Tailored Therapy for HPV-Related Oropharyngeal Cancer

Recruiting at 1 trial location

Overseen By Jonathan Schoenfeld, MD, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Jonathan Schoenfeld, MD, MPH

Disqualifiers: Metastatic disease, Prior head/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: 34

Duration: 5-8 weeks

145 Participants Needed

Trial Summary

What is the purpose of this trial?

This research is being conducted to understand if treatment can be tailored for participants with HPV-related oropharynx cancers using both clinical features (stage of the tumor, smoking status) combined with an investigational HPV blood test. The names of the test and treatments involved in this study are: * NavDx® HPV ctDNA testing (HPV blood test) * Radiation therapy * Chemotherapy: Cisplatin, or Carboplatin and Paclitaxel (not all participants receive any or all of these agents)

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 to get specific guidance based on your situation.

What data supports the effectiveness of the treatment for HPV-related oropharyngeal cancer?

Research shows that cisplatin, when used with radiation therapy, is effective for treating HPV-positive oropharyngeal cancer, with better outcomes compared to cetuximab. This combination is considered the standard treatment for this type of cancer. ^{1 2 3 4 5}

Is the treatment for HPV-related oropharyngeal cancer safe?

Cisplatin, often used with radiation therapy for HPV-related oropharyngeal cancer, is known to cause long-term side effects, which has led to exploring other treatments like carboplatin that might have fewer side effects. Radiation therapy alone is also considered, but it can still cause significant long-term toxicity. ^{3 4 5 6 7}

How is the treatment with Cisplatin, Paclitaxel, and Radiotherapy unique for HPV-related oropharyngeal cancer?

This treatment is unique because it combines Cisplatin and Paclitaxel with Radiotherapy, which is different from other approaches that might use Cetuximab instead of Cisplatin to reduce side effects. Cisplatin is often preferred for its effectiveness, especially in HPV-positive cases, despite its higher toxicity compared to alternatives like Cetuximab. ^{2 3 5 8 9}

Research Team

Jonathan D. Schoenfeld, MD MPH

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

Adults aged 22+ with HPV-related oropharyngeal cancer (stage I-III, excluding N3 disease) who have not had prior head and neck cancer treatments. Participants must be able to provide blood samples, have adequate organ function for chemotherapy, and use effective contraception if of childbearing potential.

Inclusion Criteria

I am willing to give blood and tissue samples for the study.

I am a man who will use highly effective birth control if having sex with women who can get pregnant.

My cancer is HPV-related, in my throat (tongue or tonsil), and not the most advanced stage.

Exclusion Criteria

I have another cancer that is getting worse or needs treatment.

My HPV test by NavDx® shows no HPV DNA or only types 18, 31, 33, or 35.

I have had cancer surgery in my head or neck area before radiation or chemoradiation.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive radiation therapy and possibly chemotherapy based on risk assessment using HPV ctDNA testing

5-8 weeks

Weekly visits for radiation therapy, chemotherapy every 21 days or weekly

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Every 12 weeks for the first 2 years, then every 24 weeks in year 3

Treatment Details

Interventions

• Cisplatin
• NavDx HPV ctDNA Testing
• Paclitaxel
• Radiotherapy

Trial Overview The study is testing personalized treatment plans using clinical features and an investigational HPV blood test called NavDx®. It involves radiation therapy combined with chemotherapy drugs like Cisplatin or Carboplatin and Paclitaxel based on the individual's tumor DNA profile.

Participant Groups

Group I: LOW RISK RT (ALONE OR WITH SOC CHEMO Experimental Treatment 3 Interventions

The research study procedures include: screening for eligibility, and study treatments including evaluations and follow-up visits * NavDx HPV ctDNA Testing: Blood will be collected and shared with an outside lab for analysis (less than 10 mL of blood or about 2 teaspoons). The results of this test will determine what radiation dose received . The specimens will be de-identified. The specimens will be banked for future use. * Radiation Therapy: Lower risk participants will receive a lower dose and treatment will only last 5-6 weeks. * Chemotherapy: Chemotherapy and radiation therapy are both considered standard treatments for your type of cancer. The study doctor will decide whether or not chemotherapy with radiation and the type of chemotherapy. * Bolus Cisplatin: Infused every 21 days for up to 2 or 3 doses. * Weekly Cisplatin or Carboplatin with Paclitaxel: Infused weekly during radiation therapy

Group II: INTERMEDIATE RISK RT (ALONE OR WITH SOC CHEMO Experimental Treatment 3 Interventions

The research study procedures include: screening for eligibility, and study treatments including evaluations and follow-up visits * NavDx HPV ctDNA Testing: Blood will be collected and shared with an outside lab for analysis (less than 10 mL of blood or about 2 teaspoons). The results of this test will determine what dose of radiation received. The specimens will be de-identified. The specimens will be banked for future use. * Radiation Therapy: Higher risk participants will receive standard radiation dose for up to 7-8 weeks * Chemotherapy: Chemotherapy and radiation therapy are both considered standard treatments for your type of cancer. The study doctor will decide whether or not chemotherapy with radiation and the type of chemotherapy. * Bolus Cisplatin: Infused every 21 days for up to 2 or 3 doses. * Weekly Cisplatin or Carboplatin with Paclitaxel: Infused weekly during radiation therapy

Cisplatin 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
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

Jonathan Schoenfeld, MD, MPH

Lead Sponsor

Trials

1

Recruited

150+

Naveris

Collaborator

Trials

3

Recruited

260+

Findings from Research

In patients with stage III to IVb HPV-positive oropharyngeal cancer, active smokers had a significantly higher rate of distant metastases (22%) compared to never or former smokers (5%), indicating smoking status is a critical predictor of cancer progression.

