Cisplatin for Oropharyngeal Cancer

Recruiting at 3 trial locations

Overseen By Clinical Trial Navigator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Zachary Zumsteg

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: Distant metastasis, Recurrent disease, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 5-6 weeks

50 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

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 for treating oropharyngeal cancer?

Cisplatin is a key part of chemotherapy for oropharyngeal cancer, and studies show it can lead to complete or partial responses in patients with head and neck cancers, including oropharyngeal cancer. It is often used in combination with other treatments to improve survival rates, especially in HPV-positive cases. ^{1 2 3 4 5}

Is cisplatin safe for treating oropharyngeal cancer?

Cisplatin, used in various forms for head and neck cancers, has shown moderate to mild side effects like low white blood cell counts, anemia, and nausea, but is generally well-tolerated. Serious side effects like kidney issues were rare, and most patients could complete their treatment. ^{3 5 6 7 8}

What makes the drug cisplatin unique for treating oropharyngeal cancer?

Cisplatin is unique for treating oropharyngeal cancer because it is a key component of systemic chemotherapy and has a high tumor response rate, especially when used in high doses. It is often used in combination with radiation therapy, and its effectiveness is closely related to the dosage, although the ideal dosing regimen is still being studied. ^{3 5 9 10 11}

What is the purpose of this trial?

This is a single institution phase II study that will enroll patients with T0-3N0-2 p16-positive oropharyngeal squamous cell carcinoma (OSCC) undergoing resection of all gross visible disease at the primary site and in the lymph nodes.

Research Team

Zachary S. Zumsteg

Principal Investigator

Cedars-Sinai Medical Center

Eligibility Criteria

This trial is for individuals with p16-positive oropharyngeal squamous cell carcinoma (OSCC) who have had surgery to remove all visible cancer from the throat and lymph nodes. Details on eligibility criteria are not fully provided.

Inclusion Criteria

I have had or will have surgery to remove lymph nodes in my neck.

I will have or had surgery to remove all visible cancer in my head or neck.

My cancer is linked to HPV or shows a strong p16 presence.

Exclusion Criteria

Pregnant or breast-feeding women

My cancer has spread to other parts of my body.

It has been more than 56 days since my surgery to remove the cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery

Participants undergo transoral robotic surgery for resection of all gross visible disease at the primary site and in the lymph nodes

1 week

Treatment

Participants receive a de-intensified cisplatin-based chemoradiation regimen, with radiation therapy and weekly cisplatin doses

5-6 weeks

Weekly visits for cisplatin administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

• Cisplatin

Trial Overview The study is testing how well Cisplatin, a chemotherapy drug, works in treating HPV-associated throat cancer after surgery. It's a phase II trial at one medical institution.

Participant Groups

Group I: Single Arm Experimental Treatment 1 Intervention

Low risk pathology with post-op HPV DNA (-): cisplatin-based chemoradiation with 30 Gy in 15 fractions and 3 cycles of weekly cisplatin 40mg/m2 IV on Days 1, 8, and 15 of radiation. Low risk pathology with post-op HPV DNA (+): cisplatin-based chemoradiation with 40 Gy in 20 fractions and 4 cycles of weekly cisplatin 40mg/m2 IV on Days 1, 8, 15, and 22 of radiation. High risk pathology with post-op HPV DNA (-), excluding patients with both 5 LN+ and ENE+ or pre-op HPV DNA≤12 copies/mL: cisplatin-based radiation with 40 Gy in 20 fractions and 4 cycles of weekly cisplatin 40mg/m2 IV on Days 1, 8, 15, and 22 of radiation. High risk pathology with post-op HPV DNA (+) OR pre-op HPV DNA≤12 copies/mL OR both 5 or more LN+ and ENE+: cisplatin-based radiation with 50 Gy in 25 fractions with 5 cycles of weekly cisplatin 40mg/m2 IV on Days 1, 8, 15, 22, and 29 of radiation.

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?

Zachary Zumsteg

Lead Sponsor

Trials

1

Recruited

50+

Findings from Research

In a study of 421 patients with HPV-associated oropharyngeal squamous cell carcinoma, high-dose cisplatin (HDC) showed better outcomes for stage III disease, including lower rates of locoregional recurrence and distant metastasis, as well as improved overall survival compared to triweekly carboplatin (TC).

