Induction Chemotherapy in Locally Advanced Hypopharyngeal Carcinoma: a Randomised Phase 3 Trial

Sponsor

Sun Yat-sen University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04502641

Collaborator

(none)

160

Enrollment

Location

Arms

Anticipated Duration (Months)

2.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Hypopharyngeal cancer is an important part of head and neck cancer, with more than 80,000 new cases in 2018. And it is a highly aggressive cancer often diagnosed at an advanced stage. which expresses poor survival, the 5-year overall survival (OS) is about only 30%-35%. Given the complexity of these tumors, their surrounding structures, the frequent comorbidities, and the improvement of patients' requirements for quality of life, a multidisciplinary treatment approach should be applied to achieve the best oncological outcomes and to improve functional results. This benefi t of induction chemotherapy has been recorded in patients with both resectable and unresectable disease. It has also been observed in patients with laryngeal cancer treated for organ preservation. However, whether the addition of induction chemotherapy to chemoradiotherapy improves efficacy compared with chemoradiotherapy alone is unclear in hypopharyngeal cancer.We tried to observe the clinical treatment efficiency, toxic and side effects, progression-free survival time, overall survival time and quality of life of anlotinib in the treatment of patients with refractory head and neck carcinoma. Provide patients with a more optimal treatment plan and improve survival.

Condition or Disease	Intervention/Treatment	Phase
Hypopharyngeal Cancer	Drug: Docetaxel Drug: 5-fluorouracil Drug: Cisplatin Radiation: Intensity Modulated Radiation Therapy Drug: Platinum	Phase 3

Detailed Description

We will prospectively collect 160 patients who were randomly assigned (in a 1:1 ratio) to receive either induction chemotherapy followed by concurrent chemoradiotherapy (group A) or definitive concurrent chemoradiotherapy (group B). Data will be stored in a private database. The process of data collection will be supervised and regular data examination will be performed.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

160 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized Phase III Comparing Sequential Therapy With Induction Chemotherapy/Chemoradiation To Cisplatinum-Based Chemoradiotherapy in Locally Advanced Hypopharyngeal Carcinoma

Anticipated Study Start Date :

Aug 1, 2020

Anticipated Primary Completion Date :

Aug 1, 2023

Anticipated Study Completion Date :

Aug 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I Patients receive induction chemotherapy with docetaxel-based, with or without cisplatin or fluorouracil. Treatment repeats every 21 days for 3 courses. Then, patients receive cisplatin on day 1 day 21, 3 weeks as one cycle and undergo concurrent radiotherapy once daily, 5 days a week, for 6 to 7 weeks.	Drug: Docetaxel 60mg/m2 on day 1, 3 weeks as one cycle, for 3 cycles. Other Names: Taxol Drug: 5-fluorouracil 600 mg/m² per day as a continuous 120 h infusion on days 1-5, 3 weeks as one cycle, for 3 cycles. Drug: Cisplatin 60mg/m2 on day 1, 3 weeks as one cycle, for 3 cycles. Radiation: Intensity Modulated Radiation Therapy The treatment consisted of definitive radiotherapy with conventional fractionation, a total dose of 68-70 Gy to PTVp, 62-68 Gy to PTVn, 60-62 Gy to PTV-HR, and 50-54 Gy to PTV-LR. Drug: Platinum 100mg/m2 on day 1, 3 weeks as one cycle, during radiotherapy.
Active Comparator: Arm II Patients receive cisplatin on day 1 day 21, 3 weeks as one cycle and undergo concurrent radiotherapy once daily, 5 days a week, for 6 to 7 weeks.	Radiation: Intensity Modulated Radiation Therapy The treatment consisted of definitive radiotherapy with conventional fractionation, a total dose of 68-70 Gy to PTVp, 62-68 Gy to PTVn, 60-62 Gy to PTV-HR, and 50-54 Gy to PTV-LR. Drug: Platinum 100mg/m2 on day 1, 3 weeks as one cycle, during radiotherapy.

Arm

Intervention/Treatment

Experimental: Arm I

Patients receive induction chemotherapy with docetaxel-based, with or without cisplatin or fluorouracil. Treatment repeats every 21 days for 3 courses. Then, patients receive cisplatin on day 1 day 21, 3 weeks as one cycle and undergo concurrent radiotherapy once daily, 5 days a week, for 6 to 7 weeks.

Drug: Docetaxel

60mg/m2 on day 1, 3 weeks as one cycle, for 3 cycles.

Other Names:

Taxol

Drug: 5-fluorouracil

600 mg/m² per day as a continuous 120 h infusion on days 1-5, 3 weeks as one cycle, for 3 cycles.

Drug: Cisplatin

60mg/m2 on day 1, 3 weeks as one cycle, for 3 cycles.

Radiation: Intensity Modulated Radiation Therapy

The treatment consisted of definitive radiotherapy with conventional fractionation, a total dose of 68-70 Gy to PTVp, 62-68 Gy to PTVn, 60-62 Gy to PTV-HR, and 50-54 Gy to PTV-LR.

Drug: Platinum

100mg/m2 on day 1, 3 weeks as one cycle, during radiotherapy.

Active Comparator: Arm II

Patients receive cisplatin on day 1 day 21, 3 weeks as one cycle and undergo concurrent radiotherapy once daily, 5 days a week, for 6 to 7 weeks.

Radiation: Intensity Modulated Radiation Therapy

The treatment consisted of definitive radiotherapy with conventional fractionation, a total dose of 68-70 Gy to PTVp, 62-68 Gy to PTVn, 60-62 Gy to PTV-HR, and 50-54 Gy to PTV-LR.

Drug: Platinum

100mg/m2 on day 1, 3 weeks as one cycle, during radiotherapy.

Outcome Measures

Primary Outcome Measures

Progression-free survival (RFS) [3 month]
Measured from the date of treatment end to recurrent/residual tumor was diagnose or to the time of the last follow-up, whichever occurred first，by means of computed tomography (CT) or magnetic resonance imaging (MRI) at each follow-up.

Secondary Outcome Measures

Overall-survival (OS) [3 month]
Defined as the interval between the time of treatment end to death or to the last date of follow-up，by means of computed tomography (CT) or magnetic resonance imaging (MRI) at each follow-up.
Adverse events rate [One month]
Adverse events during the treatment period using Common Terminology Criteria for Adverse Events (CTCAE) (version 5.0).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

1. Male or female, aged 18 to 75 years; 2. Performance status (PS) score ≤ 2 points;

The expected survival period is more than 3 months; 4. Patients have histopathologically confirmed hypopharyngeal squamous cell carcinoma, including the piriform fossa, postcricoid region, and posterior pharyngeal wall with stage III and IVA-B (TNM stageT1-2N1-3M0/T3-4aN0-3M0) according to the AJCC 8th edition; 5. With measurable lesions: According to the evaluation criteria for the efficacy of solid tumors (Response Evaluation Criteria In Solid Tumors 1.1), the patient has at least one measurable lesion. The measurable lesion should not have received local treatment such as radiotherapy (target lesion located in the previous radiotherapy area, if it is confirmed that significant progress has occurred , And comply with evaluation standard, can also be used as target lesions); 6. No previous anti-tumor therapy, including anti-angiogenesis therapy, such as pazopanib, sunitinib, sorafenib, regorafenib, etc.; 7. Sufficient liver function: total bilirubin ≤ upper limit of normal value (ULN); glutamic oxalacetic transaminase (AST) and glutamic-pyruvic transaminase (ALT) ≤ 2 times upper limit of normal value (ULN); alkaline phosphatase ≤ 5 times upper limit of normal value (ULN); 8. Adequate renal function: creatinine clearance rate ≥80 mL/min; 9. Adequate blood function: absolute neutrophil count (ANC) ≥2×109/L, platelet count ≥100×109/L and hemoglobin ≥9g/dL; 10. No serious heart, lung and other important organ dysfunction; 11. Women of childbearing age must have taken reliable contraceptive measures; pregnancy tests (serum or urine) are negative within 7 days before enrollment, and must be non-lactating patients; and are willing to adopt appropriate during the test and within 6 months after the last treatment Methods of contraception. For men, it is necessary to agree to use appropriate methods of contraception or surgical sterilization during the trial and 8 weeks after the last dose; 12. The subjects voluntarily joined the study and signed an informed consent form with good compliance and cooperated with the follow-up.

Exclusion Criteria:

1. Have a history of other cancers in the past five years, radical or untreated prostate cancer (Gleason score ≤ 6), or complete treatment of breast ductal carcinoma in situ, except for patients with cured skin basal cell carcinoma or squamous cell skin cancer; 2. Patients with target lesions who have received radiation therapy or surgery (except biopsy); 3. Treatment with palliative intent; 4. A history of previous radiotherapy, chemotherapy, or surgery (except diagnostic) to the primary tumor or nodes; 5. Any severe coexisting disease.