Reduced Radiation + Chemotherapy for Throat Cancer

Recruiting at 7 trial locations

Overseen By Nancy Lee, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Prior head and neck radiation, 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: Unknown

121 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether lower doses of radiation can reduce side effects while remaining effective when combined with chemotherapy for HPV-positive throat cancer. It tests various chemotherapy drugs, such as cisplatin, carboplatin, and 5-fluorouracil (5-FU), alongside radiation. The trial targets individuals diagnosed with HPV-related throat cancer who have visible tumor sites. Participants are divided into groups to test these combinations. Those who have not undergone head and neck radiation and are free from other serious health issues may be suitable candidates. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to advancements in cancer treatment.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss your specific medications with the trial team to get a clear answer.

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

Research has shown that the treatments in this trial—carboplatin, cisplatin, 5-fluorouracil, and radiation—have been studied for safety in people. Carboplatin, when combined with radiation, is usually well-tolerated for head and neck cancers but can cause side effects like oral mucositis, which involves painful swelling and sores in the mouth.

Cisplatin, a common chemotherapy drug for many cancer types, can cause nausea and vomiting, though most side effects are mild to moderate. Its long history of use indicates a manageable safety profile.

5-fluorouracil, another widely tested chemotherapy drug, has proven effective in treating various cancers and is generally safe under medical supervision.

Radiation therapy is effective for throat cancer but can lead to side effects like changes in oral health and temporary discomfort. This study aims to determine if lowering radiation doses can reduce these side effects while still effectively treating the cancer.

Overall, these treatments have a history of safe use in people, though side effects can occur. Discussing potential risks and benefits with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the reduced radiation and chemotherapy protocol for throat cancer because it aims to minimize side effects while maintaining effectiveness. Standard treatments often involve high doses of radiation, which can lead to significant long-term damage. This new approach reduces radiation exposure and combines it with chemotherapy agents like Carboplatin and Paclitaxel, or its substitute Abraxane, tailored to the patient's specific cancer characteristics. The inclusion of advanced imaging techniques like 18F-FMISO PET scans allows for more precise targeting of cancer cells, potentially improving outcomes and quality of life for patients.

What evidence suggests that this trial's treatments could be effective for HPV-positive throat cancer?

Research has shown that using carboplatin and paclitaxel together may help treat head and neck cancers, including HPV-positive throat cancer. One study revealed that patients treated with nab-paclitaxel (a type of paclitaxel) and carboplatin had a 38% overall response rate, indicating many experienced tumor shrinkage. Another study found that 66.6% of patients with advanced oropharyngeal cancer survived for at least two years after treatment with similar chemotherapy drugs. In this trial, participants in different cohorts will receive various combinations of these treatments. For example, Cohort B will receive carboplatin and paclitaxel alongside radiation, while Cohort C may receive induction chemotherapy with carboplatin, paclitaxel, and possibly cetuximab. Combining carboplatin, paclitaxel, and cetuximab (a targeted therapy) has shown positive results, with a 65% overall response rate in some head and neck cancers. These findings suggest that these chemotherapy combinations could effectively manage HPV-positive throat cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Nancy Lee, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with HPV-positive throat cancer who have measurable disease, confirmed diagnosis, and adequate organ function. They must not have had prior head and neck radiation or chemotherapy for the current cancer, no other simultaneous primary cancers, and no severe active co-morbidities.

Inclusion Criteria

My throat cancer is caused by HPV.

Study-specific informed consent prior to study entry

I cannot tolerate certain chemotherapy drugs and will receive specific alternatives.

Exclusion Criteria

I have received chemotherapy for my current cancer.

Severe, active co-morbidity as defined

I have liver problems causing jaundice or blood clotting issues.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Chemotherapy

Participants receive induction chemotherapy of carboplatin, paclitaxel with or without cetuximab for 6 weeks

6 weeks

Radiation and Concurrent Chemotherapy

Participants receive reduced radiation therapy concurrent with chemotherapy drugs such as cisplatin, carboplatin, and 5-fluorouracil (5-FU), paclitaxel, or Abraxane

Duration not specified

Follow-up

Participants are monitored for locoregional control and recurrence for 2 years

2 years

What Are the Treatments Tested in This Trial?

