Transoral Surgery + Radiation Therapy + Chemotherapy for Oropharyngeal Cancer

Not currently recruiting at 58 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Eastern Cooperative Oncology Group

Disqualifiers: Prior radiation, Uncontrolled diabetes, 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: 16

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of surgery followed by radiation—and sometimes chemotherapy—in treating a type of throat cancer linked to the human papilloma virus (HPV). Researchers seek to determine if varying levels of radiation, combined with surgery, can more effectively target and eliminate any remaining cancer cells. The trial includes multiple treatment plans based on the cancer's risk level, ranging from observation after surgery to chemotherapy with radiation. Individuals with newly diagnosed, doctor-confirmed HPV-positive stage III-IVA oropharyngeal cancer may be eligible to participate. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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 trial's treatments are likely to be safe?

Research has shown that transoral surgery is generally safe for treating throat cancer. In studies, patients experienced no major complications, and most, including older individuals, recovered well, with results similar to younger patients.

After surgery, intensity-modulated radiation therapy (IMRT) is often used. Studies indicate that while IMRT can cause some side effects, they are usually manageable, and the treatment is effective.

For patients at high risk, the treatment plan includes cisplatin, a common chemotherapy drug. Side effects of cisplatin include nausea, vomiting, and mouth sores. However, these are common with many chemotherapy treatments and can often be managed with medication.

Overall, these treatments have demonstrated a good safety record in previous studies, suggesting they are well-tolerated by most patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it explores a new approach to treating oropharyngeal cancer by combining transoral surgery with different levels of post-surgical interventions tailored to the patient's risk level. Unlike the standard of care, which often involves more aggressive treatments like high-dose radiation and chemotherapy for all patients, this trial aims to personalize treatment intensity. For low-risk patients, observation after surgery could minimize unnecessary side effects. Intermediate-risk patients might benefit from lower or standard doses of radiation therapy, balancing effectiveness with reduced toxicity. High-risk patients receive a more comprehensive approach, with intensified radiation and chemotherapy, potentially improving outcomes while still being mindful of side effects. This tailored strategy could lead to more efficient and patient-friendly cancer care.

What evidence suggests that this trial's treatments could be effective for oropharyngeal cancer?

Research has shown that surgery through the mouth, known as transoral surgery, effectively treats HPV-positive throat cancer, with survival rates exceeding 93% for this specific disease. In this trial, all participants will undergo transoral surgical resection of the oropharyngeal tumor. After surgery, some participants will receive a precise form of radiation therapy called IMRT, which controls the tumor effectively, with a high response rate of 99.3% four months after treatment. For high-risk patients in this trial, adding the chemotherapy drug cisplatin to radiation therapy has improved results, with studies reporting very high survival rates. These treatments together show promising results for patients with throat cancer. ^{2 3 6 7 8}

Who Is on the Research Team?

Robert Ferris

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

This trial is for adults with HPV-positive stage III-IVA oropharyngeal cancer. Participants must have resectable disease, good performance status (ECOG 0 or 1), and proper organ function. They should not have had prior radiation above the clavicles, be pregnant, or have uncontrolled conditions like diabetes. Contraception is advised for those who can bear children.

Inclusion Criteria

Biopsy-proven p16+ oropharynx cancer; the histologic evidence of invasive squamous cell carcinoma may have been obtained from the primary tumor or metastatic lymph node

Carcinoma of the oropharynx associated with HPV as determined by p16 protein expression using immunohistochemistry (IHC) performed by a Clinical Laboratory Improvement Amendments (CLIA) approved laboratory; using p16 antibody obtained from Roche mtm laboratories AG (CINtec, clone E6H4) is recommended

You had a stroke or a mini-stroke within the last 6 months.

Exclusion Criteria

Prior radiation above the clavicles

Evidence of extensive or 'matted/fixed' pathologic adenopathy on preoperative imaging

Uncontrolled diabetes, uncontrolled infection despite antibiotics or uncontrolled hypertension within 30 days prior to pre-registration

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery

Participants undergo transoral surgical resection of the oropharyngeal tumor

1 week

1 visit (in-person)

Radiation Therapy

Participants receive risk-adjusted intensity modulated radiation therapy (IMRT) based on their risk classification

5-7 weeks

5 visits per week (in-person)

Chemotherapy

High-risk patients receive cisplatin intravenously during radiation therapy

6-7 weeks

7 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Every 3 months for 2 years, then every 6 months for 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Cisplatin
• Intensity-modulated radiation therapy
• Transoral surgery

Trial Overview The study tests how well transoral surgery followed by low-dose or standard-dose radiation therapy works when treating HPV-related throat cancer. It also examines if adding chemotherapy with drugs like cisplatin or carboplatin improves outcomes after surgery.

How Is the Trial Designed?

Group I: Arm S (Surgery) then Arm D (High risk, IMRT, chemotherapy) Experimental Treatment 4 Interventions

Patients undergo transoral surgical resection of the oropharyngeal tumor. After transoral surgical resection of the oropharyngeal tumor, high risk patients then receive IMRT (66Gy) QD five days a week for 6-7 weeks. Patients also receive cisplatin IV over 60 minutes on days 1, 8, 15, 22, 29, 36, and 43 during radiation therapy.

Group II: Arm S (Surgery) then Arm C (Intermediate risk, standard-dose IMRT) Experimental Treatment 2 Interventions

Patients undergo transoral surgical resection of the oropharyngeal tumor. After transoral surgical resection of the oropharyngeal tumor, intermediate risk patients receive standard-dose IMRT (60 Gy) QD five days a week for 6 weeks.

Group III: Arm S (Surgery) then Arm B (Intermediate risk, low-dose IMRT) Experimental Treatment 2 Interventions

Patients undergo transoral surgical resection of the oropharyngeal tumor. After transoral surgical resection of the oropharyngeal tumor, intermediate risk patients receive low-dose IMRT (50 Gy) QD five days a week for 5 weeks.

Group IV: Arm S (Surgery) then Arm A (Low risk, observation) Experimental Treatment 1 Intervention

Patients undergo transoral surgical resection of the oropharyngeal tumor. After transoral surgical resection of the oropharyngeal tumor, low risk patients are under observation.

Who Is Running the Clinical Trial?

Eastern Cooperative Oncology Group

Lead Sponsor

Trials

272

Recruited

153,000+

ECOG-ACRIN Cancer Research Group

Lead Sponsor

Trials

122

Recruited

160,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Transoral robotic surgery (TORS) for HPV-negative oropharyngeal squamous cell carcinoma (OPSCC) showed promising oncologic outcomes, with a 3-year overall survival rate of 85.5% and disease-free survival rate of 73.6% among 56 patients studied.

The TORS approach resulted in low perioperative morbidity, with only 1.8% experiencing mortality and a 5.4% rate of long-term gastrostomy, indicating it is a safer surgical option compared to traditional methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oncologic outcomes of transoral robotic surgery for HPV-negative oropharyngeal carcinomas. Parhar, HS., Weinstein, GS., O'Malley, BW., et al.[2021]

In a study of 58 patients with early oropharyngeal cancer who underwent transoral robotic surgery, the two-year disease-free survival rate was 88.2% for those treated upfront, while it was 55.5% for those in the salvage cohort, indicating effective locoregional control especially in HPV-negative cases.

The overall survival rate was 86.05%, but the presence of positive surgical margins significantly impacted disease-free survival, highlighting the importance of achieving clear margins during surgery for better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of Outcomes following TORS in a Mixed Cohort of Recurrent and New T1-T2 Oropharyngeal Cancer- A Single Institution Study. Panda, NK., Kapoor, A., Goel, N., et al.[2023]

Transoral Robotic Surgery (TORS) for Stage III-IV HPV negative oropharyngeal cancer showed promising long-term results, with 81.7% of patients remaining disease-free and an overall survival rate of 91.5% after an average follow-up of 48 months.

The study suggests that TORS can effectively intensify treatment while minimizing the toxic effects associated with higher doses of traditional radiotherapy or chemoradiotherapy, leading to improved oncological outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oncological outcome following initiation of treatment for stage III and IV HPV negative oropharyngeal cancers with transoral robotic surgery (TORS). Dabas, S., Gupta, K., Sharma, AK., et al.[2020]

Transoral robotic surgery (TORS) is an effective and safe treatment option for oropharyngeal and select supraglottic tumors, particularly beneficial for younger patients with HPV-positive oropharyngeal cancer.

Current literature supports the safety and efficacy of TORS, and ongoing level 1 evidence trials aim to further validate its use, emphasizing the importance of careful patient selection based on individual health and anatomical factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is There a Role for Robotic Surgery in the Treatment of Head and Neck Cancer? Byrd, JK., Ferris, RL.[2018]

In a study of 17 patients with advanced oropharyngeal cancer, treatment with neoadjuvant chemotherapy followed by transoral surgery (TOS) resulted in a high disease-specific survival rate of 94.1% at 3 years, with 16 out of 17 patients alive without recurrence after a median follow-up of 31 months.

This approach demonstrates that combining chemotherapy with TOS and neck dissection is a feasible and effective strategy for managing moderately advanced oropharyngeal cancer, potentially allowing for the postponement of radiotherapy for cases with adverse features.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant chemotherapy and transoral surgery as a definitive treatment for oropharyngeal cancer: A feasible novel approach. Sadeghi, N., Li, NW., Taheri, MR., et al.[2018]

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. sciencedirect.com sciencedirect.com/science/article/pii/S0167814022042347

Disease outcome and associated factors after definitive ... Definitive cisplatin-based CRT has become the treatment of choice in advanced stage HNSCC that arise outside the oral cavity and larynx. This organ-preserving ...

3. 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 ...

4. 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 ...

5. 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.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6940183/

Efficacy and safety of cisplatin for the management of adult ... The findings of this study will provide convinced evidence of cisplatin for adult patients with OC, and provide recommendations for clinical practice.

7. 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 ...

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 ...