IMRT +/− Cisplatin for Oropharyngeal Cancer

Recruiting at 258 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: NRG Oncology

Disqualifiers: Oral cavity cancer, Metastatic disease, Prior chemotherapy, Severe comorbidity, 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: Unknown

Duration: 5-6 weeks

316 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. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment IMRT +/− Cisplatin for Oropharyngeal Cancer?

Research shows that using cisplatin with intensity-modulated radiation therapy (IMRT) can help control tumors in head and neck cancers, including oropharyngeal cancer. Studies have compared different dosing schedules of cisplatin with IMRT, indicating its role in improving treatment outcomes. ^{1 2 3 4 5}

Is the combination of IMRT and Cisplatin safe for treating oropharyngeal cancer?

IMRT is shown to reduce late salivary gland damage without affecting tumor control in oropharyngeal cancer patients. Cisplatin, when used with IMRT, has been studied for its safety, with research focusing on the best dosing schedules to manage treatment side effects. ^{1 6 7 8 9}

How is the treatment of IMRT with or without Cisplatin unique for oropharyngeal cancer?

The combination of Cisplatin (a chemotherapy drug) with Intensity-Modulated Radiation Therapy (IMRT) is unique because it aims to enhance tumor control while reducing side effects like salivary gland damage, compared to conventional radiation techniques. This approach allows for precise targeting of the cancer, potentially improving patient outcomes and minimizing harm to surrounding healthy tissues. ^{1 2 3 6 9}

What is the purpose of this trial?

This randomized phase II trial studies the side effects and how well modestly reduced-dose intensity-modulated radiation therapy (IMRT) with or without cisplatin works in treating patients with oropharyngeal cancer that has spread to other places in the body (advanced). Radiation therapy uses high energy x rays to kill tumor cells. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether IMRT is more effective with or without cisplatin in treating patients with oropharyngeal cancer.

Research Team

Sue Yom

Principal Investigator

NRG Oncology

Eligibility Criteria

This trial is for adults with advanced oropharyngeal cancer, which includes cancers of the mouth and throat. Participants must have a specific type of squamous cell carcinoma confirmed by pathology, measurable disease, and positive p16 immunohistochemistry. They should be in good physical condition (Zubrod Performance Status 0-1), not exceed a 10 pack-year smoking history, and have proper organ function. HIV-positive patients can join if they meet certain health criteria.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

My blood, kidney, and liver tests are normal.

Imaging within 56 days prior to registration

Exclusion Criteria

My cancer has spread beyond its original site or I have swollen lymph nodes below my collarbone.

I have received chemotherapy for my current cancer.

Prior allergic reaction to cisplatin

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intensity-modulated radiation therapy (IMRT) for 5 or 6 weeks, with or without concurrent cisplatin chemotherapy

5-6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at 1 and 3 months, then every 3 months for 2 years, every 6 months for 3 years, and annually thereafter

5 years

Treatment Details

Interventions

• Cisplatin
• Intensity-Modulated Radiation Therapy

Trial Overview The study is testing whether reduced-dose intensity-modulated radiation therapy (IMRT) alone or combined with cisplatin chemotherapy is effective in treating advanced oropharyngeal cancer. Patients will be randomly assigned to receive either IMRT for 5 or 6 weeks with or without cisplatin to compare treatment outcomes.

Participant Groups

Group I: IMRT 6 weeks + cisplatin Experimental Treatment 2 Interventions

IMRT 6 weeks with concurrent cisplatin

Group II: IMRT 5 weeks Experimental Treatment 1 Intervention

IMRT 5 weeks

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?

NRG Oncology

Lead Sponsor

Trials

242

Recruited

105,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 60 patients with locally advanced head and neck squamous cell carcinoma (HNSCC), weekly low-dose cisplatin (30 mg/m2) resulted in significantly lower acute toxicities compared to high-dose cisplatin (100 mg/m2 every 3 weeks), with 56.6% of patients experiencing severe side effects versus 76.6% in the high-dose group.

While the low-dose regimen had better patient compliance (70% completing at least 6 doses) and lower toxicity, it also resulted in a lower loco-regional control rate (57.6%) compared to the high-dose group (72.8%), indicating a trade-off between safety and treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cisplatin Weekly Versus Every 3 Weeks Concurrently with Radiotherapy in the Treatment of Locally Advanced Head and Neck Squamous Cell Carcinomas: What Is the Best Dosing and Schedule? Mashhour, K., Hashem, W.[2020]

Intensity modulated radiation treatment (IMRT) for oropharyngeal squamous cell carcinoma showed excellent locoregional control, with a 3-year locoregional progression-free survival rate of 98.8% among 66 patients treated between 2000 and 2004.

