Cisplatin + Radiation for Head and Neck Cancer

Overseen By Susanne Arnold, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Susanne Arnold

Must be taking: Cisplatin

Must not be taking: Investigational agents

Disqualifiers: Pregnancy, Metastatic disease, Uncontrolled illness, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6-7 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore the effectiveness of cisplatin, a chemotherapy drug, when combined with radiation therapy for treating squamous cell carcinoma of the head and neck. Researchers seek to understand how cisplatin's side effects relate to the level of reactive oxygen species it produces, which are molecules that can damage cells. Participants will receive cisplatin doses either weekly or every three weeks, along with radiation. Suitable candidates are patients with head and neck cancer that has not spread to distant parts of the body and who have had or can tolerate full-dose radiation and chemotherapy. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are on investigational agents or have had recent chemotherapy or radiotherapy, you may need to stop those before joining the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both weekly and every-three-weeks schedules of the drug cisplatin, when combined with radiation, offer similar safety levels. Studies have found that these treatments for head and neck cancers yield comparable outcomes in terms of patient health and side effects.

In these studies, patients on either cisplatin schedule with radiation experienced similar side effects, suggesting that both options may be well-tolerated by patients with head and neck cancer. While all treatments can cause side effects, research indicates that these options are generally manageable and do not differ significantly in safety.

Discussing these findings with healthcare professionals is important to understand their personal implications. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Cisplatin combined with radiation (XRT) for head and neck cancer because it explores two different dosing schedules, potentially offering more flexibility and effectiveness. The "Every 3 Weeks" Cisplatin + XRT regimen allows for higher doses with longer recovery periods, which might improve tumor control and patient tolerance. Meanwhile, the "Weekly" Cisplatin + XRT option provides more consistent drug exposure, possibly enhancing treatment efficacy and reducing side effects. These variations could lead to better patient outcomes compared to the current standard of care, which often involves similar agents but with less optimized dosing strategies.

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

Research has shown that combining cisplatin with radiation effectively treats squamous cell carcinoma of the head and neck (SCCHN). In this trial, participants will receive radiation therapy with cisplatin, administered either weekly or every three weeks, to shrink or control these cancers. Patients who received a total dose of cisplatin during radiation therapy experienced significant survival benefits. This combination targets cancer cells more effectively than radiation alone, helping to prevent recurrence. While this trial compares both dosing schedules, each has shown promising results in improving outcomes for head and neck cancer patients. ^{3 6 7 8 9}

Who Is on the Research Team?

Susanne Arnold, MD

Principal Investigator

University of Kentucky

Are You a Good Fit for This Trial?

Adults with certain types of head and neck cancer (SCCHN) who haven't had chemotherapy for their current advanced cancer can join. They must be able to tolerate full treatment, have no distant metastases, and agree to use effective birth control. Those with significant hearing loss or other recent cancers (except specific cases in remission), uncontrolled illnesses, or pregnant/nursing women cannot participate.

Inclusion Criteria

I agree to use effective birth control methods.

I had head or neck cancer before and can handle the full dose of radiation and chemotherapy.

I have not received chemotherapy for my advanced head or neck cancer.

Exclusion Criteria

I am HIV-positive with uncontrolled HIV.

I recently underwent chemotherapy or radiotherapy.

My cancer has spread from its original location.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive concurrent radiation therapy and cisplatin, either weekly or every 3 weeks, for 6-7 weeks

6-7 weeks

Weekly visits for radiation and cisplatin administration

Follow-up

Participants are monitored for toxicity and progression-free survival for 2 years after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• XRT

Trial Overview The trial is testing the effectiveness of standard radiation therapy combined with cisplatin given either weekly or every three weeks on SCCHN. It also examines how the drug's toxicity relates to oxidative stress markers produced during treatment.

How Is the Trial Designed?

Group I: Weekly Cisplatin + XRT Experimental Treatment 2 Interventions

Weekly Cisplatin + XRT

Group II: Every 3 Weeks Cisplatin + XRT Experimental Treatment 2 Interventions

Every 3 Weeks Cisplatin + XRT

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

Who Is Running the Clinical Trial?

