Reduced Dose Radiotherapy for Oropharyngeal Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Icahn School of Medicine at Mount Sinai

Disqualifiers: Pregnancy, Other malignancies, Neuropathy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a lower dose of radiation can treat HPV-positive oropharyngeal cancer (a type of throat cancer) as effectively as the standard higher dose. Participants will receive either a reduced dose of radiation or the standard dose, both combined with the chemotherapy drug Carboplatin. The goal is to determine if the reduced dose provides the same benefits with potentially fewer side effects. Suitable candidates have HPV-positive oropharyngeal cancer at Stage 3 or 4, with no prior surgery, radiation, or chemotherapy for their cancer. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, you cannot be on any other anticancer therapy while participating in this trial.

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

Research has shown that using a lower dose of radiation to treat HPV-positive oropharyngeal cancer is generally well-tolerated. In earlier studies, oral mucositis, which causes soreness or swelling in the mouth, was the most common side effect, affecting about 36.4% of patients. A decrease in white blood cell count occurred in 30.5% of cases. This suggests that while side effects can occur, many people find them manageable.

Carboplatin, a chemotherapy drug often used with radiation, has been approved for treating other cancers. This provides existing safety information, and it is generally considered safe when used correctly. However, like any treatment, it can have side effects.

Overall, both reduced-dose radiation and carboplatin have undergone extensive study. While some risks exist, many patients find these treatments tolerable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the reduced dose radiotherapy for oropharyngeal cancer because it offers a potentially safer option with fewer side effects compared to the standard dose. Unlike traditional treatments that use a higher radiation dose of 7000 cGy, this approach uses a reduced dose of 5600 cGy while still incorporating carboplatin. The aim is to maintain effectiveness in fighting cancer while reducing the risk of harmful side effects often associated with higher radiation levels. This could mean a better quality of life during and after treatment for patients.

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

Research has shown that lowering radiation doses for HPV-related throat cancer can reduce treatment side effects while remaining effective. In this trial, participants will receive either a reduced dose of radiation or a standard dose, determined randomly. Studies have found that a lower radiation dose maintains good survival rates without affecting the main treatment outcomes. Specifically, patients experienced fewer long-term side effects, improving their quality of life. This suggests that using less radiation could effectively treat this type of cancer without compromising effectiveness. ^{1 2 6 7 8}

Who Is on the Research Team?

Marshall R. Posner

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

Adults over 18 with HPV-positive oropharyngeal cancer, who haven't had previous cancer treatments and are in good physical condition. They must not be pregnant, have no other current cancers (with some exceptions), and can't have a history of significant alcohol or drug abuse within the last six months.

Inclusion Criteria

No active alcohol addiction (as assessed by medical caregiver and defined as at least 6 months without activity)

I have Gilbert's Disease but no liver damage, and my liver tests are normal except for high bilirubin.

My cancer is HPV positive and confirmed by specific tests.

Exclusion Criteria

I have no other cancers, except possibly treated skin, cervical, or thyroid cancer with no signs for 5 years.

Other serious illnesses or medical conditions including but not limited to: unstable cardiac disease despite treatment, myocardial infarction within 6 months prior to study entry, history of significant neurologic or psychiatric disorders including dementia or seizures, active clinically significant uncontrolled infection, active peptic ulcer disease defined as unhealed or clinically active, hypercalcemia, active drug addiction including alcohol, cocaine or intravenous drug use defined as occurring within the 6 months preceding diagnosis, chronic obstructive pulmonary disease, autoimmune disease requiring therapy, prior organ transplant, or HIV infection, interstitial lung disease, hepatitis C (test required), patients that have experienced an involuntary weight loss of more than 25% of their body weight in the 2 months preceding study entry, concurrent treatment with any other anticancer therapy, participation in an investigational therapeutic drug trial within 30 days of study entry, active smoking within the past 20 years with a cumulative Pack Year history of > 20 Pack Years or active smoking (Defined as > 1 cigarette per day) within the last 2 years

I have significant hearing loss.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Chemotherapy

Participants receive three cycles of Docetaxel, Cisplatin, and 5-FU (TPF) induction chemotherapy

9 weeks

3 cycles

Radiation Therapy

Participants undergo randomization to receive either reduced (5600 cGy) or standard (7000 cGy) dose radiotherapy with weekly Carboplatin

6-7 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Reduced Dose Radiation
• Standard Dose Radiation

Trial Overview The trial is testing if a lower dose of radiation combined with Carboplatin is as effective as the standard higher dose for treating HPV-related throat cancer. Patients will be compared based on local-regional control and progression-free survival after three years.

How Is the Trial Designed?

Group I: Reduced Dose Radiation Experimental Treatment 2 Interventions

Patients randomized to receive a reduced (5600 cGy) dose radiotherapy with weekly Carboplatin

Group II: Standard Dose Radiation Active Control 2 Interventions

Patients randomized to receive a standard (7000 cGy) dose radiotherapy with carboplatin

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

Approved in United States as Paraplatin for:

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

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

Biodesign Institute

Collaborator

Trials

1

Recruited

20+

The Biodesign Institute

Collaborator

Trials

1

Recruited

20+

Arizona State University

Collaborator

Trials

311

Recruited

109,000+

Published Research Related to This Trial

In a phase II trial involving 25 patients with advanced head and neck cancer, carboplatin demonstrated clinical activity, with 24% of patients achieving an objective response, including two complete responses.

The drug was generally well-tolerated, with mild side effects such as nausea, vomiting, and myelosuppression, and no significant renal or neurologic toxicity reported, suggesting it may be a safe treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin, an active drug in advanced head and neck cancer. de Andres Basauri, L., Lopez Pousa, A., Alba, E., et al.[2013]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9843369/

Reduced-dose radiation in human papillomavirus ... Reducing the radiation dose in patients with HPV-related OPC substantially alleviates the treatment toxicities and optimizes the quality of life of patients.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01706939

NCT01706939 | The Quarterback Trial: Reduced Dose ... This trial aims to directly compare a reduced radiation dose to the standard of care in HPVOPC for non-inferiority, thus allowing for direct comparison of ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S136883752500483X

long-term follow-up of the quarterback de-escalation trials The results of the de-escalated radiation regimen in patients with molecularly-proven HPVOPC reduced long-term toxicity without compromising survival [[24], [25] ...

4. practicalradonc.org practicalradonc.org/article/S1879-8500(24)00139-5/fulltext

Radiation Therapy for HPV-Positive Oropharyngeal ... For most patients with oropharyngeal cancer, a mean dose <2000 cGy in the ipsilateral or node-positive neck and dose <500 cGy in the ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1368837519302106

Standard of care vs reduced-dose chemoradiation after ... We hypothesized that a dose of 5600 cGy, compared to the standard 6900–7200 cGy of definitive radiotherapy, would be reasonably expected to be as effective and ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01706939

NCT01706939 | The Quarterback Trial: Reduced Dose ... This trial aims to directly compare a reduced radiation dose to the standard of care in HPVOPC for non-inferiority, thus allowing for direct comparison of ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0360301619307461

Palliative Radiation Therapy for Head and Neck Cancers This review presents the treatment approaches, outcomes, and toxicities associated with different radiation regimens and proposes a multidisciplinary framework

8. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.21622

Oral mucositis in patients undergoing radiation treatment for ... The majority of patients (83%) received standard radiation therapy; the mean (± SD) cumulative dose was 6285 centigrays (cGy) (± 1158 cGy).