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

(RADIO Trial)

Recruiting at 2 trial locations

Overseen By Sara Kuruvilla, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: London Health Sciences Centre OR Lawson Research Institute of St. Joseph's

Disqualifiers: Serious comorbidities, Prior head/neck cancer, Severe hearing loss, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

Duration: 6 weeks

100 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 drug cisplatin with radiotherapy for head and neck cancer?

Research shows that high-dose cisplatin combined with radiation therapy has been effective in treating locally advanced head and neck cancers, with some studies reporting improved survival times. Cisplatin, when used with radiation, has shown a survival benefit in these cancers, although the exact dose and schedule can vary. ^{1 2 3 4 5}

Is cisplatin with radiotherapy generally safe for humans?

Cisplatin, used alone or with radiotherapy, has been studied in various cancers and is generally considered safe, though it can cause side effects like nausea, vomiting, and temporary hearing issues. Kidney problems can occur, especially with high doses, so monitoring is important. ^{1 3 6 7 8}

How does the drug cisplatin with radiotherapy differ from other treatments for head and neck cancer?

This treatment is unique because it compares the effects of high-dose versus low-dose cisplatin, a chemotherapy drug, when used with radiotherapy for head and neck cancer. While cisplatin is commonly used, this study specifically examines the impact of different dosages on treatment outcomes, which is not typically addressed in standard treatment regimens. ^{1 3 4 5 9}

What is the purpose of this trial?

This study is a prospective open-label randomized clinical trial. Following informed consent eligible LASCCHN patients (n=100) planned for CRT will be stratified by tumor p16 status and then randomized in a 1:1 fashion to either concurrent HD cisplatin or concurrent weekly LD cisplatin.

Research Team

Sara Kuruvilla, MD

Principal Investigator

London Health Sciences Centre, London Regional Cancer Program

Eligibility Criteria

Adults with certain head and neck cancers, including oral squamous cell carcinoma, who are fit for high-dose cisplatin therapy. They must have good organ function, no severe hearing loss or neuropathy, not be pregnant or breastfeeding, able to attend treatments and follow-ups, and willing to use contraception.

Inclusion Criteria

My doctor plans for me to have intensive radiation therapy based on my health and cancer type.

My doctor thinks I can handle a strong chemotherapy drug based on my cancer type and health.

My blood counts and organ functions are within the required ranges.

Exclusion Criteria

I have had or will have chemotherapy before my main cancer treatment.

I have had radiation therapy on my head or neck before.

My cancer has spread to distant parts of my body.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either high-dose cisplatin on days 1, 22, and 43 or low-dose weekly cisplatin with concurrent radiotherapy

6 weeks

3 visits (in-person) for high-dose group, weekly visits for low-dose group

Follow-up

Participants are monitored for safety and effectiveness after treatment, including audiological examinations and quality of life assessments

1 year

Audiology testing at 3, 6, and 12 months post-treatment

Long-term Follow-up

Participants are monitored annually for progression-free survival and overall survival

Up to 5 years

Treatment Details

Interventions

• High-Dose Cisplatin
• Low-Dose Cisplatin
• Radiotherapy

Trial Overview The trial is testing two different doses of Cisplatin given alongside radiotherapy in patients with head and neck cancers. Participants will be randomly assigned to receive either a high dose once every three weeks (HD) or a low dose weekly (LD).

Participant Groups

Group I: ARM 1: High-Dose Cisplatin days 1, 22 & 43 with radiotherapy Active Control 2 Interventions

Group II: ARM 2: Low-Dose Cisplatin Q 1 wk + radiotherapy Active Control 2 Interventions

High-Dose 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
• Lung cancer
• Bladder cancer
• Squamous cell carcinoma of the head and neck

Approved in United States as Platinol for:

• Metastatic testicular tumors
• Metastatic ovarian tumors
• Advanced bladder cancer

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Lung cancer
• Bladder cancer

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Lung cancer
• Bladder cancer
• Squamous cell carcinoma of the head and neck

Who Is Running the Clinical Trial?

London Health Sciences Centre OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

668

Recruited

424,000+

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

678

Recruited

421,000+

London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

686

Recruited

427,000+

Lawson Health Research Institute

Lead Sponsor

Trials

684

Recruited

432,000+

Findings from Research

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 involving 129 patients with locally advanced epithelial malignancies, high-dose cisplatin (100 mg/m2) combined with radiation showed promising median survival times, particularly for squamous cell carcinoma of the head and neck, which had a median survival of 36 months.