Susanne Arnold

Lead Sponsor

Trials

11

Recruited

1,300+

Published Research Related to This Trial

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 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]

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 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 of 35 patients with advanced squamous cell carcinoma of the head and neck, the combination of cis-platinum (CDDP) and radiotherapy (RT) resulted in a high complete response rate of 75%, with an overall response rate of 100%.

The treatment was well tolerated, with gastrointestinal and hematologic toxicities being the most common side effects, making CDDP plus RT a safe and effective option, especially for patients with good performance status and unresectable stage II or III disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simultaneous cis-platinum and radiotherapy in inoperable or locally advanced squamous cell carcinoma of the head and neck. Gasparini, G., Pozza, F., Recher, G., et al.[2018]

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]

Combined modality treatment using cisplatin and radiotherapy for head and neck cancer shows promising results in local control and survival rates, leading to the initiation of three Phase III trials for advanced stages of various cancers in this region.

While the combination treatment can increase mucosal toxicity and myelosuppression, it does not hinder the delivery of standard radiotherapy, suggesting that patient compliance can be managed effectively during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cisplatin and radiotherapy in the management of locally advanced head and neck cancer. Forastiere, AA.[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]

In a study of 41 patients with advanced oral squamous cell carcinoma, a preoperative treatment combining cisplatin or carboplatin with irradiation resulted in a high overall response rate of 97.6%, with 61% achieving a complete response.

The treatment was well tolerated, with low and reversible side effects, and led to a promising 5-year survival rate of 81.5%, indicating its effectiveness even in advanced stages of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative simultaneous cisplatin- or carboplatin-based chemotherapy and radiotherapy for squamous cell carcinoma of the oral cavity. Kirita, T., Ohgi, K., Tsuyuki, M., et al.[2013]

In a study of 72 patients with advanced head and neck cancer receiving concurrent chemoradiotherapy with generic cisplatin, treatment completion rates were high, indicating good tolerability of the drug.

The incidence of severe adverse events was relatively low, with only 14% experiencing grade 3/4 leukopenia and no severe kidney issues reported, suggesting that generic cisplatin is a safe option for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemoradiotherapy With Generic Cisplatin Formulations for Head and Neck Cancers. Shimada, R., Tsukahara, K., Takase, S., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05050162

NCT05050162 | Comparing Cisplatin Every Three Weeks ... Radiation with low-dose cisplatin given weekly may be effective in shrinking or stabilizing head and neck cancer or preventing its recurrence. Detailed ...

2. medicaljournalssweden.se medicaljournalssweden.se/actaoncologica/article/download/26800/31530/79417

Cisplatin and Radiotherapy in the Treatment of Locally ... Radiotherapy alone has an impact on the short-term prognosis of advanced head and neck cancer but the long-term benefits have been moderate (2, 3). The majority ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9197353/

Weekly Cisplatin Plus Radiation for Postoperative Head ... Cumulative cisplatin dose during radiation therapy (RT) for SCCHN has a significant correlation with survival, with 200 mg/m2 suggested to be ...

4. oncologyradiotherapy.com oncologyradiotherapy.com/articles/a-comparative-study-between-cisplatin-weekly-versus-every-3-weeks-concurrently-with-radiotherapy-in-the-locally-advanced-head-and--96415.html

A comparative study between cisplatin weekly versus every ... Thus, this study aimed at comparing high and low dose of cisplatin treatment concomitantly administered with radiation therapy regarding safety and efficacy in ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0168365925005437

Effective head and neck cancer treatment combines ... The data indicate that, despite significant molecular variations and responses, the RT + 1 %- cisplatin in PSARA therapy had promising outcomes ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4873705/

Long term results of comparison of concurrent low-dose ... Daily cisplatin group appears to be comparable to weekly schedule in terms of survival outcomes, compliance and toxicity.

7. 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 ...

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

Treatment outcomes of radiotherapy with concurrent ... Treatment outcomes of radiotherapy with concurrent weekly cisplatin in older patients with locally advanced head and neck squamous cell ...

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.21.01293

Weekly Cisplatin Plus Radiation for Postoperative Head ... Chemoradiotherapy with weekly cisplatin is noninferior to 3-weekly cisplatin for patients with postoperative high-risk LA-SCCHN.