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

Phase 1

• Conditions: Head and Neck Neoplasms
• Interventions: Drug: Docetaxel/cisplatin; Radiation: Radiotherapy; Drug: Carboplatin

• Registration Number: NCT00982436
• Lead Sponsor: University of Vermont

Brief 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.

Detailed 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.

Study Timeline

• Study Start: 2009-09
• Study First Submitted: 2009-09-22
• Study First Submitted QC: 2009-09-22
• Study First Posted: 2009-09-23
• Status Verified: 2012-03
• Last Update Submitted: 2012-03-21
• Last Update Posted: 2012-03-22
• Primary Completion: 2012-09
• Study Completion: 2012-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 37

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Neoadjuvant/Concomitant Chemoradiation	Docetaxel/cisplatin	Three cycles of docetaxel/carboplatin neoadjuvant chemotherapy followed by chemoradiotherapy for 7 weeks with weekly carboplatin
Neoadjuvant/Concomitant Chemoradiation	Radiotherapy	Three cycles of docetaxel/carboplatin neoadjuvant chemotherapy followed by chemoradiotherapy for 7 weeks with weekly carboplatin
Neoadjuvant/Concomitant Chemoradiation	Carboplatin	Three cycles of docetaxel/carboplatin neoadjuvant chemotherapy followed by chemoradiotherapy for 7 weeks with weekly carboplatin

Primary Outcome Measures

Name	Time	Method
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

Secondary Outcome Measures

Name	Time	Method
Response rate to neoadjuvant chemotherapy with docetaxel/cisplatin in locally advanced squamous head and neck cancer	3 months after initiation of therapy
Response rate to chemoradiotherapy in locally advanced squamous head and neck cancer	6 months after initiation of therapy
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)
Progression free survival after neoadjuvant chemotherapy with docetaxel/cisplatin, followed by chemoradiotherapy in locally advanced squamous head and neck cancer	Every 6 months
Overall survival after neoadjuvant chemotherapy with docetaxel/cisplatin, followed by chemoradiotherapy in locally advanced squamous head and neck cancer	Every 6 months

Trial Locations

Locations (3)

Fletcher Allen Health Care; 🇺🇸 Burlington, Vermont, United States

Vermont Center for Cancer Medicine; 🇺🇸 Colchester, Vermont, United States

Mountainview Medical Center; 🇺🇸 Berlin, Vermont, United States