Interventions

• 5-fluorouracil
• Carboplatin
• Cisplatin
• Radiation

Trial Overview The study tests if lower doses of radiation combined with standard chemotherapy (cisplatin, carboplatin, 5-fluorouracil) can reduce side effects in treating HPV-positive throat cancer. It includes imaging like PET/CT scans to assess treatment effectiveness.

How Is the Trial Designed?

Group I: Cohort D Experimental Treatment 5 Interventions

Participants diagnosed with hypoxia negative human papilloma virus (HPV) associated oropharyngeal carcinoma (OPC). Cohort D will just have T1- T2N0 participants. Paclitaxel can be substituted with Abraxane (Albumin-bound Paclitaxel). Will follow the guidelines for Cohort A and Cohort B for chemotherapy options.

Group II: Cohort C Experimental Treatment 5 Interventions

Participants diagnosed with hypoxia negative human papilloma virus (HPV) associated oropharyngeal carcinoma (OPC). For participants in Cohort C where induction chemotherapy is used, additional pre-treatment 18F-FMISO PET and post induction pre radiation FMISO PET Scans will be obtained. These patients will start with induction chemotherapy of carboplatin, paclitaxel with or without cetuximab for 6 weeks and follow the same precision chemoradiation algorithm as Cohort A. A window of +/- 2 days is acceptable during the induction phase Paclitaxel can be substituted with Abraxane (Albumin-bound Paclitaxel). For patients who cannot tolerate paclitaxel, Abraxane and the dose will be at 100mg/m\^2.

Group III: Cohort B Experimental Treatment 5 Interventions

Participants diagnosed with hypoxia negative human papilloma virus (HPV) associated oropharyngeal carcinoma (OPC). Participants in Cohort B will receive 1 cycle of carboplatin and Paclitaxol the same week of the start of radiation. Paclitaxel can be substituted with Abraxane (Albumin-bound Paclitaxel). Paclitaxel can be substituted with Abraxane and the dose will be 50mg/m\^2. For Cohort B, patients over 70yrs will be able to enroll regardless of Cisplatin or carboplatin/5-fluorouracil (FU) eligibility.

Group IV: Cohort A Experimental Treatment 5 Interventions

Participants diagnosed with hypoxia negative human papilloma virus (HPV) associated oropharyngeal carcinoma (OPC)

5-fluorouracil is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as 5-FU for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer
• Esophageal cancer
• Anal cancer

Approved in European Union as 5-FU for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer
• Esophageal cancer
• Anal cancer

Approved in Canada as 5-FU for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer
• Esophageal cancer
• Anal cancer

Approved in Japan as 5-FU for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer
• Esophageal cancer
• Anal cancer

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 combination of carboplatin (CBDCA) and tegafur (FT) resulted in a 62% overall response rate in patients with untreated squamous-cell carcinoma of the head and neck, indicating promising efficacy for this treatment regimen.

While the treatment was generally associated with moderate toxicity, it did lead to one treatment-related death, highlighting the need for careful monitoring of patients during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of carboplatin and tegafur (Ftorafur) as induction therapy in squamous-cell carcinoma of the head and neck. Gonzalez-Baron, M., Vicente, J., Martin, G., et al.[2019]

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]

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]

Docetaxel, when used in combination with platinum and 5-fluorouracil (5FU) as part of the TPF regimen, shows a high overall response rate of 85 to 90% in treating head and neck carcinoma, with manageable acute toxicity.

Docetaxel acts as a radiosensitizer, making it a feasible option for concurrent radiochemotherapy, but further trials are needed to determine the best combination regimen with radiation and other chemotherapy agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Docetaxel and squamous cell carcinoma of the head and neck]. Calais, G.[2018]

In a study of 143 patients with Stage III-IV head and neck squamous cell carcinoma, carboplatin-paclitaxel (CT) induction chemotherapy resulted in significantly better locoregional control (80.5%) and progression-free survival (73.2%) compared to docetaxel-cisplatin-5-fluorouracil (TPF) chemotherapy (55.5% and 60.7%, respectively).

