Reduced Radiation + Cisplatin for Oropharyngeal Cancer

(EVADER Trial)

Not currently recruiting at 14 trial locations

Overseen By Wendy Parulekar

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Canadian Cancer Trials Group

Disqualifiers: Previous head/neck cancer treatment, unknown primary

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: 35

Duration: 6-7 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the safety of reducing radiation to certain lymph node areas in individuals with oropharyngeal cancer, a type of throat cancer caused by HPV. Researchers seek to discover if lowering radiation can reduce side effects without increasing the risk of cancer recurrence. Participants will receive either chemotherapy with Cisplatin plus radiation or only radiation. Individuals with HPV-related oropharyngeal cancer who have not undergone previous treatment for head and neck cancer may be suitable candidates. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications for 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.

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

Research shows that patients receiving cisplatin may experience side effects. Studies have found that weekly cisplatin can lead to more blood-related side effects than a three-week schedule. However, doctors select the schedule they believe is best for each patient.

Radiation therapy effectively treats oropharyngeal cancer, but it often comes with significant side effects, such as soreness, difficulty swallowing, or changes in taste. Despite these side effects, many patients continue with radiation because it can help control the cancer.

In this trial, both cisplatin and radiation are used together to treat oropharyngeal cancer. While both treatments have side effects, they are commonly used and studied in cancer care. This trial is in an early phase, meaning the treatments have been tested in other studies, but researchers continue to work on making them safer and more effective when used together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for oropharyngeal cancer because it explores a reduced radiation approach combined with or without Cisplatin, which could potentially minimize side effects associated with traditional high-dose radiation treatments. Unlike standard treatments that often involve high radiation doses to both high-risk and elective areas, this approach adjusts the radiation volume and dosage, aiming to maintain effectiveness while reducing harm to surrounding healthy tissues. This strategy could lead to better quality of life for patients by minimizing common radiation-related complications, such as difficulty swallowing and dry mouth.

What evidence suggests that reduced radiation and Cisplatin could be effective for oropharyngeal cancer?

Research has shown that using a lower dose of radiation with the drug cisplatin effectively treats HPV-related throat cancer. One study found that patients had high survival rates, with about 96.7% living for at least two years with this combined treatment. In this trial, participants may receive either the combined treatment of reduced radiation and cisplatin or reduced radiation alone. Using reduced radiation alone, with a method called intensity-modulated radiotherapy (IMRT), also yields strong results, with survival rates similar to other advanced treatments. Both approaches aim to reduce side effects while maintaining effectiveness, making them promising options for patients seeking effective cancer treatments with potentially fewer side effects. ^{6 7 8 9 10}

Who Is on the Research Team?

Scott Bratman

Principal Investigator

Princess Margaret Cancer Centre, Toronto, ON

Are You a Good Fit for This Trial?

This trial is for adults with low-risk HPV-related oropharyngeal squamous cell carcinoma who haven't had chemo or radiotherapy for head and neck cancer. They must be fit enough for treatment, able to follow up, use effective contraception, and complete questionnaires in English or French.

Inclusion Criteria

I am using a highly effective method of birth control.

Patient must consent to provision of, and investigator(s) must confirm location and commit to obtain a representation of formalin-fixed paraffin block of non-cytology tumour tissue in order that the specific correlative marker assays described in Section 12 (Correlative Studies) may be conducted. Please see the Correlative Manual for details

My throat cancer is caused by HPV.

Exclusion Criteria

My cancer's origin is unknown.

I have had chemotherapy or radiotherapy for head and neck cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive radiotherapy with or without chemotherapy over 6-7 weeks

6-7 weeks

35 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• Radiation

Trial Overview The study tests if omitting radiotherapy from certain lymph node areas in patients with specific oral cancers can reduce side effects without increasing the risk of cancer returning. It involves radiation and Cisplatin as treatments.

How Is the Trial Designed?

