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

80 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial involves treating patients with advanced head and neck cancer using a combination of radiation and the chemotherapy drug cisplatin. The goal is to see how effective this treatment is and how it affects patients. Different dosing schedules of cisplatin during radiation are being explored for efficacy and toxicity.

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.

What data supports the effectiveness of the drug Cisplatin when used with radiation for head and neck cancer?

Research shows that using Cisplatin with radiation can improve tumor control and survival in advanced head and neck cancer, with some studies reporting positive responses in patients. ^{1 2 3 4 5}

Is the combination of Cisplatin and Radiation safe for treating head and neck cancer?

The combination of Cisplatin (also known as Platinol, Cisplatinum, and other names) and Radiation is generally considered safe for treating head and neck cancer, though it can cause side effects like nausea, vomiting, and blood-related issues. Some studies reported severe side effects, but overall, the treatment is well tolerated with careful monitoring. ^{5 6 7 8 9}

How is the drug Cisplatin + Radiation unique for treating head and neck cancer?

Cisplatin combined with radiation therapy is unique because it enhances the effects of radiation in treating locally advanced head and neck cancer, with a common regimen being 100 mg/m² of cisplatin every 3 weeks. While cisplatin is more active than carboplatin, it is also associated with higher toxicity, making it a potent but challenging option for patients. ^{1 3 10 11 12}

Research Team

Susanne Arnold, MD

Principal Investigator

University of Kentucky

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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 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]

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 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 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 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]

References

1. 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]

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

Cisplatin and radiotherapy in the management of locally advanced head and neck cancer. [2019]

3. 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]

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

Preoperative simultaneous cisplatin- or carboplatin-based chemotherapy and radiotherapy for squamous cell carcinoma of the oral cavity. [2013]

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

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

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

Chemoradiotherapy With Generic Cisplatin Formulations for Head and Neck Cancers. [2020]

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

Concomitant radiation therapy and cis-diamminedichloroplatinum (II) in patients with advanced head and neck cancer. [2019]

8. Greece pubmed.ncbi.nlm.nih.gov

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

9. Switzerland pubmed.ncbi.nlm.nih.gov

Simultaneous cis-platinum and radiotherapy in inoperable or locally advanced squamous cell carcinoma of the head and neck. [2018]

10. England pubmed.ncbi.nlm.nih.gov

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

11. India pubmed.ncbi.nlm.nih.gov

Phase IIb trial comparing two concurrent cisplatin schedules in locally advanced head and neck cancer. [2020]

12. France pubmed.ncbi.nlm.nih.gov

[Concomitant association of radiotherapy and chemotherapy (CDDP 4-6 mg/m2/daily in continuous i.v. administration) in locally advanced ORL tumors]. [2009]