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}

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 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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

IHA Hematology Oncology Consultants-Ann Arbor Ypsilanti, MI

UCSF Medical Center-Mount Zion San Francisco, CA

Kaiser Permanente-Lone Tree Lone Tree, CO

Langlade Hospital and Cancer Center Antigo, WI

More Trial Locations

Who Is Running the Clinical Trial?

NRG Oncology Lead Sponsor

National Cancer Institute (NCI) Collaborator

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] Cisplatin-based chemoradiation (CTRT) is the standard of care in locally advanced head and neck cancers. Limited treatment options are available in patients unfit for cisplatin.

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] The radiation and concomitant high-dose intra-arterial or intravenous cisplatin (RADPLAT) phase III trial compared intra-arterial (IA) to intravenous (IV) cisplatin-based chemoradiation for head and neck cancer. Long-term efficacy and toxicity are reported after a median follow-up of 7.5 years.

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] The prognosis for patients presenting with advanced head and neck squamous cell carcinoma using "standard" treatment approaches, such as surgery followed by radiotherapy or radiotherapy alone, remains poor. Additionally, patients often lose their voice or swallowing ability when a primary surgical approach is used. Although systemic chemotherapy, when combined concurrently with radiotherapy, appears to be superior to radiation alone, the use of neoadjuvant or adjuvant systemic chemotherapy has not improved survival when combined with either surgery or radiotherapy. Even with the use of concurrent systemic chemotherapy and radiotherapy, the majority of the patients still succumb to their disease, usually failing locoregionally. Among the newer strategies being explored is the use of supradose intra-arterial chemotherapy (ie, cisplatin) with current radiotherapy. Acronymed "RADPLAT," this novel therapeutic approach delivers supradoses of weekly cisplatin chemotherapy with concurrent radiotherapy with acceptable toxicity, high locoregional tumor control rates, and very promising survival results. In addition, the RADPLAT approach allows for the preservation of organ function. This article reviews the evolution of the RADPLAT concept from a phase I trial to a recently completed Radiation Therapy Oncology Group trial confirming its feasibility in a multi-institutional setting.

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] High-dose cisplatin (Cis) is a preferred systemic agent for concurrent chemoradiation (CRT) in locally advanced head and neck squamous cell cancer (LAHNSCC) patients. As some patients are unable to tolerate Cis, this study compares the toxicity and efficacy of weekly cisplatin-paclitaxel (CP) regimen with Cis.

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] Whether or not cisplatin and cetuximab are similarly effective in improving outcomes when added to radiation therapy (RT) in squamous cell carcinoma of the head and neck is unknown.

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

Concomitant radiation therapy and cis-diamminedichloroplatinum (II) in patients with advanced head and neck cancer. [2019] Three patients with locally advanced head and neck squamous cell cancer received concomitant radiation therapy (XRT) and cis-diamminedichloroplatinum (CDDP). The dose of 6,000 rads was to be administered in two 3,000-rad courses separated by 3 weeks. The CDDP, 30 mg/m2, was to be given intravenously on days 2 and 12 of each half of XRT. We were especially concerned with the occurrence of an abscess in one patient and an abscess with hemorrhage in another. In addition, each patient experienced severe and intractable nausea, vomiting, and a pervasive feeling of ill-health which seemed out of proportion to that usually observed from either XRT or CDDP alone. If the findings in this pilot study are confirmed, the toxicity of XRT with concurrent CDDP as used in our study may well obviate routine clinical usage.

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] Seventeen patients with head and neck squamous cell carcinoma were treated with cis-diamminedichloroplatinum (II) CDDP 2.5 mg./kg. I.V. as a single agent. One complete and five partial responses were observed with only moderate toxicity.

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

Concomitant weekly cisplatin and radiotherapy for head and neck cancer. [2022] The most common chemoradiotherapy regimen is high-dose (100 mg/m(2)) three-weekly cisplatin with concomitant radiotherapy; however, this protocol is associated with acute and late toxicities. Here, we reviewed the dose intensity and toxicity for concomitant weekly cisplatin and radiotherapy in patients with head and neck cancer.

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

In squamous cell head and neck cancer: which platinum, how much and how often? [2019] Head and neck squamous cell carcinoma is the fifth most common cancer worldwide. Patients who present with locally advanced disease are usually treated with a combined modality approach, often including chemotherapy, and frequently using the platinum agents cisplatin or carboplatin. In locally advanced head and neck squamous cell carcinoma, carboplatin and cisplatin have both been found to produce a survival benefit when added to radiation therapy. Although it appears that cisplatin may be more active, carboplatin is better tolerated. Cisplatin has been given concurrently with radiation every 3 weeks, weekly or daily. There have been no prospective trials comparing the different cisplatin dose schedules, but a dose of 100 mg/m(2) administered every 3 weeks on days 1, 22 and 43 with concurrent standard fractionation radiation therapy is the most widely used and tested regimen. The required total dose of cisplatin is also not known, although a necessary dose threshold of 200 mg/m(2) has been suggested.

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

Comparison of acute toxicities of two chemotherapy schedules for head and neck cancers. [2022] Chemo-radiotherapy has become the standard of care for loco-regionally advanced head and neck cancers. Platinum based regimens are the most effective. Although benefits are proven with chemo-radiation, acute toxicities are markedly increased. The dose and delivery schedules of Cisplatin have ranged from intermittent higher dose [100 mg/m2] every 3 weeks to low dose [6 mg/m2] daily administration. At present there is no data indicating which regimen is superior.

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] The role of low doses of cisplatin and concomitant postoperative radiotherapy in high risk head and neck squamous cell carcinoma has not yet been defined.