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

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the possibility of safely reducing the intensity of chemoradiation (a combination of chemotherapy and radiation) for treating HPV-positive oropharyngeal cancer, which affects parts of the throat like the tonsils and the base of the tongue. Researchers aim to determine if this approach can maintain cancer control while potentially reducing side effects. Participants must have a specific type of throat cancer confirmed by tests, with evidence of the HPV virus in their blood and a low history of smoking. The main goal is to assess whether patients remain cancer-free for two years after treatment. As a Phase 2 trial, this research focuses on measuring 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?

Studies have shown that combining cisplatin with radiation therapy is generally well-tolerated by patients with HPV-positive oropharyngeal cancer. Research indicates that nonsmokers with this cancer type tend to have better survival rates, suggesting the treatment is effective and relatively safe for this group.

Although specific numbers on side effects aren't available, this treatment is widely used and considered safe enough for ongoing studies. For those considering joining a trial with cisplatin, these findings suggest a promising safety profile, particularly for individuals with HPV-related oropharyngeal cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for oropharyngeal cancer?

Researchers are excited about this treatment for HPV-positive oropharyngeal carcinoma because it combines standard radiation therapy with cisplatinum in a potentially less intense way. Unlike traditional approaches that often involve high-intensity chemotherapy, this treatment aims to reduce the intensity while maintaining effectiveness. This approach could minimize side effects and improve the quality of life for patients by offering a gentler, yet still powerful, alternative to the current standard of care.

What evidence suggests that this trial's treatments could be effective for oropharyngeal cancer?

Studies have shown that cisplatin effectively treats HPV-positive oropharyngeal cancer (OPSCC). Research indicates that patients receiving cisplatin with radiotherapy, the approach used in this trial, have better survival rates than those receiving treatments like cetuximab. One study found that after two years, 97.5% of patients who received cisplatin were still alive, compared to 90% of those who received another treatment. This finding suggests that cisplatin improves survival chances for people with this type of cancer. Therefore, cisplatin combined with standard radiation is considered a strong option for treating HPV-positive OPSCC. ^{6 7 8 9 10}

Who Is on the Research Team?

Kenneth S. Hu

Principal Investigator

NYU Langone Health

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Arm 4: Dose de-escalation (5 weeks) Experimental Treatment 2 Interventions

For participants who achieve both a favorable nodal response (\>40%) on interval CT scan as well as rapid ctHPV DNA clearance at week 4, radiation treatment will be further de-escalated to a total dose of 50 Gy/5 weeks with 5 doses of weekly cisplatinum).

Group II: Arm 3: Dose de-escalation (6 weeks) Experimental Treatment 2 Interventions

For participants who achieve (a) rapid nodal shrinkage on interval CT scan but slow / unknown ctHPV DNA clearance OR (b) slow nodal shrinkage on interval CT scan but rapid ctHPV DNA clearance at week 4, radiation treatment will be de-escalated to a total dose of 60Gy/6 weeks with 6 doses of weekly (cisplatinum). This arm replaced Arm 1.

Group III: Arm 1: Dose de-escalation (6 weeks) Experimental Treatment 2 Interventions

26 participants demonstrating a favorable response defined as \>40% nodal shrinkage were eligible to receive the de-escalated treatment regimen (6 doses of weekly cisplatinum with 6 weeks of radiation to a total dose of 60Gy). This arm is closed and has been replaced with Arm 3.

Group IV: Arm 2: Standard radiation therapy + cisplatinum (7 weeks) Active Control 3 Interventions

Participants will receive standard radiation therapy and cisplatinum for 7 weeks.

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+

Published Research Related to This Trial

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 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 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 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]

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]

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 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 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 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 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 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]

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]

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