Despite the high locoregional control, there was a concerning rate of distant metastasis, with a 3-year distant metastasis-free survival rate of only 80.4%, indicating a need for further research into systemic treatments for patients at risk of distant disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changing failure patterns in oropharyngeal squamous cell carcinoma treated with intensity modulated radiotherapy and implications for future research. Yao, M., Nguyen, T., Buatti, JM., et al.[2006]

In a study of 148 oropharynx cancer patients treated with either IMRT alone or a combination of IMRT and IMPT, the combination therapy showed significantly lower rates of severe acute toxicities, such as mucositis and pain, indicating a safer treatment option.

Despite similar overall survival and progression-free survival rates between the two groups, the IMRT/IMPT combination resulted in fewer patients experiencing grade ≥ 3 mucositis and pain, suggesting improved patient comfort during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Clinical Outcomes of Intensity Modulated Radiation Therapy/Intensity Modulated Proton Therapy Combination in Comparison with Intensity Modulated Radiation Therapy Alone in Oropharynx Cancer Patients. Yoon, HG., Ahn, YC., Oh, D., et al.[2021]

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 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]

Intensity-modulated radiation therapy (IMRT) significantly reduced the incidence of late xerostomia (dry mouth) in patients with oropharyngeal cancer compared to conventional radiation therapy (CRT), indicating a safety advantage for IMRT.

The study, which followed 430 patients over a median of 3.9 years, found that IMRT did not negatively affect tumor control or disease-free survival rates, demonstrating its efficacy in treating oropharyngeal carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiation therapy reduces late salivary toxicity without compromising tumor control in patients with oropharyngeal carcinoma: a comparison with conventional techniques. Chao, KS., Majhail, N., Huang, CJ., et al.[2022]

Intensity-modulated radiotherapy (IMRT) shows excellent local-regional control rates of 92% for patients with squamous cell carcinoma of the oropharynx, based on a study of 107 patients with a median follow-up of 29 months.

Despite the high local control, distant metastases were a significant concern, with 7 patients experiencing them as the first site of failure, highlighting the need for ongoing monitoring and potential additional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiotherapy in the treatment of oropharyngeal cancer: clinical outcomes and patterns of failure. Daly, ME., Le, QT., Maxim, PG., et al.[2022]

Intensity-modulated radiotherapy (IMRT) for oropharyngeal squamous cell carcinoma showed promising 5-year local control rates, with 87% overall and varying by cancer stage, indicating its efficacy in managing advanced disease.

The treatment resulted in a 5-year cause-specific survival rate of 85% and an overall survival rate of 76%, with a relatively low incidence of severe late complications (8%), suggesting that IMRT is a safe and effective option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiotherapy for oropharyngeal squamous cell carcinoma. Mendenhall, WM., Amdur, RJ., Morris, CG., et al.[2022]

References

1. Thailand pubmed.ncbi.nlm.nih.gov

Cisplatin Weekly Versus Every 3 Weeks Concurrently with Radiotherapy in the Treatment of Locally Advanced Head and Neck Squamous Cell Carcinomas: What Is the Best Dosing and Schedule? [2020]

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

Changing failure patterns in oropharyngeal squamous cell carcinoma treated with intensity modulated radiotherapy and implications for future research. [2006]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Early Clinical Outcomes of Intensity Modulated Radiation Therapy/Intensity Modulated Proton Therapy Combination in Comparison with Intensity Modulated Radiation Therapy Alone in Oropharynx Cancer Patients. [2021]

4. 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]

5. 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]

6. Ireland pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiation therapy reduces late salivary toxicity without compromising tumor control in patients with oropharyngeal carcinoma: a comparison with conventional techniques. [2022]

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

Intensity-modulated radiotherapy in the treatment of oropharyngeal cancer: clinical outcomes and patterns of failure. [2022]

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

Prediction of acute toxicity grade ≥ 3 in patients with locally advanced non-small-cell lung cancer receiving intensity modulated radiotherapy and concurrent low-dose Cisplatin. [2013]

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

Intensity-modulated radiotherapy for oropharyngeal squamous cell carcinoma. [2022]