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

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

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.

Study Overview

• Status: Unknown
• Conditions: Head and Neck Neoplasms
• Intervention / Treatment: Drug: Docetaxel/cisplatin; Radiation: Radiotherapy; Drug: Carboplatin

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 Type: Interventional
• Enrollment (Anticipated): 37
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Steven M Grunberg, MD; Phone Number: 802-847-8400; Email: Steven.Grunberg@vtmednet.org
• Study Contact Backup: Name: Madhuri V Vithala, MD; Phone Number: 802-847-8400; Email: Madhuri.Vithala@vtmednet.org

Study Locations

• United States
  • Vermont
    • Berlin, Vermont, United States, 05602
      • Recruiting
      • Mountainview Medical Center
      • Contact: John Valentine, MD; Phone Number: 802-225-5400; Email: john.valentine@cvmc.org
      • Principal Investigator: John Valentine, MD
      • Sub-Investigator: David Ospina, MD
      • Sub-Investigator: Daniel Fram, MD
    • Burlington, Vermont, United States, 05401
      • Recruiting
      • Fletcher Allen Health Care
      • Principal Investigator: Steven M Grunberg, MD
      • Contact: Madhuri V Vithala, MD; Phone Number: 802-847-8400; Email: Madhuri.Vithala@vtmednet.org
      • Contact: Steven Grunberg, MD; Phone Number: 802-847-8400; Email: Steven.Grunberg@vtmednet.org
      • Sub-Investigator: Madhuri V Vithala, MD
      • Sub-Investigator: Havaleh Gagne, MD
      • Sub-Investigator: William Brundage, MD
    • Colchester, Vermont, United States, 05446
      • Recruiting
      • Vermont Center for Cancer Medicine
      • Sub-Investigator: Christian Thomas, MD
      • Sub-Investigator: Paul Unger, MD
      • Sub-Investigator: Dennis Sanders, MD
      • Sub-Investigator: Johannes Nunnink, MD
      • Contact: Christian Thomas, MD; Phone Number: 802-655-3400; Email: Christian.Thomas@vtmednet.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Neoadjuvant/Concomitant Chemoradiation; Three cycles of docetaxel/carboplatin neoadjuvant chemotherapy followed by chemoradiotherapy for 7 weeks with weekly carboplatin

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; Other Names: Taxotere; Platinol; Radiation: Radiotherapy; 70 Gy in 35 fractions to gross tumor and lymph node metastases; Other Names: Radiation therapy; Drug: Carboplatin; Carboplatin AUC 1.5 intravenous weekly during radiotherapy; Other Names: Paraplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: University of Vermont
• Investigators: Principal Investigator: Steven M Grunberg, MD, University of Vermont/Feltcher Allen Health Care

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Anticipated): September 1, 2012
• Study Completion (Anticipated): December 1, 2012

Study Registration Dates

• First Submitted: September 22, 2009
• First Submitted That Met QC Criteria: September 22, 2009
• First Posted (Estimate): September 23, 2009

Study Record Updates

• Last Update Posted (Estimate): March 22, 2012
• Last Update Submitted That Met QC Criteria: March 21, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: Neoadjuvant Therapy; Combined Modality Therapy; Head and neck neoplasms
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel; Carboplatin; Cisplatin
• Other Study ID Numbers: VCC 0905