Group I: Experimental arm Experimental Treatment 2 Interventions

This is a non-randomized, single-arm study evaluating elective volume-adjusted de-escalation radiotherapy. Patients receive one of two treatment options, based on treating physician discretion. Both options are considered part of a unified treatment strategy and analyzed as a single arm. * Option 1 (Chemoradiotherapy): Radiotherapy: 70 Gy to the high-risk volume and 56 Gy to the elective volume, delivered in 35 fractions over 7 weeks (5 fractions/week) Cisplatin: Either 100 mg/m² on days 1, 22, and 43 or 40 mg/m² weekly for 7 weeks * Option 2 (Radiotherapy Alone): Radiotherapy: 70 Gy to the high-risk volume and 56 Gy to the elective volume, delivered in 35 fractions over 6 weeks (6 fractions/week)

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?

Canadian Cancer Trials Group

Lead Sponsor

Trials

135

Recruited

70,300+

Published Research Related to This Trial

In a study of 52 patients with advanced nodal disease (N2 to N3) from upper aerodigestive tract carcinoma, targeted chemoradiation using the RADPLAT protocol resulted in a 59% clinical complete response rate in evaluable heminecks.

The combination of targeted chemoradiation and planned selective neck dissection achieved a high regional disease control rate of 91%, indicating that this approach is effective in managing advanced neck disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of targeted chemoradiation and planned selective neck dissection to control bulky nodal disease in advanced head and neck cancer. Robbins, KT., Wong, FS., Kumar, P., et al.[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 160 patients with advanced oropharyngeal squamous cell carcinoma treated with carboplatin, paclitaxel, and radiation over 10 years, the overall survival rates were 81.7% at 3 years and 70.7% at 5 years, indicating effective treatment outcomes.

The treatment demonstrated an acceptable side effect profile, with the most common adverse effect being acute dysphagia (75.25%), and only 11.9% of patients experiencing significant hematologic toxicities, suggesting carboplatin may be a safer alternative to cisplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival outcomes in patients with oropharyngeal cancer treated with carboplatin/paclitaxel and concurrent radiotherapy. Roskies, M., Kay-Rivest, E., Mascarella, MA., 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]

In a study of 83 patients with oropharyngeal, hypopharyngeal, or laryngeal cancer, treatment with weekly cisplatin during radiotherapy resulted in a 2-year local control rate of 84% and overall survival rate of 82%.

The 5-year survival estimates showed a local control rate of 79%, overall survival of 69%, and disease-specific survival of 76%, indicating that this treatment regimen is effective over the long term.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patterns of relapse following definitive treatment of head and neck squamous cell cancer by intensity modulated radiotherapy and weekly cisplatin. Loimu, V., Collan, J., Vaalavirta, L., 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]

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 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]

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]

Citations

1. nrgoncology.org nrgoncology.org/Home/News/Post/reduced-dose-radiation-with-cisplatin-improves-outcomes-for-hpv-associated-oropharyngeal-carcinoma-patients-on-nrg-oncology-study-justifies-phase-iii-trial

Reduced-Dose Radiation with Cisplatin Improves Outcomes f 2-year overall survival rates were 96.7% and 97.3% for the IMRT+C and the IMRT alone arms, respectively. While more grade 3-4 acute toxicities ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8078254/

Reduced-Dose Radiation Therapy for HPV-Associated ... Reducing radiation treatment dose could improve the quality of life (QOL) of patients with good-risk human papillomavirus–associated oropharyngeal squamous ...

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

Weekly Cisplatin Cycles and Outcomes for Chemoradiation ... These findings suggest that missing several cycles of weekly cisplatin is associated with worse survival, even among those with p16-negative tumors.

4. 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 ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0360301625004754

A Phase 1 Study of Deintensified Hypofractionated ... Published phase 2 results of reduced dose radiation therapy (RT) of 60 Gy with weekly cisplatin have shown excellent outcomes with 2- to 3-year progression-free ...

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/S0305737223000774

Managing cisplatin-ineligible patients with resected, high- ... A cumulative cisplatin dose of ≥ 200 mg/m2 has been associated with significantly longer OS than a cumulative dose of < 200 mg/m2 [16], [27]. In a retrospective ...

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. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.999027/full

Efficacy and safety of weekly versus triweekly cisplatin ... Patients who were administered weekly cisplatin were at a higher risk of hematological toxicity compared with patients who received the chemotherapy triweekly.