Induction Chemotherapy for Advanced Head and Neck Cancer

Head and Neck Cancer Clinical Trial

Official title:

Induction Chemotherapy (IC) With Paclitaxel and Cisplatin (PC) Followed by Concomitant Chemoradiotherapy (CCRT) in Patient With Advanced Squamous Carcinoma of the Head and Neck (SSCHN).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00959387
• Other study ID #: Barretos-01
• Status: Completed
• Phase: Phase 2
• First received: August 3, 2009
• Last updated: March 22, 2014
• Start date: August 2009
• Est. completion date: April 2013

Study information

• Verified date: March 2014
• Source: Barretos Cancer Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

Over the last 30 years, induction chemotherapy (IC) has become important for the management of patients with locally advanced HNSCC (LAHNSCC), particularly since the introduction of taxanes. The results reported in the TAX 323 and TAX 324 trials indicate that the TPF regimen (docetaxel, cisplatin and 5-fluorouracil) improves overall survival comparing with the PF regimen (cisplatin and 5-fluorouracil), and the TPF regimen is globally the most accepted induction regimen for the treatment of LAHNSCC.

However, the TPF regimen has been associated with high toxicity rates, and patients frequently decline cisplatin during concurrent radiotherapy and require the use of infusion pumps and a central venous catheter.

Extensive efforts are ongoing to identify alternative schemes that are less toxic than the TPF regimen but are as effective for LAHNSCC and safely allow the use of definitive concurrent treatment based on cisplatin and radiotherapy.

Description:

This non-randomized phase II trial evaluated the safety, feasibility and response rates of concurrent therapy (cisplatin and radiotherapy) after three cycles of an IC regimen based on the combination of cisplatin plus paclitaxel without 5-fluorouracil (5FU) (thereby avoiding infusion pumps and a central venous catheter) in LAHNSCC patients with a high tumor burden.

The patients were stratified by tumor subsite (oropharynx and hypopharynx/larynx) and by tumor resectable status (resectable or irresectable advanced squamous cell).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: April 2013
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 76 Years

Eligibility

Inclusion Criteria:

• Histologically confirmed locally advanced squamous cell carcinoma of head and neck (stage III and IV) eligible to chemoradiotherapy.

• Presence of measurable disease

• = 18 year

• ECOG performance status: 0-2

• Adequate bone marrow functions evidenced by: absolute neutrophil count = 1.5 x 109/L; platelet count = 100 x 109/L and hemoglobin = 90 g/L

• Adequate renal function.

• Adequate hepatic function.

• Patients or their legal representatives must be able to read, understand and provide written informed consent to participate in the study.

Exclusion Criteria:

• Any previous chemotherapy or radiotherapy

• Patients who have known hypersensitivity to paclitaxel or cisplatin

• Patients who are receiving concurrent investigational, biological or immune therapies

• Concomitant administration of high doses of systemic corticosteroids

• Known HIV or Hepatitis B or C (active, previously treated or both; testing is not required)

• Uncontrolled CNS disease (e.g., seizures not controlled with standard medical therapy)

• Clinically significant cardiovascular disease.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Head and Neck Cancer
• Head and Neck Neoplasms

Intervention

Drug:
• Induction TP chemotherapy
3 cycles of paclitaxel 175mg/m2 and cisplatin 80mg/m2 q3w. All patients received supportive care during radiotherapy, including dietary measures, local antiseptics and laser therapy as preventive and curative support for oral mucositis.

Radiation:
• Chemoradiotherapy (CRT)
Patients were treated with 2-dimensional radiation therapy planning (6MV photon beams). A combination of lateral-opposed portals, anterior and lateral wedged fields was used to treat the primary tumor and the lymph nodes. The primary tumor, macroscopically affected lymph nodes and bilateral cervical plus supraclavicular lymph chains were treated with five fractions of 2Gy per week for 5 weeks (up to a total of 50Gy). Gross tumor volume was defined as the primary gross tumor or involved node, and this measure was based on clinical, radiological and endoscopic examinations. An additional margin of 1.0cm was added to the GTV to create the CTV. A boost of five fractions of 2Gy per week for 2 additional weeks (up to a total dose of 70Gy) was prescribed to the CTV plus a margin of 1.0cm.

Locations

Country	Name	City	State
Brazil	Barretos Cancer Hospital	Barretos	São Paulo

Sponsors (1)

Lead Sponsor	Collaborator
Barretos Cancer Hospital

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tumor response rate	Tumor response was assessed after induction chemotherapy (just before chemoradiotherapy) and 6-8 weeks after completion of chemoradiotherapy.; Evaluation of tumor response was by clinical examination, nasoendoscopy, and CT or MRI imaging of the primary site and the neck (RECIST criteria 1.1).	At baseline, 2 weeks after the third cycle of IC and 6-8 weeks after the end of radiotherapy	Yes
Secondary	Overall survival	Overall survival (OS) was calculated as the time of study entry to the date of death.	3 years	Yes
Secondary	Quality of life (EORTC QLQ-C30)	Questionnaire of quality of life (EORTC QLQ-C30) was applied at baseline, before chemoradiotherapy and 60 days following last day of radiotherapy.	2 years	Yes
Secondary	Adverse Events rate	Adverse events were graded according to the expanded common toxicity criteria of the Clinical Trials Group of the National Cancer Institute of Canada (NCI CTCAE v3.0). Laboratory safety data were assessed before the administration of chemotherapy and after treatment.	After every cycle of IC, after every cycle of concurrent chemetherapy and up to 8 weeks after the end of radiotherapy	Yes
Secondary	Progression-free survival.	Progression-free survival (PFS) was calculated as the date of assignment to recurrence/progression or death resulting from any cause. If the patient had no evidence of the aforementioned events, survival was censored at the time of the last documented evaluation of efficacy/contact or death resulting from another cause.	3 years	Yes