Transoral Surgery + Radiation Therapy + Chemotherapy for Oropharyngeal Cancer

Recruiting at 57 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

519 Participants Needed

Trial Summary

What is the purpose of this trial?

This randomized phase II trial studies how well transoral surgery followed by low-dose or standard-dose radiation therapy works in treating patients with human papilloma virus (HPV) positive stage III-IVA oropharyngeal cancer. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy with chemotherapy may kill any tumor cells that remain after surgery. It is not yet known how much extra treatment needs to be given after surgery.

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 effectiveness of the treatment Transoral Surgery + Radiation Therapy + Chemotherapy for Oropharyngeal Cancer?

Research suggests that combining transoral surgery with chemotherapy and radiation therapy can be effective for treating oropharyngeal cancer. Transoral robotic surgery, a minimally invasive approach, has shown promising results in reducing complications and improving outcomes, especially when combined with advanced radiation techniques. ^{1 2 3 4 5}

Is the combination of transoral surgery, radiation therapy, and chemotherapy safe for treating oropharyngeal cancer?

Transoral robotic surgery (TORS) is considered a safe technique for treating oropharyngeal cancer, with studies supporting its safety and effectiveness. It uses precise tools to perform surgery with fewer complications compared to traditional methods. However, patient selection is important to ensure safety, considering factors like other health conditions and anatomy. ^{4 6 7 8 9}

How is the treatment of transoral surgery combined with radiation and chemotherapy unique for oropharyngeal cancer?

This treatment is unique because it uses transoral surgery, which accesses and removes the tumor through the mouth, minimizing the impact on appearance and function compared to traditional open surgery. It combines this minimally invasive approach with radiation and chemotherapy to enhance treatment effectiveness. ^{3 4 10 11 12}

Research Team

Robert Ferris

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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) 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]

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 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]

References

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

Quality of Life Implications After Transoral Robotic Surgery for Oropharyngeal Cancers. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Transoral robotic surgery and a paradigm shift in the management of oropharyngeal squamous cell carcinoma. [2018]

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

Neoadjuvant chemotherapy and transoral surgery as a definitive treatment for oropharyngeal cancer: A feasible novel approach. [2018]

4. England 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). [2020]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Development of an online, patient-centred decision aid for patients with oropharyngeal cancer in the transoral robotic surgery era. [2019]

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

Trimodality therapy for oropharyngeal cancer in the TORS era: Is there a cohort that may benefit? [2020]

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

Oncologic outcomes of transoral robotic surgery for HPV-negative oropharyngeal carcinomas. [2021]

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

Is There a Role for Robotic Surgery in the Treatment of Head and Neck Cancer? [2018]

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

Comparison of functional outcomes and quality of life between transoral surgery and definitive chemoradiotherapy for oropharyngeal cancer. [2021]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Transoral surgery (TOS) in oropharyngeal cancer: Different tools, a single mini-invasive philosophy. [2019]

11. India 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. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Interventions for the treatment of oral and oropharyngeal cancers: surgical treatment. [2018]