TPF was associated with worse renal toxicity and a higher rate of chemotherapy dose reductions during treatment, suggesting that CT may be a safer and more effective option for patients undergoing induction chemotherapy before chemoradiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of carboplatin-paclitaxel to docetaxel-cisplatin-5-flurouracil induction chemotherapy followed by concurrent chemoradiation for locally advanced head and neck cancer. Herman, LC., Chen, L., Garnett, A., et al.[2021]

In a study of 51 patients with HPV-related oropharyngeal squamous cell carcinoma, one course of TPF chemotherapy resulted in a high partial response rate of 73%, indicating its potential effectiveness in predicting outcomes for subsequent chemoradiotherapy.

The study found that 85% of patients who underwent chemoradiotherapy achieved a complete response, with a 2-year survival rate of 92%, suggesting that TPF can help guide treatment decisions between chemoradiotherapy and surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predicting the efficacy of chemoradiotherapy for locally advanced human papilloma virus-related oropharyngeal squamous cell carcinoma using one course of TPF chemotherapy. Kondo, T., Tsukahara, K., Okamoto, I., et al.[2021]

Higher T and N stages in head and neck cancer are associated with lower rates of complete local control and survival, highlighting the need for improved treatment strategies.

Combined-modality treatments, such as induction chemotherapy followed by radiotherapy, show promise in enhancing survival and preserving organ function compared to aggressive surgery or radiotherapy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined modalities in the treatment of head and neck cancers. Aisner, J., Hiponia, D., Conley, B., et al.[2015]

In a study involving patients with resectable locally advanced head and neck cancer, chemotherapy with cis-platin and 5-fluorouracil (5-FU) after surgery was found to be feasible, with 78% of patients completing all three courses of treatment.

The chemotherapy regimen had acceptable toxicity levels, with the most common side effects being nausea and vomiting, while 62% of patients were alive after a minimum follow-up of 24 months, indicating potential effectiveness for further investigation in a Phase III trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy following surgery for head and neck cancer. A Radiation Therapy Oncology Group Study. Jacobs, JR., Pajak, TF., al-Sarraf, M., et al.[2019]

In a study of 160 patients with advanced oropharyngeal squamous cell carcinoma treated with carboplatin, paclitaxel, and radiation over 10 years, the overall survival rates were 81.7% at 3 years and 70.7% at 5 years, indicating effective treatment outcomes.

The treatment demonstrated an acceptable side effect profile, with the most common adverse effect being acute dysphagia (75.25%), and only 11.9% of patients experiencing significant hematologic toxicities, suggesting carboplatin may be a safer alternative to cisplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival outcomes in patients with oropharyngeal cancer treated with carboplatin/paclitaxel and concurrent radiotherapy. Roskies, M., Kay-Rivest, E., Mascarella, MA., et al.[2018]

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

Carboplatin was associated with fewer severe side effects compared to cisplatin, making it a safer alternative for induction chemotherapy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin. The better platinum in head and neck cancer? Volling, P., Schröder, M., Rauschning, W., et al.[2019]

In a randomized trial involving 95 patients with stage IV-M0 head and neck cancer, the combination of cisplatin (CDDP) and fluorouracil (FU) was found to be more effective than carboplatin (CBDCA) and FU, with significantly better response rates and survival outcomes.

While CDDP-FU showed better efficacy, it was associated with higher rates of mucositis and vomiting, whereas CBDCA-FU led to more hematologic toxicity, indicating a trade-off in side effects between the two treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized trial of neoadjuvant cisplatin and fluorouracil versus carboplatin and fluorouracil in patients with stage IV-M0 head and neck cancer. De Andrés, L., Brunet, J., López-Pousa, A., et al.[2017]

Citations

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5-Fluorouracil and cisplatin in the treatment of advanced ... The median survival of the responders was 15 months (95% CI 11.3–18.7 months), and of the non-responders 9 months (95% CI 5.6–12.4 months) (P=0.0067).

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