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

23 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment Reduced Dose Radiotherapy for Oropharyngeal Cancer?

Research shows that combining carboplatin with radiation therapy can lead to promising results in treating advanced oropharyngeal cancer, with some studies reporting a complete remission in 60% of patients. This suggests that using carboplatin with reduced dose radiotherapy might also be effective. ^{1 2 3 4 5}

Is reduced dose radiotherapy with carboplatin safe for treating oropharyngeal cancer?

Carboplatin, when used with radiotherapy for head and neck cancers, generally has mild side effects like nausea and vomiting, with more serious blood-related side effects (myelosuppression) occurring at higher doses. The treatment is usually well tolerated, although some patients may experience severe mouth sores (mucositis) that can interrupt treatment. ^{1 2 3 6 7}

How does the reduced dose radiotherapy treatment for oropharyngeal cancer differ from other treatments?

This treatment is unique because it uses a reduced dose of radiation combined with carboplatin, which has similar effects to the standard cisplatin but with potentially fewer side effects. The reduced radiation dose aims to maintain effectiveness while minimizing harmful side effects, making it a potentially safer option for patients. ^{1 2 4 7 8}

What is the purpose of this trial?

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 outcomes between the two groups. The study hypothesis is that LRC and PFS at 3 years for reduced dose CRT are non-inferior to standard dose CRT.

Research Team

Marshall R. Posner

Principal Investigator

Icahn School of Medicine at Mount Sinai

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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 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]

References

1. India pubmed.ncbi.nlm.nih.gov

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

2. England pubmed.ncbi.nlm.nih.gov

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

3. 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]

4. Germany pubmed.ncbi.nlm.nih.gov

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

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

Simultaneous integrated boost using intensity-modulated radiotherapy compared with conventional radiotherapy in patients treated with concurrent carboplatin and 5-fluorouracil for locally advanced oropharyngeal carcinoma. [2018]

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

Carboplatin, an active drug in advanced head and neck cancer. [2013]

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

Phase I/II study of simultaneous carboplatin and radiotherapy in unresectable squamous cell carcinoma of the head and neck. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Phase I/II study of concurrent weekly carboplatin and radiation therapy in advanced head and neck cancer. [2019]