Neoadjuvant Cisplatin/Docetaxel (CDDP/TXT) and Chemoradiation for Head and Neck Cancer

Head and Neck Neoplasms Clinical Trial

Official title:

A Pilot Study to Evaluate Response to Neoadjuvant Chemotherapy With Cisplatin and Docetaxel Followed by Chemoradiation Therapy With Carboplatin in Stage IV Non-metastatic Head and Neck Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00982436
• Other study ID #: VCC 0905
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: September 22, 2009
• Last updated: March 21, 2012
• Start date: September 2009
• Est. completion date: December 2012

Study information

• Verified date: March 2012
• Source: University of Vermont
• Contact: Steven M Grunberg, MD
• Phone: 802-847-8400
• Email: Steven.Grunberg[@]vtmednet.org
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the effectiveness and safety of neoadjuvant chemotherapy (chemotherapy given before radiotherapy) using cisplatin and docetaxel, followed by carboplatin given at the same time as radiotherapy in the treatment of locally advanced head and neck cancer.

Description:

Chemoradiotherapy has become the standard of care for patients with unresectable head and neck cancer, but there can be substantial added toxicity with chemoradiotherapy compared to radiation therapy alone. Neoadjuvant therapy with cisplatin / 5-fluorouracil has demonstrated activity in this disease, and taxanes appear to improve response further. Docetaxel / cisplatin / 5-fluorouracil has been shown to be a highly active regimen. However, with the potential added toxicities of neoadjuvant chemotherapy, it is important to minimize toxicity while maintaining efficacy. Chemotherapeutic agents that are DNA cycle-specific like 5-fluorouracil are more stomatotoxic than those that are cell phase non-specific. Of note, several studies have suggested that docetaxel and cisplatin is a highly active combination when used for advanced disease or as neoadjuvant therapy .

This study will therefore test the efficacy of neoadjuvant chemotherapy with cisplatin and docetaxel without 5-fluorouracil followed by chemoradiotherapy with carboplatin to determine whether promising response rates with modest toxicity can be achieved. Carboplatin will be used as the radiosensitizing agent during chemoradiotherapy to reduce nephrotoxicity and neurotoxicity as compared to further treatment with cisplatin.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 37
• Est. completion date: December 2012
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically proven locoregional Stage 4 squamous cell carcinoma of the oral cavity, larynx, oropharynx or hypopharynx

• Measurable or evaluable disease

• No distant metastases

• Tumor should be surgically unresectable for cure or resection is considered inadvisable

• Age > 18 years

• ECOG performance status 0, 1 or 2

• Life expectancy > 2 months

• Patients must have adequate organ and marrow function as defined below:

• Leukocytes > 3,000/mm3

• Absolute neutrophil count > 1,500/mm3

• Platelets > 100,000/mm3

• Hemoglobin > 10.0g/dL

• Total Bilirubin <= institutional upper limit of normal

• Aspartate aminotransferase < 2.5 X institutional upper limit of normal

• Alanine aminotransferase < 2.5 X institutional upper limit of normal

• Alkaline phosphatase < 2.5 X institutional upper limit of normal

• Creatinine <= institutional upper limit of normal OR creatinine clearance > 60 mL/min/1.73 m2 for patients with creatinine > institutional upper limit of normal

• Signed informed consent

• Women of child-bearing potential and men must be willing and able practice adequate contraception prior to study entry and for the duration of study treatment

Exclusion Criteria:

• Previous chemotherapy for this malignancy

• Previous radiotherapy to head and neck region

• Other malignancy within last 5 years except for non-melanoma skin cancer

• Uncontrolled intercurrent illness that would prevent delivery of protocol therapy

• Peripheral neuropathy > Grade 2

• Hypercalcemia

• Patient is pregnant or lactating

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 Neoplasms

Intervention

Drug:
• Docetaxel/cisplatin
Docetaxel 75 mg/m2 intravenous every 3 weeks for 3 cycles Cisplatin 75 mg/m2 intravenous every 3 weeks for 3 cycles

Radiation:
• Radiotherapy
70 Gy in 35 fractions to gross tumor and lymph node metastases

Drug:
• Carboplatin
Carboplatin AUC 1.5 intravenous weekly during radiotherapy

Locations

Country	Name	City	State
United States	Mountainview Medical Center	Berlin	Vermont
United States	Fletcher Allen Health Care	Burlington	Vermont
United States	Vermont Center for Cancer Medicine	Colchester	Vermont

Sponsors (1)

Lead Sponsor	Collaborator
University of Vermont

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rate to neoadjuvant chemotherapy with docetaxel/cisplatin, followed by chemoradiotherapy in locally advanced squamous head and neck cancer		6 months after initiation of therapy	No
Secondary	Response rate to neoadjuvant chemotherapy with docetaxel/cisplatin in locally advanced squamous head and neck cancer		3 months after initiation of therapy	No
Secondary	Response rate to chemoradiotherapy in locally advanced squamous head and neck cancer		6 months after initiation of therapy	No
Secondary	Toxicity of neoadjuvant chemotherapy with docetaxel/cisplatin, followed by chemoradiotherapy in locally advanced squamous head and neck cancer		Every 3 weeks for 6 months (during therapy)	Yes
Secondary	Progression free survival after neoadjuvant chemotherapy with docetaxel/cisplatin, followed by chemoradiotherapy in locally advanced squamous head and neck cancer		Every 6 months	No
Secondary	Overall survival after neoadjuvant chemotherapy with docetaxel/cisplatin, followed by chemoradiotherapy in locally advanced squamous head and neck cancer		Every 6 months	No