Chemotherapy + Radiation for Oropharyngeal Cancer

(ARTHOUSE Trial)

Overseen By Michelle Mierzwa

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Michigan Rogel Cancer Center

Disqualifiers: Pregnancy, Prior invasive malignancy, 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: 35

Duration: 7 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial seeks better treatments for HPV-related oropharyngeal cancer, which affects the throat area. Researchers are testing whether advanced imaging techniques can more effectively target radiation in patients at high risk of the cancer spreading or returning. The trial combines standard platinum-based chemotherapy with radiation. It seeks participants with advanced p16+ oropharyngeal cancer who have not received prior treatment for this cancer. Ideal candidates can undergo both chemotherapy and radiation and meet specific health criteria. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to advancements in cancer care.

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 study team or your doctor.

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

Research shows that platinum-based chemotherapy is generally safe, though it can cause side effects. Studies have demonstrated good survival rates for patients receiving this treatment. However, some individuals might experience side effects like nausea and low blood cell counts.

Radiation therapy is also widely used and well understood. Patients with oropharyngeal cancer may experience side effects such as a sore throat and dry mouth. Fortunately, modern techniques have reduced these issues.

Both treatments are commonly used for cancer and have been extensively studied. They work well together. While risks exist, many patients manage them effectively. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment combination because it aims to enhance the effectiveness of standard therapy for oropharyngeal cancer. Unlike traditional protocols that use either chemotherapy or radiation alone, this approach combines weekly platinum-based chemotherapy with daily radiation, specifically targeting high-risk areas with a precise dose of 70 Gy. This dual approach not only maximizes the cancer-killing effects but also aims to improve patient outcomes by potentially offering more comprehensive control over tumor growth.

What evidence suggests that chemotherapy and radiation could be effective for oropharyngeal cancer?

In this trial, patients will receive a combination of platinum-based chemotherapy and radiation therapy as part of the treatment arm. Research has shown that platinum-based chemotherapy effectively treats cancers like oropharyngeal cancer by damaging the DNA of cancer cells, stopping their growth and spread. Studies have found that patients receiving this type of chemotherapy often live longer.

Radiation therapy, another component of this trial, plays a crucial role in treating oropharyngeal cancer. It uses high-energy rays to target and destroy cancer cells. Some studies have reported survival rates between 60% and 75% for patients treated with advanced radiation methods like intensity-modulated radiation therapy (IMRT). Using these treatments together has improved outcomes for patients with aggressive forms of this cancer. ^{1 2 3 4 5}

Who Is on the Research Team?

Michelle Mierzwa, M.D.

Principal Investigator

University of Michigan Rogel Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with advanced HPV-related squamous cell carcinoma of the oropharynx, specifically stage III (cT4 or N3). Participants must be in good physical condition (ECOG 0-1), have certain blood and liver function levels within normal ranges, and be able to receive chemotherapy. Women who can bear children and men must use effective birth control during the study.

Inclusion Criteria

I have been mostly active and able to carry out all my pre-disease activities up to two weeks before joining.

I am older than 18.

My cancer is at an advanced stage but has not spread to distant organs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive radiation therapy with a prescription of 70 Gy to PTVhigh in 35 fractions, along with weekly platinum chemotherapy

7 weeks

35 visits (in-person, daily)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including biomarker analysis and imaging

up to 3 years

Surveillance

Monitoring of HPV ctDNA biomarkers in urine and blood, and oral microbiome analysis

up to 24 months

What Are the Treatments Tested in This Trial?

Interventions

• Platinum-based chemotherapy
• Radiation

Trial Overview The study is testing whether using detailed imaging techniques like DCE MRI and FDG-PET to guide radiation therapy can improve outcomes for high-risk throat cancer patients while maintaining or reducing treatment side effects compared to standard therapies.

How Is the Trial Designed?

Group I: Treatment Arm Experimental Treatment 2 Interventions

Patients will initially receive a single prescription of 70 Gy to PTVhigh in 35 fractions with RT given once daily, 5 days a week along with weekly platinum (standard therapy). All fields must be treated daily. On days when chemotherapy is given, it will be administered prior to RT. Prescription to high risk PTV will be 70Gy in 35 fractions and to PTV2 will be 56Gy in 35 fractions.

