Chemoradiation for Oropharyngeal Cancer

Recruiting at 3 trial locations

Overseen By Amy Oppenheim

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Cedars-Sinai Medical Center

Must not be taking: 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

Compensation: Varies

Number of Visits: Unknown

Duration: 3-5 weeks

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will enroll patients with HPV-associated oropharyngeal cancer, undergoing resection of all gross visible disease at the primary site and in the lymph nodes. A total of 40 patients who have had or will require surgery to remove cancer cells prior to starting chemoradiation may be enrolled. All eligible patients will receive de-intensified cisplatin-based chemoradiation, with high-risk patients receiving a higher dose and longer treatment period than other patients on the study. The study will assess whether a de-intensified version of standard chemoradiation treatment will be just as effective in treating HPV-associated oropharyngeal cancer while causing less side effects than standard dosing.

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you have severe co-morbidities or are taking medications that could interfere with the trial, you should discuss this with the trial team.

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 idea that Chemoradiation for Oropharyngeal Cancer is an effective treatment?

The available research shows that using cisplatin with radiation therapy is effective for treating oropharyngeal cancer. In one study, 66% of patients had a complete response, meaning their cancer was no longer detectable after treatment. Another study found that 72% of primary tumors had a complete response, and all patients with neck lymph node involvement responded completely. These results suggest that combining cisplatin with radiation can significantly reduce or eliminate tumors in many patients. ^{1 2 3 4 5}

What data supports the effectiveness of the drug cisplatin when used with radiation therapy for oropharyngeal cancer?

Research shows that combining cisplatin with radiation therapy can lead to significant tumor reduction in head and neck cancers, including oropharyngeal cancer. In one study, 66% of patients had a complete response, meaning their tumors disappeared, and some remained disease-free for over a year after treatment. ^{1 2 3 4 5}

What safety data exists for chemoradiation treatment with cisplatin for oropharyngeal cancer?

Several studies provide safety data for cisplatin-based chemoradiation in head and neck cancers, including oropharyngeal cancer. One study with 72 patients using generic cisplatin reported grade 3/4 leukopenia in 14%, neutropenia in 12%, and hypochromia in 5% of cases, with no severe renal toxicity. Another phase I study found dose-limiting toxicities at 7 mg/m2/day, including neutropenia and thrombocytopenia, but no nephro-, oto-, or neurotoxicity. A recommended dose was 6 mg/m2/day. A separate analysis highlighted renal impairment as a concern with high-dose cisplatin, necessitating dose adjustments. Long-term follow-up from the RADPLAT trial reported on the efficacy and toxicity of high-dose cisplatin delivered intra-arterially or intravenously. ^{1 2 6 7 8}

Is chemoradiation with cisplatin safe for treating oropharyngeal cancer?

Studies show that chemoradiation using cisplatin is generally well tolerated, but it can cause side effects like low white blood cell counts (leukopenia), low neutrophil counts (neutropenia), and low red blood cell counts (hypochromia). Some patients may also experience mild kidney issues, but severe kidney problems are rare. ^{1 2 6 7 8}

Is the drug Cisplatin a promising treatment for oropharyngeal cancer?

Yes, Cisplatin is a promising drug for treating oropharyngeal cancer. Studies show that when used with radiation, it can lead to a complete response in many patients, meaning the cancer is no longer detectable. It is considered effective in improving outcomes for patients with advanced stages of this cancer. ^{1 2 4 5 9}

What makes the chemoradiation treatment with cisplatin unique for oropharyngeal cancer?

This treatment is unique because it combines radiation therapy with a continuous infusion of cisplatin, which is a chemotherapy drug, to enhance the effectiveness against advanced oropharyngeal cancer. The continuous infusion method aims to maintain a steady level of the drug in the body, potentially improving outcomes compared to other dosing schedules. ^{1 2 4 5 9}

Research Team

Zachary S. Zumsteg

Principal Investigator

Cedars-Sinai Medical Center

Eligibility Criteria

Adults with HPV-positive oropharyngeal cancer who've had surgery to remove the cancer can join this trial. They must be in good health, not pregnant, and have no recent other cancers or severe illnesses. People with very advanced disease, distant spread of cancer, inability to completely remove the tumor surgically, significant heart issues within the last 6 months, uncontrolled infections or AIDS cannot participate.

Inclusion Criteria

My surgery showed I have advanced cancer features.

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

My cancer started with an unknown primary but has spread to at least one lymph node in my neck.

Exclusion Criteria

I haven't had any serious cancer except for some types in the last 2 years.

Severe, active co-morbidity, defined as follows: Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months, Transmural myocardial infarction within the last 6 months, Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration, Hepatic insufficiency resulting in clinical jaundice and/or known coagulation defects, Uncontrolled Acquired Immune Deficiency Syndrome (AIDS), defined as a CD4 count < 200 at screening or an AIDS-defining opportunistic infection within the last 6 months, Moderate to severe hearing loss, Active connective tissue disease (e.g. systemic lupus erythematous, scleroderma) requiring immunosuppression, Pregnant or breast-feeding women, Prior allergic reaction to cisplatin, Live vaccines within 30 days prior to the first dose of chemoradiation. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, BCG, and typhoid (oral vaccine). Season influenza vaccines for injection are generally killed virus vaccines and are allowed; however intranasal influenza vaccines (e.g. Flu-Mist®) are live attenuated vaccines and are not allowed.

I have received radiation treatment to my head or neck area above 30 Gy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery

Participants undergo trans-oral robotic surgery (TORS) to remove all gross visible disease at the primary site and in the lymph nodes

1-2 weeks

Treatment

Participants receive de-intensified cisplatin-based chemoradiation, with high-risk patients receiving a higher dose and longer treatment period

3-5 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

• Cisplatin
• Cisplatin-based Radiation Therapy

Trial Overview The study is testing a less intense version of chemoradiation therapy using cisplatin after robotic surgery for HPV-related throat cancer. It aims to see if lower doses are as effective but cause fewer side effects than standard treatment. High-risk patients will receive more intensive treatment.

Participant Groups

Group I: De-intensified Cisplatin-based Chemoradiation Experimental Treatment 2 Interventions

This is a non-randomized study, with all patients undergoing de-intensified post-operative cisplatin-based chemoradiation. Dosage level and duration of administration will be determined by whether the patient is high risk or not as assessed by the treating investigator.

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?

Cedars-Sinai Medical Center

Lead Sponsor

Trials

523

Recruited

165,000+

Findings from Research

Patients with locally advanced oropharyngeal squamous cell carcinoma who received cisplatin (CDDP) had a significantly better 2-year overall survival rate compared to those treated with cetuximab (CTX), with a hazard ratio of 1.68 indicating higher mortality for CTX users.

Cisplatin also resulted in lower overall treatment costs compared to CTX and carboplatin, despite higher rates of antiemetic use and hospital visits for side effects, suggesting it may be a more cost-effective option for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing outcomes of concurrent chemotherapy regimens in patients 65 years old or older with locally advanced oropharyngeal carcinoma. Amini, A., Eguchi, M., Jones, BL., et al.[2023]

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 18 patients with operable stage III and IV head and neck cancers, the combination of preoperative cis-platinum (cis-DDP) and radiation therapy resulted in a high response rate, with 89% of patients achieving a complete or partial response, and 72% showing complete responses in primary tumors.

The treatment was well-tolerated, with low site-related morbidity (15%) and a notable number of patients (5 out of 10) having pathologically negative tumors after surgery, indicating effective tumor reduction and safety of the regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative simultaneously administered cis-platinum plus radiation therapy for advanced squamous cell carcinoma of the head and neck. Slotman, GJ., Cummings, FJ., Glicksman, AR., et al.[2019]

In a study of 153 patients with advanced oropharyngeal and nasopharyngeal carcinoma, adding weekly cisplatin to radiotherapy significantly improved overall survival, with a median survival of 27 months for radiotherapy alone compared to not reached for the chemoradiotherapy group.

While chemoradiotherapy showed higher complete response rates (80.5% vs. 67.1%) and better overall survival, it also resulted in increased toxicity, with 40% of patients experiencing severe side effects compared to 16% in the radiotherapy group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concomitant chemoradiation versus radical radiotherapy in advanced squamous cell carcinoma of oropharynx and nasopharynx using weekly cisplatin: a phase II randomized trial. Sharma, A., Mohanti, BK., Thakar, A., et al.[2022]

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 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 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 III trial involving 237 patients with inoperable head and neck cancer, intra-arterial (IA) cisplatin did not show improved tumor control compared to intravenous (IV) cisplatin, despite a higher dose being administered via IA.

Patients receiving IV cisplatin experienced worse late dysphagia, indicating a potential safety concern with IV administration, while overall survival and locoregional control were similar between both treatment methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Late follow-up of the randomized radiation and concomitant high-dose intra-arterial or intravenous cisplatin (RADPLAT) trial for advanced head and neck cancer. Heukelom, J., Lopez-Yurda, M., Balm, AJ., et al.[2018]

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]

References

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

Comparing outcomes of concurrent chemotherapy regimens in patients 65 years old or older with locally advanced oropharyngeal carcinoma. [2023]

2. 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]

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

Preoperative simultaneously administered cis-platinum plus radiation therapy for advanced squamous cell carcinoma of the head and neck. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Concomitant chemoradiation versus radical radiotherapy in advanced squamous cell carcinoma of oropharynx and nasopharynx using weekly cisplatin: a phase II randomized trial. [2022]

5. 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]

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

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

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

Late follow-up of the randomized radiation and concomitant high-dose intra-arterial or intravenous cisplatin (RADPLAT) trial for advanced head and neck cancer. [2018]

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

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