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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how different doses of the chemotherapy drug cisplatin, combined with radiotherapy, affect head and neck cancer. Researchers aim to determine whether a high dose or a low dose of cisplatin is more effective for these cancers. The trial includes participants with specific types of head and neck cancer, such as those in the mouth or throat, who have not received cancer treatments in the past five years. Participants should be able to tolerate the treatments and plan to complete a full course of radiotherapy. As an unphased trial, this study provides patients the opportunity to contribute to important research that could enhance future cancer treatments.

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.

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 treat head and neck cancer, each with different safety profiles. High-dose cisplatin often causes significant side effects, with more than 75% of patients experiencing serious issues, especially with a three-week dosing schedule. Despite these challenges, the treatment remains effective.

In contrast, low-dose weekly cisplatin is less harmful, typically causing fewer severe side effects than the high-dose regimen. This makes it a popular choice for those concerned about the stronger effects of high-dose treatments.

While both treatments are effective, considering potential side effects and discussing them with a healthcare provider is important. ^{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 strategies of cisplatin combined with radiotherapy for head and neck cancer. Unlike the standard high-dose approach, the study is comparing both high-dose and low-dose regimens. The low-dose option, given weekly, could potentially reduce side effects and improve patient tolerance without compromising effectiveness. This investigation aims to find a more manageable and equally effective treatment option for patients, offering a new angle on how to balance efficacy with quality of life.

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

This trial will compare the effectiveness of high-dose versus low-dose cisplatin combined with radiotherapy for treating head and neck cancer. Research has shown that both high-dose and low-dose cisplatin, when paired with radiotherapy, effectively treat this cancer type. Participants in one arm of the trial will receive high-dose cisplatin, a common treatment that works well with radiotherapy, improving survival rates for patients with advanced cancer in this area. Participants in another arm will receive low-dose cisplatin, administered more frequently, which also leads to good survival outcomes and generally causes fewer side effects, such as less hearing loss, compared to high-dose treatments. Both options offer similar benefits, but low-dose cisplatin might be preferable for those concerned about side effects. ^{1 2 3 6 7}

Who Is on the Research Team?

Sara Kuruvilla, MD

Principal Investigator

London Health Sciences Centre, London Regional Cancer Program

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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).

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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 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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9875652/

Treatment outcomes of standard (high dose) cisplatin and non ... We demonstrated similar efficacy of lower dose weekly cisplatin and carboplatin/paclitaxel regimens and better safety profile of weekly cisplatin.

2. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2827612

Weekly Cisplatin Cycles and Outcomes for Chemoradiation ... There were 34 patients (24.0%) who received 5 cycles, 58 (40.8%) who received 6 cycles, and 50 (35.2%) who received 7 to 8 cycles (Table 1).

3. 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 ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10709267/

Treatment outcomes of radiotherapy with concurrent ... Tri-weekly cisplatin and radiotherapy (CDDP + RT) is a standard of care for locally advanced head and neck squamous cell carcinoma ...

5. thegreenjournal.com thegreenjournal.com/article/S0167-8140(24)00599-1/fulltext

Standard versus fractionated high-dose cisplatin plus ... Toxicity is remarkably reduced with the 4-day regimen compared to a standard cisplatin administration. •. The time-dependent outcomes remain ...

6. frontiersin.org frontiersin.org/journals/surgery/articles/10.3389/fsurg.2021.753049/full

Treatment Outcomes and the Safety of Chemoradiotherapy ... Conclusions: CRT with high-dose CDDP is safe and effective for the treatment of elderly patients with HNSCC. However, salvage treatments can be rarely conducted ...

7. ro-journal.biomedcentral.com ro-journal.biomedcentral.com/articles/10.1186/s13014-021-01966-4

safety propensity score analysis on 166 head and neck cancer ... Since three-weekly cisplatin (3w-CDDP) causes significant acute toxicity in more than three quarters of patients, many patients are likely to ...