Platinum-based chemotherapy is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Platinum-based chemotherapy for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Bladder cancer

Approved in United States as Platinum-based chemotherapy for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Bladder cancer
• Cervical cancer

Approved in Canada as Platinum-based chemotherapy for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Bladder cancer

Approved in Japan as Platinum-based chemotherapy for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Bladder cancer
• Stomach cancer

Who Is Running the Clinical Trial?

University of Michigan Rogel Cancer Center

Lead Sponsor

Trials

303

Recruited

20,700+

Published Research Related to This Trial

In a study of 84 patients with advanced squamous cell carcinomas of the oropharynx and hypopharynx, concurrent treatment with carboplatin and paclitaxel alongside radiotherapy showed a 2-year overall survival rate of 46.3% and a progression-free survival rate of 41.0%.

The treatment was associated with significant acute toxicity, with 51.2% of patients experiencing severe mucositis and 6% experiencing severe leucopenia and thrombopenia, indicating that while the treatment is effective, it can also lead to considerable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Definitive radiochemotherapy of advanced head and neck cancer with carboplatin and paclitaxel : a phase II study. Semrau, R., Temming, S., Preuss, SF., et al.[2021]

In a study of 91 patients treated with platinum-based chemoradiotherapy for oropharyngeal carcinoma, the 5-year overall survival rate was 66%, indicating effective long-term outcomes for this treatment.

The treatment demonstrated good local control with a 5-year local control rate of 79%, and while some patients experienced late toxicities, they were generally tolerable, with no severe grade 5 toxicities reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcome of oropharyngeal carcinoma treated with platinum-based chemoradiotherapy. Nakamura, T., Kodaira, T., Tachibana, H., et al.[2014]

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 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]

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 study of 253 patients with locally advanced oropharyngeal cancer, both carboplatin-5-fluorouracil and high-dose cisplatin regimens showed similar efficacy in terms of overall survival, disease-free survival, and locoregional control rates after 3 years.

The 3-year overall survival rates were 79.1% for carboplatin-5FU and 74.9% for cisplatin, indicating that both chemotherapy regimens are effective options for treatment, with no significant differences found between them.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent chemoradiation with carboplatin-5-fluorouracil versus cisplatin in locally advanced oropharyngeal cancers: is more always better? Barkati, M., Fortin, B., Soulières, D., et al.[2013]

In a study of 20 patients with inoperable stage III and IV oral or oropharyngeal cancers, the combination of carboplatin and radiation therapy resulted in a 60% complete remission rate, indicating significant efficacy in treating these advanced cancers.

The treatment was well tolerated, with only 2 patients experiencing severe side effects that required interruptions, suggesting that carboplatin can be safely integrated into chemoradiation regimens for head and neck cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simultaneous radiochemotherapy in the treatment of inoperable, locally advanced head and neck cancers. Awasthy, BS., Julka, PK., Rath, GK., et al.[2013]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6892396/

Comparing Outcomes of Concurrent Chemotherapy ... Patients who received CDDP had improved OS. CDDP was also associated with slightly lower overall costs and higher antiemetic usage and hospital visit rates.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9169397/

Comparing the efficacy and safety of cisplatin and other ... The results showed that some cisplatin-based neoadjuvant chemotherapy regimens improved the prognosis of patients with NPC and reduced the toxicity of ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2772906024005193

Systematic analysis of chemotherapy, immunotherapy, and ... The rationale behind platinum-based chemotherapy is its ability to induce DNA crosslinking, which prevents DNA replication and transcription, ultimately leading ...

4. thegreenjournal.com thegreenjournal.com/article/S0167-8140(22)04234-7/fulltext

Disease outcome and associated factors after definitive ... Retrospective data were collected from a multicenter cohort of 513 patients treated with definitive concurrent platinum-based CRT with curative ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa0802656

Platinum-Based Chemotherapy plus Cetuximab in Head ... The median overall survival of 7.4 months in the chemotherapy-alone group is consistent with the results of other randomized trials. The best overall ...