High-Dose vs Low-Dose Cisplatin with Radiation for Head and Neck Cancer

Not currently recruiting at 431 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: NRG Oncology

Disqualifiers: Oral cavity cancer, Metastatic disease, 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: 5

Duration: 7 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two approaches to using cisplatin with radiation therapy for advanced head and neck cancer. Researchers aim to determine if weekly cisplatin administration manages side effects better than the three-week schedule while maintaining effectiveness in extending life. Cisplatin, a chemotherapy drug, kills or slows cancer cells, and radiation therapy uses high-energy rays to target tumors. Individuals with metastatic head and neck cancer who have not received prior chemotherapy for this cancer may qualify for the study. As a Phase 2, Phase 3 trial, it evaluates treatment effectiveness in an initial group and represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking cancer 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. It's best to discuss your specific medications with the trial team to understand any potential interactions with cisplatin and radiation therapy.

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

Research has shown that both high-dose and low-dose cisplatin, when combined with radiation therapy, are generally well-tolerated by patients. Studies have found that the standard high-dose cisplatin, administered every three weeks, is effective but often causes significant side effects like hearing loss. In contrast, low-dose cisplatin given weekly usually results in less hearing damage, making it potentially easier on the ears.

A study comparing these two dosing schedules found no major differences in overall side effects, although low-dose cisplatin may lead to less severe hearing loss. However, side effects such as painful swelling, mouth sores (mucositis), and difficulty swallowing were more common with the high-dose schedule.

Overall, both dosing strategies appear safe, but each has its own set of side effects. This information can guide decisions based on individual tolerance and side effect preferences. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they explore different dosing schedules of cisplatin combined with radiation therapy for head and neck cancer. Unlike most treatments that typically involve a standard dosing frequency, this trial compares a high-dose regimen given every three weeks against a more frequent, lower-dose weekly regimen. By investigating these two strategies, researchers aim to find out if adjusting the timing and dosage can improve effectiveness and reduce side effects, potentially offering a more personalized approach to treatment. This exploration could lead to better outcomes and quality of life for patients with head and neck cancer.

What evidence suggests that this trial's treatments could be effective for head and neck cancer?

This trial will compare high-dose versus low-dose cisplatin combined with radiation therapy for head and neck cancer. Research has shown that both weekly and every three-week cisplatin treatments, when combined with radiation therapy, are effective for this type of cancer. Participants in Arm I will receive radiation therapy with every three-week cisplatin, while those in Arm II will receive radiation therapy with weekly cisplatin. Studies indicate that both schedules offer similar survival rates and safety. One study found that survival outcomes are comparable, but the every three-week schedule tends to cause more severe side effects. For weekly cisplatin, completion rates can vary, but the overall survival rate is about 72%. Choosing between the two options may depend on how well a patient tolerates the treatment, as both aim to shrink or control the cancer effectively. ^{6 7 8 9 10}

Who Is on the Research Team?

Paul M Harari

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

Adults with advanced head and neck cancer, including oral, laryngeal, oropharyngeal cancers but not oral cavity or nasopharynx cancers. Participants must have measurable disease, no history of cisplatin treatment for the current cancer, no distant metastases, and organ function within certain limits. HIV-positive patients are eligible if well-controlled. Pregnant or nursing individuals are excluded.

Inclusion Criteria

- One of the following imaging studies is required within 60 days prior to registration:

Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 1.5 x institutional ULN (within 30 days prior to registration)

Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (within 30 days prior to registration) (not applicable to patients with known Gilbert's syndrome)

Exclusion Criteria

I have had chemotherapy for this cancer but not with cisplatin.

You have a serious health condition that is currently active.

I am not pregnant or nursing, or I am willing to stop nursing.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive radiation therapy and cisplatin. In Arm I, cisplatin is administered every 3 weeks, and in Arm II, it is administered weekly.

7 weeks

5 visits per week for radiation therapy

Follow-up

Participants are monitored for safety, effectiveness, and toxicity after treatment, including assessments of overall survival and progression-free survival.

Up to 9 years

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• Radiation Therapy

Trial Overview The trial is comparing two dosing schedules of cisplatin chemotherapy combined with radiation therapy to treat locoregionally advanced head and neck cancer: high-dose every three weeks versus low-dose weekly. The goal is to determine which regimen offers better outcomes.

How Is the Trial Designed?

Group I: Arm II (radiation therapy, weekly cisplatin) Experimental Treatment 7 Interventions

Patients undergo radiation therapy over 5 fractions a week for a total of 33-35 fractions in the absence of disease progression or unacceptable toxicity. Patients also receive weekly cisplatin IV QW for 7 weeks during radiation therapy in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, or MRI or PET scan throughout the study.

