Chemoradiation for Oropharyngeal Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a lower-dose version of cisplatin-based chemoradiation (a combination of chemotherapy and radiation therapy) is as effective but with fewer side effects for people with HPV-related throat cancer. The trial targets patients who have undergone surgery to remove visible cancer cells and have high-risk features that might require more intense treatment. Individuals with certain risk factors, such as multiple affected lymph nodes or large tumors, may be suitable for this study. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to important findings.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Studies have shown that cisplatin-based chemoradiation can cause side effects such as nausea, vomiting, and weight loss. However, these side effects are similar to those of comparable treatments. Research indicates that most patients tolerate the treatment well, though some may experience more serious issues like kidney problems or hearing loss, particularly if they have pre-existing health conditions. This trial employs a milder version of the treatment, aiming to reduce these side effects while still effectively combating cancer. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for oropharyngeal cancer?

Researchers are excited about the de-intensified cisplatin-based chemoradiation for oropharyngeal cancer because it aims to reduce the intensity of treatment while maintaining effectiveness. Unlike traditional approaches that often involve higher doses and longer durations, this treatment adjusts the dosage and administration duration based on the patient's risk level, potentially minimizing side effects. This personalized approach could lead to a better quality of life for patients without compromising treatment efficacy, making it a promising option in the fight against oropharyngeal cancer.

What evidence suggests that this de-intensified chemoradiation treatment could be effective for oropharyngeal cancer?

Research has shown that combining the drug cisplatin with radiation is crucial for treating oropharyngeal cancer, which affects the throat area. Studies have found this approach to be the most effective for advanced cases, as it helps shrink the tumor and prevent the cancer from spreading. For patients with oropharyngeal cancer linked to HPV, this treatment has produced excellent results, particularly when the cancer is detected early. Even older patients who can tolerate the treatment have experienced positive outcomes. This trial will investigate whether a lower dose of cisplatin-based chemoradiation can be equally effective, potentially resulting in fewer side effects. ^{6 7 8 9 10}

Who Is on the Research Team?

Zachary S. Zumsteg

Principal Investigator

Cedars-Sinai Medical Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11513364/

Retrospective study of cisplatin plus radiotherapy toxicities ... A total of 274 (84%) patients were compliant and received the planned dose of cisplatin. Overall, 957 adverse events were reported in 98.2% of ...

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

Weekly Cisplatin Cycles and Outcomes for Chemoradiation ... This cohort study evaluates the association between the number of weekly cisplatin cycles and outcomes in patients receiving chemoradiation ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1368837518300460

Clinical outcomes and prognostic factors in cisplatin versus ... Randomized trials evaluating cisplatin versus cetuximab chemoradiation (CRT) for p16+ oropharyngeal cancer (OPC) have yet to report preliminary data.

4. thegreenjournal.com thegreenjournal.com/article/S0167-8140(22)04234-7/fulltext

Disease outcome and associated factors after definitive ... Definitive concomitant cisplatin-based chemoradiotherapy (CRT) is the current gold standard for most patients with advanced stage head and ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5384883/

The toxicity and efficacy of concomitant chemoradiotherapy ... A subgroup of patients with oropharyngeal squamous cell carcinoma aged 70 and older deemed fit for cisplatin-based chemoradiation had excellent outcomes, with ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4146684/

Cisplatin in cancer therapy: molecular mechanisms of action Cisplatin binds to the N7 reactive center on purine residues and as such can cause deoxyribonucleic acid (DNA) damage in cancer cells, blocking cell division ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05050162

NCT05050162 | Comparing Cisplatin Every Three Weeks ... This phase II/III trial compares whether cisplatin given weekly with radiation therapy is better tolerated than cisplatin given every three weeks with ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S0928098724002525

Advances in understanding cisplatin-induced toxicity The risk of developing cisplatin-induced toxicity could be related to pre-existing conditions, including kidney disease, hearing impairment, ...

9. cell.com cell.com/iscience/fulltext/S2589-0042(25)01609-8

Senataxin regulates cisplatin resistance through an R-loop ... Long term treatment with cisplatin results in resistant clones which show differential expression of R-loop regulators. In order to investigate platinum ...

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9169397/

Comparing the efficacy and safety of cisplatin and other ... The risk of nausea, vomiting and weight loss was higher in the cisplatin group; however, there was no significant difference in the other non-hematological and ...