neck cancer. [2017]