Group II: ARM I (radiation therapy, every 3 week cisplatin) Active Control 7 Interventions

Patients undergo radiation therapy over 5 fractions a week for a total of 33-35 fractions in the absence of disease progression or unacceptable toxicity. Patients also receive cisplatin IV once Q3W (on days 1, 22, and 43) during radiation therapy in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, or MRI or PET scan throughout the study.

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+

Published Research Related to This Trial

In a study of 53 patients with untreated head and neck cancer, weekly cisplatin (40 mg/m²) combined with radiotherapy resulted in a high 2-year overall survival rate of 93.7% and a local progression-free rate of 88.0%.

The weekly regimen was associated with manageable toxicity, with 96.2% of patients completing the full course of radiotherapy, suggesting that this approach may be safer and easier to monitor compared to the traditional high-dose three-weekly cisplatin regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concomitant weekly cisplatin and radiotherapy for head and neck cancer. Homma, A., Inamura, N., Oridate, N., et al.[2022]

In a study of 142 patients with high-risk head and neck squamous cell carcinoma, postoperative radiotherapy combined with low-dose cisplatin (75 mg/m² every 3 weeks) resulted in a 5-year overall survival rate of 68%, indicating its efficacy as a treatment option.

While the treatment showed lower toxicity compared to higher doses of cisplatin, with 53% experiencing severe mucositis and 14% facing grade 3 hematologic toxicity, only 48% of patients completed all planned chemotherapy cycles, highlighting challenges in treatment adherence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative reduced dose of cisplatin concomitant with radiation therapy in high- risk head and neck squamous cell carcinoma. Franchin, G., Minatel, E., Politi, D., et al.[2013]

In a study involving 17 patients with head and neck squamous cell carcinoma, treatment with cis-diamminedichloroplatinum (CDDP) at a dose of 2.5 mg/kg resulted in one complete response and five partial responses, indicating its potential efficacy as a treatment.

The treatment was associated with only moderate toxicity, suggesting that CDDP may be a relatively safe option for patients with this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cis-disamminedichloroplatinum (II) CDDP: single agent in the treatment of advanced head and neck squamous cell carcinoma. Tranter, RM., Howell, A.[2019]

In a study of 83 head and neck cancer patients, a three-weekly chemotherapy schedule (cisplatin 100 mg/m2) resulted in less overall toxicity compared to a weekly schedule (cisplatin 40 mg/m2), particularly in terms of severe mucositis and treatment interruptions.

The weekly chemotherapy regimen was associated with higher rates of grade III skin and hematological toxicity, suggesting that while it may be effective, it poses greater risks of acute side effects compared to the three-weekly approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of acute toxicities of two chemotherapy schedules for head and neck cancers. Geeta, SN., Padmanabhan, TK., Samuel, J., et al.[2022]

Carboplatin and cisplatin both provide a survival benefit when used alongside radiation therapy for patients with locally advanced head and neck squamous cell carcinoma, with cisplatin showing potentially greater activity but carboplatin being better tolerated.

The most commonly used regimen for cisplatin is 100 mg/m² every 3 weeks during radiation therapy, although there is no consensus on the optimal total dose needed for effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In squamous cell head and neck cancer: which platinum, how much and how often? Nwizu, T., Adelstein, DJ.[2019]

In a study involving 225 patients with locally advanced head and neck squamous cell cancer, both high-dose cisplatin and a weekly cisplatin-paclitaxel regimen showed similar complete response rates of 88%.

The weekly cisplatin-paclitaxel regimen resulted in significantly lower acute and chronic toxicities compared to high-dose cisplatin, making it a safer alternative for patients who cannot tolerate cisplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing high-dose cisplatin with cisplatin-based combination chemotherapy in definitive concurrent chemoradiation setting for locally advanced head and neck squamous cell carcinoma (LAHNSCC). Furqan, M., Snyders, TP., Saqlain, MU., et al.[2021]

In a pilot study involving three patients with advanced head and neck cancer, the combination of radiation therapy and cisplatin (CDDP) resulted in severe side effects, including abscesses and significant nausea and vomiting.

The observed toxicities were greater than expected from either treatment alone, raising concerns about the safety of using this combination in routine clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concomitant radiation therapy and cis-diamminedichloroplatinum (II) in patients with advanced head and neck cancer. Creagan, ET., Fountain, KS., Frytak, S., et al.[2019]

In a phase III trial involving 237 patients with inoperable head and neck cancer, intra-arterial (IA) cisplatin did not show improved tumor control compared to intravenous (IV) cisplatin, despite a higher dose being administered via IA.