Patients with T4 tumors also showed increased rates of distant metastases (15%) compared to those with T1 to T3 tumors (6%), and those treated with cetuximab-based bioradiotherapy had a higher rate of metastases (23%) compared to those receiving cisplatin-based chemoradiotherapy (5%), suggesting the need for intensified treatment strategies for these high-risk groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of distant metastasis in human papillomavirus-associated oropharyngeal cancer. Weller, MA., Ward, MC., Berriochoa, C., et al.[2018]

In a study of 1,149 patients with advanced head and neck squamous cell carcinoma, carboplatin-based chemoradiotherapy showed similar cancer-specific mortality rates compared to cisplatin-based therapy, indicating that carboplatin can be an effective alternative for patients unable to receive cisplatin.

Both carboplatin and cisplatin-based chemoradiotherapy were found to be more effective than radiation therapy alone or radiation with cetuximab, suggesting that carboplatin should be further investigated as a viable treatment option for certain patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival After Definitive Chemoradiotherapy With Concurrent Cisplatin or Carboplatin for Head and Neck Cancer. Xiang, M., Colevas, AD., Holsinger, FC., et al.[2020]

In a phase 3 trial involving 334 patients with HPV-positive low-risk oropharyngeal cancer, cetuximab did not reduce severe toxicity compared to cisplatin, with both treatments showing similar rates of severe side effects at 24 months.

However, cetuximab was associated with significantly worse outcomes in terms of overall survival (89.4% vs 97.5%) and recurrence rates (16.1% vs 6.0%) compared to cisplatin, indicating that cisplatin remains the preferred treatment for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): an open-label randomised controlled phase 3 trial. Mehanna, H., Robinson, M., Hartley, A., et al.[2023]

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]

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]

A phase 2 trial involving 39 patients with HPV-related oropharyngeal squamous cell carcinoma showed that intensity-modulated radiation therapy (IMRT) alone resulted in a 90% complete response rate, indicating high efficacy without chemotherapy.

The treatment demonstrated a 2-year progression-free survival rate of 94% and a 100% overall survival rate, with manageable toxicity, as only 26% experienced severe mucositis and no long-term severe adverse effects were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation Therapy Alone for Human Papillomavirus-Related Squamous Cell Carcinoma of the Oropharynx: A Single-Arm, Phase 2 Study. Takemoto, N., Seo, Y., Nakahara, S., et al.[2021]

In a study of 421 patients with HPV-associated oropharyngeal squamous cell carcinoma, high-dose cisplatin (HDC) showed better outcomes for stage III disease, including lower rates of locoregional recurrence and distant metastasis, as well as improved overall survival compared to triweekly carboplatin (TC).

However, HDC was associated with significantly higher toxicity, including increased rates of severe leukopenia and weight loss, suggesting that TC may be a safer option for patients with early-stage disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Triweekly carboplatin as a potential de-intensification agent in concurrent chemoradiation for early-stage HPV-associated oropharyngeal cancer. Iganej, S., Beard, BW., Chen, J., et al.[2020]

In a meta-analysis of 8 studies involving 1665 patients, treatment with cisplatin (CDDP) combined with radiotherapy resulted in significantly better overall survival (OS) and lower rates of locoregional recurrence (LRR) compared to cetuximab (C225) with radiotherapy for HPV-positive oropharyngeal cancer.

Patients receiving CDDP had a 2.2-fold lower risk of death and a 2.9-fold lower risk of locoregional recurrence, indicating that CDDP-based chemoradiotherapy should remain the standard treatment for p16-positive oropharyngeal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cisplatin-based chemoradiotherapy vs. cetuximab-based bioradiotherapy for p16-positive oropharyngeal cancer: an updated meta-analysis including trials RTOG 1016 and De-ESCALaTE. Suton, P., Skelin, M., Rakusic, Z., et al.[2020]

In a study of 31 patients with low-risk HPV-positive oropharyngeal squamous cell carcinoma, treatment with weekly cisplatin and radiotherapy resulted in excellent disease control, with no recurrences or deaths reported during a median follow-up of 30 months.

The treatment was generally well-tolerated, with 84% of patients completing at least 5 cycles of cisplatin, although 71% experienced grade 3 mucositis, indicating some side effects but no need for enteral feeding at 12 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weekly cisplatin and radiotherapy for low risk, locoregionally advanced human papillomavirus-positive oropharyngeal squamous cell carcinoma. Urban, D., Corry, J., Solomon, B., et al.[2018]

References

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

Predictors of distant metastasis in human papillomavirus-associated oropharyngeal cancer. [2018]

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

Survival After Definitive Chemoradiotherapy With Concurrent Cisplatin or Carboplatin for Head and Neck Cancer. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): an open-label randomised controlled phase 3 trial. [2023]

4. England pubmed.ncbi.nlm.nih.gov

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

5. 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]

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

Radiation Therapy Alone for Human Papillomavirus-Related Squamous Cell Carcinoma of the Oropharynx: A Single-Arm, Phase 2 Study. [2021]

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

Triweekly carboplatin as a potential de-intensification agent in concurrent chemoradiation for early-stage HPV-associated oropharyngeal cancer. [2020]

8. Germany pubmed.ncbi.nlm.nih.gov

Cisplatin-based chemoradiotherapy vs. cetuximab-based bioradiotherapy for p16-positive oropharyngeal cancer: an updated meta-analysis including trials RTOG 1016 and De-ESCALaTE. [2020]

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

Weekly cisplatin and radiotherapy for low risk, locoregionally advanced human papillomavirus-positive oropharyngeal squamous cell carcinoma. [2018]