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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Hypopharyngeal Cancer
• Intervention / Treatment: Drug: Docetaxel; Drug: 5-fluorouracil; Drug: Cisplatin; Radiation: Intensity Modulated Radiation Therapy; Drug: Platinum

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 Type: Interventional
• Enrollment (Anticipated): 160
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Yong Chen; Phone Number: +862087755766; Email: chenyong@mail.sysu.edu.cn
• Study Contact Backup: Name: Cheng-tao Wang; Phone Number: +862087755766; Email: ct_wang@163.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Recruiting
      • The First Affiliated Hospital of Sun Yat-sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1. Male or female, aged 18 to 75 years; 2. Performance status (PS) score ≤ 2 points; 3. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (RFS)	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.	3 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall-survival (OS)	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.	3 month
Adverse events rate	Adverse events during the treatment period using Common Terminology Criteria for Adverse Events (CTCAE) (version 5.0).	One month

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: Yong Chen, First Affiliated Hospital, Sun Yat-Sen University

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): August 1, 2020
• Primary Completion (ANTICIPATED): August 1, 2023
• Study Completion (ANTICIPATED): August 1, 2025

Study Registration Dates

• First Submitted: August 4, 2020
• First Submitted That Met QC Criteria: August 4, 2020
• First Posted (ACTUAL): August 6, 2020

Study Record Updates

• Last Update Posted (ACTUAL): August 6, 2020
• Last Update Submitted That Met QC Criteria: August 4, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: chemotherapy; radiotherapy; prognosis; hypopharyngeal carcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Carcinoma; Hypopharyngeal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel; Cisplatin; Fluorouracil
• Other Study ID Numbers: hypopharyngeal SCC 001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No