High-Dose vs Low-Dose Cisplatin with Radiation for Head and Neck Cancer
Palo Alto (17 mi)Overseen byPaul M Harari
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2 & 3
Recruiting
Sponsor: NRG Oncology
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?This phase II/III trial compares the effect of the combination of high-dose cisplatin every three weeks and radiation therapy versus low-dose cisplatin weekly and radiation therapy for the treatment of patients with locoregionally advanced head and neck cancer. Chemotherapy drugs, 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. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. This study is being done to find out if low-dose cisplatin given weekly together with radiation therapy is the same or better than high-dose cisplatin given every 3 weeks together with radiation therapy in treating patients with head and neck cancer.
What safety data is available for high-dose vs low-dose cisplatin with radiation in head and neck cancer treatment?The safety data for high-dose vs low-dose cisplatin with radiation in head and neck cancer treatment includes several studies. High-dose cisplatin is commonly used but is associated with significant acute and late toxicities. A study comparing high-dose cisplatin with a weekly cisplatin-paclitaxel regimen found differences in toxicity profiles. Another study reported severe nausea, vomiting, and other toxicities when using cisplatin with radiation, suggesting potential limitations in routine clinical use. The RADPLAT trial provided long-term toxicity data, comparing intra-arterial and intravenous cisplatin delivery methods. Overall, while cisplatin is effective, its use is limited by its toxicity, and alternative dosing schedules or combinations may offer different safety profiles.127911
Is the drug Cisplatin with Radiation Therapy a promising treatment for head and neck cancer?Yes, Cisplatin combined with Radiation Therapy is considered a promising treatment for head and neck cancer. It has been shown to improve survival rates when used together, and Cisplatin is often preferred for its effectiveness in treating this type of cancer.567811
What data supports the idea that High-Dose vs Low-Dose Cisplatin with Radiation for Head and Neck Cancer is an effective treatment?The available research shows that using high-dose cisplatin with radiation, known as the RADPLAT protocol, is effective for treating advanced head and neck cancer. This approach has shown high rates of controlling the tumor in the area where it started and promising survival results. It also helps preserve important functions like speaking and swallowing, which can be lost with surgery. Compared to other treatments, high-dose cisplatin with radiation offers better outcomes for patients who can tolerate it.3491011
Do I need to stop my current medications for this trial?The trial protocol does not specify whether you need to stop taking your current medications. However, if you have a history of hypersensitivity to cisplatin or platinum-containing compounds, you may not be eligible. It's best to discuss your current medications with the trial team.
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
I am fully active or restricted in physically strenuous activity but can do light work.
I have had a PET/CT scan of my neck with contrast.
My throat cancer is p16-negative and matches specific stage criteria.
I am not pregnant and have not had menopause or been sterilized.
I have had a CT scan of my neck with contrast, unless it was not suitable for me.
My cancer's origin is unknown, I may or may not smoke, and it has spread to nearby lymph nodes.
My kidney function, measured by creatinine clearance, is good.
I have had a recent high-quality scan of my neck.
My cancer is in the oropharynx, I've smoked 10 or fewer pack-years, and my cancer stage fits specific criteria.
My cancer shows high levels of p16 according to my pathology report.
My cancer has not spread to distant parts of my body according to the latest tests.
My cancer is in the oropharynx, I've smoked more than 10 pack-years, and my cancer stage fits specific criteria.
I am 18 years old or older.
I have had an MRI of the neck with contrast, unless it was not recommended for me.
My cancer is in the larynx/hypopharynx and matches specific stage criteria.
Exclusion Criteria
I am not pregnant or nursing, or I am willing to stop nursing.
I have a kidney condition that could worsen with cisplatin therapy.
My cancer has come back after treatment.
I do not have an infection that needs IV antibiotics right now.
I have cancer in my mouth, nasopharynx, or a p16-negative unknown primary cancer.
My cancer has spread to distant parts of my body.
I've had radiation in the same area where my current cancer is located.
I haven't been hospitalized for unstable angina in the last 6 months.
I have not had a heart attack in the last 6 months.
I have severe, unfixable electrolyte issues despite treatment.
I do not have severe numbness or pain in my hands or feet.
Treatment Details
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.
4Treatment groups
Experimental Treatment
Group I: Arm IV (low-dose cisplatin, radiation therapy)Experimental Treatment4 Interventions
p16-POSITIVE OPC/CUP: 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 low-dose cisplatin IV QW during radiation therapy in the absence of disease progression or unacceptable toxicity.
Group II: Arm III (high-dose cisplatin, radiation therapy)Experimental Treatment4 Interventions
p16-POSITIVE OPC/CUP: 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 high-dose cisplatin IV Q3W (on days 1, 22, and 43) during radiation therapy in the absence of disease progression or unacceptable toxicity.
Group III: Arm II (low-dose cisplatin, radiation therapy)Experimental Treatment4 Interventions
NON-OPC/p16-NEGATIVE OPC: 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 low-dose cisplatin IV QW during radiation therapy in the absence of disease progression or unacceptable toxicity.
Group IV: ARM I (high-dose cisplatin, radiation therapy)Experimental Treatment4 Interventions
NON-OPC/p16-NEGATIVE OPC: 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 high-dose cisplatin IV Q3W (on days 1, 22, and 43) during radiation therapy in the absence of disease progression or unacceptable toxicity.
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 nearbySelect from list below to view details:
IHA Hematology Oncology Consultants-Ann ArborYpsilanti, MI
UCSF Medical Center-Mount ZionSan Francisco, CA
Kaiser Permanente-Lone TreeLone Tree, CO
Langlade Hospital and Cancer CenterAntigo, WI
More Trial Locations
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Who is running the clinical trial?
NRG OncologyLead Sponsor
National Cancer Institute (NCI)Collaborator
References
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.
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.
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.
Phase II trial of a simultaneous radiochemotherapy with cisplatinum and paclitaxel in combination with hyperfractionated-accelerated radiotherapy in locally advanced head and neck tumors. [2022]Simultaneous radiochemotherapy (RCT) is the treatment of choice for locally advanced head and neck cancers. In order to evaluate the toxicity and the survival rates, we investigated the use of a very aggressive combination protocol that included cisplatinum and paclitaxel combined with hyperfractionated-accelerated radiotherapy. The final results of the phase II study are listed below.
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.
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.
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.
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.
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.
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.
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.