Reduced Intensity Chemo for Oropharyngeal Cancer

Overseen By Kenneth S. Hu

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: NYU Langone Health

Disqualifiers: Diabetes, Pregnancy, AIDS, 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

Duration: 6-8 weeks

144 Participants Needed

Trial Summary

What is the purpose of this trial?

This will be a phase II single-arm clinical trial. The purpose of this study is to determine the feasibility of deescalating chemoradiation treatment based on mid-treatment tumor response determined by rapid nodal shrinkage and clearance of circulating HPV plasma tumor DNA . The primary objective of this study is to evaluate progression-free survival at 2 years.

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 oropharyngeal cancer?

Research shows that using cisplatin (a chemotherapy drug) with radiation therapy can be effective for treating advanced oropharyngeal cancer, and de-escalating (reducing) the dose and volume of treatment can lead to better functional outcomes for patients with HPV-positive oropharyngeal cancer. ^{1 2 3 4 5}

Is reduced intensity chemo for oropharyngeal cancer safe for humans?

Research shows that using cisplatin (a type of chemotherapy) with radiation is generally safe for treating head and neck cancers, including oropharyngeal cancer. Common side effects include blood-related issues and gastrointestinal problems, but serious kidney, ear, or nerve damage was not observed. Reduced-dose chemoradiation may also lower the risk of severe side effects compared to standard doses. ^{1 6 7 8 9}

How does the treatment of reduced intensity chemo with cisplatin and radiation differ from other treatments for oropharyngeal cancer?

This treatment uses a reduced intensity approach by combining cisplatin (a chemotherapy drug) with standard radiation, potentially offering a balance between effectiveness and reduced side effects compared to high-dose regimens. It aims to maintain efficacy while minimizing toxicity, which is particularly beneficial for patients with other health issues. ^{1 9 10 11 12}

Research Team

Kenneth S. Hu

Principal Investigator

NYU Langone Health

Eligibility Criteria

This trial is for adults with HPV-positive oropharyngeal cancer confirmed by p16 staining and detectable HPV DNA in the blood. They should have a specific stage of cancer (T1-T2, N1-N2b or T3, N1-N2b), no more than 10 pack-years of smoking history, good performance status, adequate organ function, and no prior allergic reaction to cisplatin. Pregnant women and those with certain health conditions like unstable heart disease or severe infections are excluded.

Inclusion Criteria

My cancer is a type of throat cancer called squamous cell carcinoma.

Detectable circulating plasma HPV DNA at baseline

Specific imaging requirements within 8 weeks of registration

Exclusion Criteria

Pregnancy

Exclusion Criteria for MRI including specific conditions

I have a neck cancer with an unknown starting point, even if it's p16 positive.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive standard radiation therapy and cisplatinum, with treatment de-escalation based on mid-treatment tumor response

6-8 weeks

Follow-up

Participants are monitored for safety, effectiveness, and late toxicity after treatment

2 years

Treatment Details

Interventions

• Cisplatinum
• Dose-Deescalated Treatment
• Standard Radiation Treatment

Trial Overview The study tests if lowering the dose of chemoradiation treatment based on how well tumors respond mid-treatment can be effective. It's a phase II trial focusing on patients' progression-free survival over two years using standard radiation combined with Cisplatinum chemotherapy.

Participant Groups

Group I: HPV-Positive Oropharyngeal Carcinoma (OPSCC) Experimental Treatment 3 Interventions

Standard radiation therapy + cisplatinum

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

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Lung cancer
• Bladder cancer
• Cervical cancer

Approved in United States as Platinol for:

• Metastatic testicular tumors
• Metastatic ovarian tumors
• Advanced bladder cancer

Approved in Canada as Cisplatin for:

• Metastatic testicular cancer
• Advanced ovarian cancer
• Bladder cancer

Approved in Japan as CDDP for:

• Testicular cancer
• Ovarian cancer
• Lung cancer
• Bladder cancer
• Cervical cancer

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

Findings from Research

Patients with locally advanced oropharyngeal squamous cell carcinoma who received cisplatin (CDDP) had a significantly better 2-year overall survival rate compared to those treated with cetuximab (CTX), with a hazard ratio of 1.68 indicating higher mortality for CTX users.