However, HDC was associated with significantly higher toxicity, including increased rates of severe leukopenia and weight loss, suggesting that TC may be a safer option for patients with early-stage disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Triweekly carboplatin as a potential de-intensification agent in concurrent chemoradiation for early-stage HPV-associated oropharyngeal cancer. Iganej, S., Beard, BW., Chen, J., et al.[2020]

Patients with HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) and nonsmokers showed better overall and disease-free survival, regardless of whether they received high dose (HD) or low dose (LD) cisplatin, indicating the importance of tumor characteristics in treatment outcomes.

A cumulative cisplatin dose of ≥200 mg/m2 was linked to a lower rate of distant metastasis, with the HD regimen allowing more patients to reach this dose while maintaining a similar toxicity profile to the LD regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deployment of cisplatin in Veterans with oropharyngeal cancer: toxicity and impact on oncologic outcomes. Soliman, O., Wilde, DC., Kemnade, JO., et al.[2023]

In a study of 253 patients with locally advanced oropharyngeal cancer, both carboplatin-5-fluorouracil and high-dose cisplatin regimens showed similar efficacy in terms of overall survival, disease-free survival, and locoregional control rates after 3 years.

The 3-year overall survival rates were 79.1% for carboplatin-5FU and 74.9% for cisplatin, indicating that both chemotherapy regimens are effective options for treatment, with no significant differences found between them.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent chemoradiation with carboplatin-5-fluorouracil versus cisplatin in locally advanced oropharyngeal cancers: is more always better? Barkati, M., Fortin, B., Soulières, D., 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 phase I/II study involving 13 patients with high-risk head and neck squamous cell carcinoma, weekly cisplatin (30 mg/m2) was found to be a safe and tolerable regimen for postoperative chemoradiotherapy, with a high compliance rate of 85%.

The most common acute adverse events were mild, including grade 1-2 anemia (50%), mucositis (43%), and nausea/vomiting (43%), indicating that the treatment was manageable with minimal severe side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Postoperative chemoradiotherapy with weekly cisplatin for patients at high-risk for recurrence of head and neck squamous cell carcinoma-A phase I/II study]. Hanai, N., Suzuki, A., Ozawa, T., et al.[2013]

In a phase I-II study involving 12 patients with unresectable head and neck squamous cell carcinomas, the combination of radiation and cisplatin (CDDP) resulted in a complete response in 66% of patients, with some remaining disease-free for up to 34 months after treatment.

The recommended dose of CDDP was determined to be 6 mg/m2/day, with manageable side effects; notably, mucositis severity was similar to that of radiation alone, and there was no significant nephro-, oto-, or neurotoxicity observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy with concomitant continuous cisplatin infusion for unresectable tumors of the upper aerodigestive tract: results of a phase I study. Bachaud, JM., Chatelut, E., Canal, P., et al.[2019]

In a study of 21 patients with advanced oropharyngeal carcinoma, selective intraarterial chemoradiation therapy using high-dose cisplatin (300 mg/m²) resulted in a 2-year overall survival rate of 71.3% for those who completed the treatment.

The therapy also achieved a high locoregional control rate of 95.0% and a disease-free survival rate of 67.7%, indicating its efficacy while potentially reducing the number of treatment procedures compared to traditional methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective intraarterial chemoradiation therapy for oropharyngeal carcinoma with high-dose cisplatin. Nishio, R., Saito, K., Ito, H., et al.[2021]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Impact of cisplatin dose and smoking pack-years in human papillomavirus-positive oropharyngeal squamous cell carcinoma treated with chemoradiotherapy. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Triweekly carboplatin as a potential de-intensification agent in concurrent chemoradiation for early-stage HPV-associated oropharyngeal cancer. [2020]

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

Deployment of cisplatin in Veterans with oropharyngeal cancer: toxicity and impact on oncologic outcomes. [2023]

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

Concurrent chemoradiation with carboplatin-5-fluorouracil versus cisplatin in locally advanced oropharyngeal cancers: is more always better? [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. Japan pubmed.ncbi.nlm.nih.gov

[Postoperative chemoradiotherapy with weekly cisplatin for patients at high-risk for recurrence of head and neck squamous cell carcinoma-A phase I/II study]. [2013]

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

Radiotherapy with concomitant continuous cisplatin infusion for unresectable tumors of the upper aerodigestive tract: results of a phase I study. [2019]

9. Japan pubmed.ncbi.nlm.nih.gov

Selective intraarterial chemoradiation therapy for oropharyngeal carcinoma with high-dose cisplatin. [2021]

10. 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]

11. 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]