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

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This study seeks to study the population of HPV-related oropharynx cancer patients that appear to be at highest risk for treatment failure with loco-regional failure and distant metastases including cT4 or cN3. The study team aims to determine if it is feasible to use multi-modality imaging (both DCE MRI and FDG-PET) to optimize the radiation boost in high risk p16+ OPSCC with similar or decreased toxicity compared to historic standard therapy.

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.

What data supports the effectiveness of the treatment for oropharyngeal cancer?

Research shows that combining chemotherapy with radiation can improve outcomes for patients with advanced oropharyngeal cancer. Specifically, using carboplatin with radiation has shown promising results, with some patients experiencing complete remission and the treatment being well tolerated. ^{1 2 3 4 5}

Is the combination of chemotherapy and radiation safe for treating oropharyngeal cancer?

The combination of chemotherapy and radiation, particularly with platinum-based drugs like cisplatin and carboplatin, has been used to treat oropharyngeal cancer. While some side effects like bone necrosis and laryngeal edema have been reported, they are generally considered tolerable, and no severe life-threatening toxicities were observed in the studies. ^{1 5 6 7 8}

How does the chemotherapy and radiation treatment for oropharyngeal cancer differ from other treatments?

This treatment combines platinum-based chemotherapy (using drugs like cisplatin or carboplatin) with radiation, which is more effective than radiation alone for advanced oropharyngeal cancer. Carboplatin may have fewer side effects compared to cisplatin, making it a potential alternative for patients who cannot tolerate cisplatin. ^{1 2 3 4 5}

Research Team

Michelle Mierzwa, M.D.

Principal Investigator

University of Michigan Rogel Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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 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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

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

2. India pubmed.ncbi.nlm.nih.gov

Simultaneous radiochemotherapy in the treatment of inoperable, locally advanced head and neck cancers. [2013]

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

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

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

Concurrent chemoradiation with carboplatin-5-fluorouracil versus cisplatin in locally advanced oropharyngeal cancers: is more always better? [2013]

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. England pubmed.ncbi.nlm.nih.gov

Clinical outcome of oropharyngeal carcinoma treated with platinum-based chemoradiotherapy. [2014]

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

Definitive radiochemotherapy of advanced head and neck cancer with carboplatin and paclitaxel : a phase II study. [2021]