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

Trial Summary

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.

What data supports the effectiveness of the drug combination of reduced radiation, 5-fluorouracil, and platinum-based chemotherapy for throat cancer?

Research shows that combining chemotherapy drugs like cisplatin and 5-fluorouracil with radiation can improve survival rates in advanced head and neck cancers compared to radiation alone. Carboplatin, a similar drug to cisplatin, is noted for having less toxicity, making it a potentially effective alternative in combination treatments. ^{1 2 3 4 5}

Is the combination of reduced radiation and chemotherapy safe for throat cancer treatment?

The combination of carboplatin and 5-fluorouracil (5-FU) is generally considered to have a more favorable safety profile compared to cisplatin and 5-FU, with less severe side effects like nausea, vomiting, and kidney issues. While some side effects like low blood cell counts and mild kidney problems can occur, they are usually manageable and reversible. ^{1 6 7 8 9}

How is the reduced radiation and chemotherapy treatment for throat cancer different from other treatments?

This treatment combines reduced radiation with chemotherapy drugs like 5-fluorouracil, carboplatin, and cisplatin, aiming to lower toxicity while maintaining effectiveness. Carboplatin is used instead of cisplatin in some cases due to its less severe side effects, and the combination with radiation is designed to enhance the treatment's cancer-fighting ability. ^{1 5 10 11 12}

What is the purpose of this trial?

The purpose of this study is to find out if lower doses of radiation may help reduce the side effects of radiation therapy in combination with standard-of-care chemotherapy in people with HPV-positive throat cancer. The chemotherapy drugs used in this study include cisplatin, carboplatin, and 5-fluorouracil (5- FU), paclitaxel and abraxane- (Albumin-bound Paclitaxel).

Research Team

Nancy Lee, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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]

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 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]

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 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 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]

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 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 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]

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. Germany 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. [2021]

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

Combined modalities in the treatment of head and neck cancers. [2015]

4. United States 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. [2017]

5. France pubmed.ncbi.nlm.nih.gov

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

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

Carboplatin. The better platinum in head and neck cancer? [2019]

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

Chemotherapy following surgery for head and neck cancer. A Radiation Therapy Oncology Group Study. [2019]

8. United States 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. [2019]

9. 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]

10. 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]

11. England pubmed.ncbi.nlm.nih.gov

Survival outcomes in patients with oropharyngeal cancer treated with carboplatin/paclitaxel and concurrent radiotherapy. [2018]

12. England 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. [2021]