Cisplatin also resulted in lower overall treatment costs compared to CTX and carboplatin, despite higher rates of antiemetic use and hospital visits for side effects, suggesting it may be a more cost-effective option for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing outcomes of concurrent chemotherapy regimens in patients 65 years old or older with locally advanced oropharyngeal carcinoma. Amini, A., Eguchi, M., Jones, BL., et al.[2023]

In a study of 153 patients with advanced oropharyngeal and nasopharyngeal carcinoma, adding weekly cisplatin to radiotherapy significantly improved overall survival, with a median survival of 27 months for radiotherapy alone compared to not reached for the chemoradiotherapy group.

While chemoradiotherapy showed higher complete response rates (80.5% vs. 67.1%) and better overall survival, it also resulted in increased toxicity, with 40% of patients experiencing severe side effects compared to 16% in the radiotherapy group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concomitant chemoradiation versus radical radiotherapy in advanced squamous cell carcinoma of oropharynx and nasopharynx using weekly cisplatin: a phase II randomized trial. Sharma, A., Mohanti, BK., Thakar, A., et al.[2022]

In a Phase II clinical trial involving 63 patients with advanced oropharynx carcinoma, the addition of weekly Docetaxel during standard radiation therapy was found to be feasible, with good compliance to treatment protocols.

While the treatment resulted in significant acute toxic effects, such as 84% of patients experiencing Grade 3 and 4 mucositis, the overall survival rate at three years was 47%, indicating potential efficacy similar to other chemotherapy regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy with concomitant weekly docetaxel for Stages III/IV oropharynx carcinoma. Results of the 98-02 GORTEC Phase II trial. Calais, G., Bardet, E., Sire, C., et al.[2019]

Patients with HPV-positive oropharyngeal cancer who underwent risk- and response-adapted de-escalated radiation therapy (RT) and chemoradiation (CRT) showed significantly better functional outcomes, including improved swallowing function and higher body mass index (BMI), compared to those receiving standard high-dose treatment.

The study found that lower treatment intensity (RT50/CRT45) was associated with less PEG-tube dependency and reduced narcotic use, highlighting the benefits of de-escalation in treatment for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose and Volume De-Escalation for Human Papillomavirus-Positive Oropharyngeal Cancer is Associated with Favorable Posttreatment Functional Outcomes. Foster, CC., Seiwert, TY., MacCracken, E., et al.[2021]

In a study of 52 patients with advanced nodal disease (N2 to N3) from upper aerodigestive tract carcinoma, targeted chemoradiation using the RADPLAT protocol resulted in a 59% clinical complete response rate in evaluable heminecks.

The combination of targeted chemoradiation and planned selective neck dissection achieved a high regional disease control rate of 91%, indicating that this approach is effective in managing advanced neck disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of targeted chemoradiation and planned selective neck dissection to control bulky nodal disease in advanced head and neck cancer. Robbins, KT., Wong, FS., Kumar, P., et al.[2019]

In a study of 82 advanced head and neck cancer patients undergoing concurrent chemoradiotherapy with high-dose cisplatin, 26% experienced renal impairment, highlighting the need for careful monitoring of kidney function during treatment.

Risk factors for cisplatin-induced renal impairment included the use of calcium channel blockers and lower hemoglobin levels, while the use of proton pump inhibitors was associated with a reduced risk, suggesting potential strategies to enhance patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of Risk Factors for High-dose Cisplatin-induced Renal Impairment in Head and Neck Cancer Patients. Koide, H., Noda, S., Okunuki, Y., et al.[2022]

In a study involving 23 patients with HPV-positive oropharyngeal carcinoma, reduced dose chemoradiation (rdCRT) after induction chemotherapy showed similar progression-free survival (PFS) and overall survival (OS) rates compared to standard-dose chemoradiation (sdCRT), with 3-year PFS/OS rates of 83.3% for rdCRT and 87.5% for sdCRT.

The findings suggest that rdCRT could be a viable treatment option that reduces toxicity while maintaining effectiveness, supporting further Phase 3 clinical trials for radiation dose reduction in HPV-positive oropharyngeal carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Standard of care vs reduced-dose chemoradiation after induction chemotherapy in HPV+ oropharyngeal carcinoma patients: The Quarterback trial. Misiukiewicz, K., Gupta, V., Miles, BA., et al.[2020]

In a study of 35 patients with advanced squamous cell carcinoma of the head and neck, the combination of cis-platinum (CDDP) and radiotherapy (RT) resulted in a high complete response rate of 75%, with an overall response rate of 100%.

