Clinical trial NCT03815903: Induction Chemotherapy for Locally Advanced Head and Neck Squamous Cell Carcinoma
Official title: A Phase 3, Randomized, Open-label Clinical Trial of Induction Chemotherapy Followed by Chemoradiotherapy Versus Chemoradiotherapy in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Locally Advanced Malignant Neoplasm
Lead sponsor: Barretos Cancer Hospital
Sponsor class: OTHER
First posted: 2019-01-24
Enrollment: 434
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The benefit of induction chemotherapy followed by chemoradiotherapy for locally advanced head and neck squamous cell carcinoma is unknown. The present study is investigating if this therapeutic strategy improve overall survival.


Eligibility criteria: Inclusion Criteria:

* Confirmed histological diagnosis of squamous cell carcinoma or undifferentiated carcinoma of the oropharynx, hypopharynx or larynx;
* Locally advanced stage (stage IVa / b - AJCC 8th edition), classified as resectable \*\* or unresectable and candidate for treatment based on radiotherapy and chemotherapy;
* Locally advanced stage (stage III - AJCC 8th edition), classified as resectable or unresectable, positive p16 and candidate for treatment based on radiotherapy and chemotherapy;
* It will be allowed to include a patient with cervical lymphadenectomy if the primary lesion is measurable;
* Presence of measurable disease according to RECIST 1.1 criteria;
* ECOG performance status of 0-1;
* ≥ 18 years;
* Adequate marrow reserve indicated by:

  * Absolute neutrophil count (ANC) ≥ 1500 / mm³ or Platelets\> 100,000 / mm³
  * Hemoglobin ≥ 9 g / dL - red blood cell transfusion will be allowed in the screening period if necessary
* Adequate renal and hepatic function:

  * Serum bilirubin ≤ 1.5 times the upper limit of normal the TGO and TGP ≤ 3 upper limit of normal. If hepatic metastasis ≤ 5 upper limit of normal
  * Serum creatinine ≤ 1.5 mg / dL and creatinine clearance ≥ 60 mL / min calculated by Cockcroft-Gault.

Exclusion Criteria:

* Patient submitted to curative resection of the primary site and / or metastatic site. NOTE: Patients submitted to cervical lymphadenectomy without surgery to the primary tumor are eligible;
* Radiation therapy or previous chemotherapy for head / neck tumor;
* Patients with occult primary tumor;
* T4 from any site, resectable, with invasion of cartilage or jaw;
* History of BMT or stem cell therapy;
* Synchronous tumor or previous history of neoplasia, except for in situ carcinoma of the cervix, basal cell carcinoma or epidermoid carcinoma. Patients with previous history of cancer already treated and without evidence of disease for more than 3 years may participate in the study;
* Prophylactic use of G-CSF or GM-CSF two weeks prior to the study;
* Clinically significant heart disease: unstable angina or myocardial infarction 6 months prior to study entry Symptomatic ventricular arrhythmia the ICC classified as NYHA ≥ II • Uncontrolled hypercalcemia;
* Uncontrolled infection;
* Any other comorbidity that the investigator's judgment is inappropriate for the study;
* Peripheral neuropathy\> grade 2;
* Hearing loss\> grade 2;
* Known positive serology for hepatitis B, hepatitis C or HIV
* Use of antiretrovirals;

Primary outcomes:
measure: 3-years overall survival
timeFrame: From date of randomization until 3 years
Secondary outcomes:
measure: Progression free survival
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
measure: Systemic relapse free survival
timeFrame: From date of randomization until the date of first systemic relapse or date of death from any cause, whichever came first, assessed up to 100 months
measure: Overall survival
timeFrame: From date of randomization until the date of death from any cause, whichever came first, assessed up to 100 months
measure: Overall response rate
timeFrame: At the end of Cycle 3 of IC (each cycle is 21 days) and 8 weeks after the end of radiotherapy, through study completion, an average of 6 months
measure: Adverse Events Rates
timeFrame: At the end of cycle 1, cycle 2 and cycle 3 (each cycle is 21 days).
measure: 1-year functional organ preservation rate
timeFrame: From date of randomization until 1 year after
measure: Quality of Life (EORTC Quality of Life Questionnare - C30 version 3.0)
timeFrame: From date of randomization until 5 years
measure: Overall response rate to induction chemotherapy
timeFrame: At the end of Cycle 3 (each cycle is 21 days)
Other outcomes:
Locations:
city: Barretos
country: Brazil
facility: Barretos Cancer Hospital
state: São Paulo
Study officials:
References: