Reduced Radiation + Cisplatin for Oropharyngeal Cancer

(EVADER Trial)

Recruiting at 13 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

103 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to find out whether radiotherapy to some of the lymph node areas can be safely omitted to decrease side effects without increasing the risk of the tumour coming back.

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.

What data supports the effectiveness of the treatment Reduced Radiation + Cisplatin for Oropharyngeal Cancer?

Research shows that cisplatin, when used with radiation, is a standard treatment for advanced oropharyngeal cancer, and it has been effective in improving outcomes. Studies indicate that cisplatin enhances the effects of radiation, making it a powerful combination for treating this type of cancer. ^{1 2 3 4 5}

Is the combination of reduced radiation and cisplatin generally safe for treating oropharyngeal cancer?

Studies show that using cisplatin with radiation can cause side effects like low white blood cell counts, nausea, and vomiting. However, some research suggests that this combination is generally well tolerated, though severe side effects have been noted in certain cases. ^{2 6 7 8 9}

How is the treatment of reduced radiation and cisplatin unique for oropharyngeal cancer?

This treatment combines reduced radiation with cisplatin, a chemotherapy drug, to potentially minimize side effects while maintaining effectiveness. It differs from standard treatments by using a lower radiation dose, which may reduce the risk of severe side effects like mucositis (painful inflammation and ulceration of the mucous membranes) and dermitis (skin inflammation). ^{1 2 4 10 11}

Research Team

Scott Bratman

Principal Investigator

Princess Margaret Cancer Centre, Toronto, ON

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: Two Treatment Options Experimental Treatment 2 Interventions

Option #1 - Radiotherapy 35 fractions, 5/wk, 7 wks 70Gy/56Gy Cisplatin 100mg/m2 on day 1, 22 and 43 or 40mg mg/m2/wk for 7 wks Option #2 - Radiation only-35 fraction, 6/wk, 6wks 70Gy/56Gy

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+

Findings from Research

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]

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 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 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 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 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]

References

1. 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]

2. 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]

3. England pubmed.ncbi.nlm.nih.gov

Survival outcomes in patients with oropharyngeal cancer treated with carboplatin/paclitaxel and concurrent radiotherapy. [2018]

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

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

5. United States 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. [2019]

6. Japan pubmed.ncbi.nlm.nih.gov

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

7. England pubmed.ncbi.nlm.nih.gov

High-dose versus weekly cisplatin definitive chemoradiotherapy for HPV-related oropharyngeal squamous cell carcinoma of the head and neck. [2019]

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

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

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

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

10. 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]

11. Ireland 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. [2019]