The treatment was well tolerated, with gastrointestinal and hematologic toxicities being the most common side effects, making CDDP plus RT a safe and effective option, especially for patients with good performance status and unresectable stage II or III disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simultaneous cis-platinum and radiotherapy in inoperable or locally advanced squamous cell carcinoma of the head and neck. Gasparini, G., Pozza, F., Recher, G., et al.[2018]

In a phase I-II study involving 12 patients with unresectable head and neck squamous cell carcinomas, the combination of radiation and cisplatin (CDDP) resulted in a complete response in 66% of patients, with some remaining disease-free for up to 34 months after treatment.

The recommended dose of CDDP was determined to be 6 mg/m2/day, with manageable side effects; notably, mucositis severity was similar to that of radiation alone, and there was no significant nephro-, oto-, or neurotoxicity observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy with concomitant continuous cisplatin infusion for unresectable tumors of the upper aerodigestive tract: results of a phase I study. Bachaud, JM., Chatelut, E., Canal, P., et al.[2019]

In a study of 83 patients with oropharyngeal, hypopharyngeal, or laryngeal cancer, treatment with weekly cisplatin during radiotherapy resulted in a 2-year local control rate of 84% and overall survival rate of 82%.

The 5-year survival estimates showed a local control rate of 79%, overall survival of 69%, and disease-specific survival of 76%, indicating that this treatment regimen is effective over the long term.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patterns of relapse following definitive treatment of head and neck squamous cell cancer by intensity modulated radiotherapy and weekly cisplatin. Loimu, V., Collan, J., Vaalavirta, L., et al.[2019]

In a study of 104 patients with locally advanced head and neck squamous cell carcinoma, there was no significant difference in overall survival or recurrence-free survival between those treated with high-dose cisplatin and those treated with weekly cisplatin after surgery and chemoradiation.

The results suggest that weekly cisplatin may be a preferable option for patients with HPV-positive oropharynx cancer, as it could help maintain survival rates while potentially reducing treatment-related toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant chemoradiation therapy with high-dose versus weekly cisplatin for resected, locally-advanced HPV/p16-positive and negative head and neck squamous cell carcinoma. Geiger, JL., Lazim, AF., Walsh, FJ., et al.[2022]

Patients with HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) and nonsmokers showed better overall and disease-free survival, regardless of whether they received high dose (HD) or low dose (LD) cisplatin, indicating the importance of tumor characteristics in treatment outcomes.

A cumulative cisplatin dose of ≥200 mg/m2 was linked to a lower rate of distant metastasis, with the HD regimen allowing more patients to reach this dose while maintaining a similar toxicity profile to the LD regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deployment of cisplatin in Veterans with oropharyngeal cancer: toxicity and impact on oncologic outcomes. Soliman, O., Wilde, DC., Kemnade, JO., et al.[2023]

References

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

Comparing outcomes of concurrent chemotherapy regimens in patients 65 years old or older with locally advanced oropharyngeal carcinoma. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Concomitant chemoradiation versus radical radiotherapy in advanced squamous cell carcinoma of oropharynx and nasopharynx using weekly cisplatin: a phase II randomized trial. [2022]

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

Radiotherapy with concomitant weekly docetaxel for Stages III/IV oropharynx carcinoma. Results of the 98-02 GORTEC Phase II trial. [2019]

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

Dose and Volume De-Escalation for Human Papillomavirus-Positive Oropharyngeal Cancer is Associated with Favorable Posttreatment Functional Outcomes. [2021]

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

Efficacy of targeted chemoradiation and planned selective neck dissection to control bulky nodal disease in advanced head and neck cancer. [2019]

6. Greece pubmed.ncbi.nlm.nih.gov

Analysis of Risk Factors for High-dose Cisplatin-induced Renal Impairment in Head and Neck Cancer Patients. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Standard of care vs reduced-dose chemoradiation after induction chemotherapy in HPV+ oropharyngeal carcinoma patients: The Quarterback trial. [2020]

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

Simultaneous cis-platinum and radiotherapy in inoperable or locally advanced squamous cell carcinoma of the head and neck. [2018]

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

Radiotherapy with concomitant continuous cisplatin infusion for unresectable tumors of the upper aerodigestive tract: results of a phase I study. [2019]

10. Ireland pubmed.ncbi.nlm.nih.gov

Patterns of relapse following definitive treatment of head and neck squamous cell cancer by intensity modulated radiotherapy and weekly cisplatin. [2019]

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

Adjuvant chemoradiation therapy with high-dose versus weekly cisplatin for resected, locally-advanced HPV/p16-positive and negative head and neck squamous cell carcinoma. [2022]

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

Deployment of cisplatin in Veterans with oropharyngeal cancer: toxicity and impact on oncologic outcomes. [2023]