Patients receiving IV cisplatin experienced worse late dysphagia, indicating a potential safety concern with IV administration, while overall survival and locoregional control were similar between both treatment methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Late follow-up of the randomized radiation and concomitant high-dose intra-arterial or intravenous cisplatin (RADPLAT) trial for advanced head and neck cancer. Heukelom, J., Lopez-Yurda, M., Balm, AJ., et al.[2018]

The RADPLAT approach, which combines supradose intra-arterial cisplatin chemotherapy with radiotherapy, shows promising survival rates and high locoregional tumor control in patients with advanced head and neck squamous cell carcinoma.

This method not only demonstrates acceptable toxicity but also helps preserve organ function, addressing significant concerns associated with traditional surgical treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of advanced head and neck cancer with intra-arterial cisplatin and concurrent radiation therapy: the 'RADPLAT' protocol. Kumar, P., Robbins, KT.[2019]

In a study comparing cisplatin and cetuximab added to radiation therapy for head and neck squamous cell carcinoma, patients receiving cisplatin had a significantly higher 3-year disease-specific survival rate of 83% compared to 31% for those receiving cetuximab.

Cisplatin treatment was associated with a lower recurrence rate of disease (4 patients) compared to cetuximab (17 patients), indicating that cisplatin may be more effective in improving outcomes when combined with radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cisplatin versus cetuximab given concurrently with definitive radiation therapy for locally advanced head and neck squamous cell carcinoma. Ley, J., Mehan, P., Wildes, TM., et al.[2021]

Carboplatin-based chemoradiation therapy (CTRT) is a well-tolerated alternative for patients with locally advanced head and neck cancers who are unfit for cisplatin, with 84.1% of patients completing the planned treatment.

The study found a median overall survival of 28 months and progression-free survival of 17 months, suggesting that carboplatin-based CTRT may offer better outcomes compared to radical radiotherapy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin-based concurrent chemoradiation therapy in locally advanced head and neck cancer patients who are unfit for cisplatin therapy. Noronha, V., Sharma, V., Joshi, A., et al.[2018]

Citations

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Comparison of Weekly and Triweekly Cisplatin Regimens ... Overall, both schedules appear to be equally effective and safe. Our findings indicate that the treatment plan should be based on the individual ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2772906025000263

Review Article Comparing efficacy and safety of weekly vs. ... Both weekly and triweekly cisplatin regimens show comparable survival outcomes and safety profiles in patients with head and neck cancers, except for short term ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.6536

Cisplatin every three weeks versus ... High dose once every 3 weeks cisplatin (HDC; 100 mg/m 2 ) added to curative radiotherapy (RT) prolongs survival, but is associated with severe toxicities.

4. asco.org asco.org/abstracts-presentations/ABSTRACT379826

Six-year follow-up from the weekly-three-weekly study ... The estimated 5-year locoregional control rates were 48.2% and 55.2% in the once-a-week and once-every-3-weeks cisplatin arms respectively; absolute difference, ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05050162

NCT05050162 | Comparing Cisplatin Every Three Weeks ... This phase II/III trial compares whether cisplatin given weekly with radiation therapy is better tolerated than cisplatin given every three weeks with ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5599190/

A Systematic Review and Meta‐Analysis of Aggregate Data Three‐weekly high‐dose cisplatin (100 mg/m2) is considered the standard systemic regimen given concurrently with postoperative or definitive radiotherapy in ...

7. oncologyradiotherapy.com oncologyradiotherapy.com/articles/a-comparative-study-between-cisplatin-weekly-versus-every-3-weeks-concurrently-with-radiotherapy-in-the-locally-advanced-head-and--96415.html

A comparative study between cisplatin weekly versus every ... Thus, this study aimed at comparing high and low dose of cisplatin treatment concomitantly administered with radiation therapy regarding safety and efficacy in ...

8. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.999027/full

Efficacy and safety of weekly versus triweekly cisplatin ... Cisplatin-based regimens have been established as the most effective, and a dose of 100 mg/m2 given every 3 weeks is the most common (Tang et al., 2018).

9. nrgoncology.org nrgoncology.org/HN009

NRG-HN009: Cisplatin and Radiation for Advanced Head ... This study compares two schedules of the chemotherapy drug, cisplatin, given every three weeks versus every week with radiation for patients with this type of ...

10. insight.jci.org insight.jci.org/articles/view/196230

Lower, more frequent cisplatin dosing minimizes hearing ... Cisplatin-induced ototoxicity is dose dependent, often more severe with higher cumulative doses, and can significantly impact quality of life ...