The treatment was administered every 3 weeks during radiation therapy, and while median survival times for ovarian and lung cancers were 19 and 14 months respectively, some cancers like cervical carcinoma and prostate adenocarcinoma have not yet reached median survival, indicating ongoing effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with high-dose cisplatin and radiation for treatment of epithelial malignancies. Coughlin, CT.[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]

The addition of low-dose cisplatin (CDDP) to hyperfractionated radiation therapy (Hfx RT) significantly improved survival rates in patients with locally advanced squamous cell carcinoma of the head and neck, with 68% survival at 2 years compared to 49% with Hfx RT alone.

Despite the survival benefits, the combination treatment did not increase the incidence of severe radiation-induced toxicity compared to Hfx RT alone, although higher rates of hematologic toxicity were observed in patients receiving CDDP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperfractionated radiation therapy with or without concurrent low-dose daily cisplatin in locally advanced squamous cell carcinoma of the head and neck: a prospective randomized trial. Jeremic, B., Shibamoto, Y., Milicic, B., 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]

Cis-dichlorodiammineplatinum(II) (DDP) was found to be an effective treatment for 26 patients with advanced epidermoid carcinoma of the head and neck, showing complete and partial responses in several cases despite prior extensive treatments.

The treatment was generally safe, with manageable side effects such as mild myelosuppression and transient tinnitus, indicating that DDP can be used effectively even in heavily pretreated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CIS-Dichlorodiammineplatinum(II) in the treatment of epidermoid carcinoma of the head and neck. Wittes, RE., Cvitkovic, E., Shah, J., et al.[2013]

In a study of 82 advanced head and neck cancer patients undergoing concurrent chemoradiotherapy with high-dose cisplatin, 26% experienced renal impairment, highlighting the need for careful monitoring of kidney function during treatment.

Risk factors for cisplatin-induced renal impairment included the use of calcium channel blockers and lower hemoglobin levels, while the use of proton pump inhibitors was associated with a reduced risk, suggesting potential strategies to enhance patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of Risk Factors for High-dose Cisplatin-induced Renal Impairment in Head and Neck Cancer Patients. Koide, H., Noda, S., Okunuki, Y., et al.[2022]

In a Phase I study involving 40 patients with urologic and gynecologic cancers, cis-diamminedichloroplatinum(II) (CIS-DDP) was found to have manageable side effects, primarily nausea, vomiting, and anorexia, which resolved quickly after stopping the treatment.

The study indicated low levels of hematopoietic and renal toxicities, with no reported cases of hearing disturbances or tinnitus, suggesting a favorable safety profile for CIS-DDP at doses of 50 mg/m2 for single administration and 20 mg/m2/day for five consecutive days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Phase I study of a new antineoplastic agent, cis-diamminedichloroplatinum (II)]. [2013]

In a randomized trial involving 64 patients with advanced head and neck squamous carcinoma, both high-dose (120 mg/m2) and low-dose (60 mg/m2) cisplatin showed similar response rates of 16.1% and 17.8%, respectively.

The study found no significant difference in survival rates between the two dosage groups, indicating that increasing the dose of cisplatin did not enhance its effectiveness in treating this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose versus low-dose cisplatin in advanced head and neck squamous carcinoma: a randomized study. Veronesi, A., Zagonel, V., Tirelli, U., et al.[2017]

References

1. 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]

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

Clinical experience with high-dose cisplatin and radiation for treatment of epithelial malignancies. [2013]

3. England pubmed.ncbi.nlm.nih.gov

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

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

Hyperfractionated radiation therapy with or without concurrent low-dose daily cisplatin in locally advanced squamous cell carcinoma of the head and neck: a prospective randomized trial. [2022]

5. England pubmed.ncbi.nlm.nih.gov

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

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

CIS-Dichlorodiammineplatinum(II) in the treatment of epidermoid carcinoma of the head and neck. [2013]

7. Greece pubmed.ncbi.nlm.nih.gov

Analysis of Risk Factors for High-dose Cisplatin-induced Renal Impairment in Head and Neck Cancer Patients. [2022]

8. Japan pubmed.ncbi.nlm.nih.gov

[Phase I study of a new antineoplastic agent, cis-diamminedichloroplatinum (II)]. [2013]

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

High-dose versus low-dose cisplatin in advanced head and neck squamous carcinoma: a randomized study. [2017]