Clinical trial NCT00982436: Neoadjuvant Cisplatin/Docetaxel (CDDP/TXT) and Chemoradiation for Head and Neck Cancer
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Head and Neck Neoplasms
Keywords: Combined Modality Therapy
Neoadjuvant Therapy
Head and neck neoplasms
Lead sponsor: University of Vermont
Sponsor class: OTHER
First posted: 2009-09-23
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Response rate to neoadjuvant chemotherapy with docetaxel/cisplatin, followed by chemoradiotherapy in locally advanced squamous head and neck cancer
timeFrame: 6 months after initiation of therapy
Secondary outcomes:
measure: Response rate to neoadjuvant chemotherapy with docetaxel/cisplatin in locally advanced squamous head and neck cancer
timeFrame: 3 months after initiation of therapy
measure: Response rate to chemoradiotherapy in locally advanced squamous head and neck cancer
timeFrame: 6 months after initiation of therapy
measure: Toxicity of neoadjuvant chemotherapy with docetaxel/cisplatin, followed by chemoradiotherapy in locally advanced squamous head and neck cancer
timeFrame: Every 3 weeks for 6 months (during therapy)
measure: Progression free survival after neoadjuvant chemotherapy with docetaxel/cisplatin, followed by chemoradiotherapy in locally advanced squamous head and neck cancer
timeFrame: Every 6 months
measure: Overall survival after neoadjuvant chemotherapy with docetaxel/cisplatin, followed by chemoradiotherapy in locally advanced squamous head and neck cancer
timeFrame: Every 6 months
Other outcomes:
Locations:
city: Berlin
country: United States
facility: Mountainview Medical Center
state: Vermont
city: Burlington
country: United States
facility: Fletcher Allen Health Care
state: Vermont
city: Colchester
country: United States
facility: Vermont Center for Cancer Medicine
state: Vermont
Study officials:
affiliation: University of Vermont/Feltcher Allen Health Care
name: Steven M Grunberg, MD
role: PRINCIPAL_INVESTIGATOR
References: