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

Recruiting in Palo Alto (17 mi)

+394 other locations

Overseen by Paul M Harari

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Recruiting

Sponsor: NRG Oncology

Disqualifiers: Oral cavity cancer, Metastatic disease, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This phase II/III trial compares whether cisplatin given weekly with radiation therapy is better tolerated than cisplatin given every three weeks with radiation therapy for the treatment of head and neck cancer that has spread to other places in the body (advanced). The second part of this study will also help to find out if the cisplatin given weekly approach will extend patients' life by at least the same amount of time as the cisplatin given every three weeks approach. Cisplatin is in a class of medications known as platinum-containing compounds that work by killing, stopping or slowing the growth of cancer cells. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Radiation with low-dose cisplatin given weekly may be effective in shrinking or stabilizing head and neck cancer or preventing its recurrence.

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.

What data supports the effectiveness of the drug cisplatin when used with radiation therapy for head and neck cancer?

Research shows that high-dose cisplatin combined with radiation therapy, known as the RADPLAT protocol, has promising survival results and helps preserve organ function in patients with advanced head and neck cancer. This approach has been shown to provide high tumor control rates with acceptable levels of side effects. ^{1 2 3 4 5}

Is high-dose or low-dose cisplatin with radiation safe for head and neck cancer treatment?

High-dose cisplatin with radiation can cause significant side effects, including severe nausea, vomiting, and other toxicities, which may limit its routine use. Some patients experience moderate toxicity with cisplatin as a single agent, and long-term follow-up shows ongoing concerns about toxicity. ^{2 4 6 7 8}

How does the high-dose vs low-dose cisplatin with radiation treatment for head and neck cancer differ from other treatments?

This treatment is unique because it compares different dosing schedules of cisplatin, a chemotherapy drug, combined with radiation therapy to determine the most effective and tolerable regimen for head and neck cancer. High-dose cisplatin is commonly used but can cause significant side effects, so this study explores whether lower doses might offer similar benefits with fewer side effects. ^{4 8 9 10 11}

Research Team

Paul M Harari

Principal Investigator

NRG Oncology

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Cisplatin (Alkylating agents)
• Radiation Therapy (Radiation)

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.

Participant Groups

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 Canada, Japan for the following indications:

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+

Stephanie Gaillard

NRG Oncology

Chief Medical Officer

MD from Johns Hopkins University

Norman Wolmark

NRG Oncology

Chief Executive Officer since 2023

MD from Harvard Medical School

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

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]

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 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 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]

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 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]

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]

References

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

Carboplatin-based concurrent chemoradiation therapy in locally advanced head and neck cancer patients who are unfit for cisplatin therapy. [2018]

2. United States 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. [2018]

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

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

4. United States 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). [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Cisplatin versus cetuximab given concurrently with definitive radiation therapy for locally advanced head and neck squamous cell carcinoma. [2021]

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

Concomitant radiation therapy and cis-diamminedichloroplatinum (II) in patients with advanced head and neck cancer. [2019]

7. England pubmed.ncbi.nlm.nih.gov

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

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

Concomitant weekly cisplatin and radiotherapy for head and neck cancer. [2022]

9. England pubmed.ncbi.nlm.nih.gov

In squamous cell head and neck cancer: which platinum, how much and how often? [2019]

10. India pubmed.ncbi.nlm.nih.gov

Comparison of acute toxicities of two chemotherapy schedules for head and neck cancers. [2022]

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

Postoperative reduced dose of cisplatin concomitant with radiation therapy in high- risk head and neck squamous cell carcinoma. [2013]