Clinical trial NCT00570674
Conditions: Squamous Cell Carcinoma of the Head and Neck Basaloid Squamous Cell Carcinoma Undifferentiated Carcinoma Adenosquamous Cell Carcinoma
Keywords: SSCHN Abraxane IMRT
Sponsor: Dana-Farber Cancer Institute
Start date: 2007-11-01; Completion date: 2013-10-01
Enrollment: 29 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of the Phase I part of this research study is to determine the safest and most effective dose of Abraxane when given in combination with carboplatin and Erbitux during radiation therapy for head and neck cancer. The purpose of the Phase II part of this study is to determine the effects of the treatment on head and neck cancers, as well as to further study the safety of this treatment.

Detailed description:
Primary Objectives

1. Phase I-To identify the maximally tolerated dose (MTD) of Abraxane given with carboplatin plus concurrent IMRT (AC-RT)
2. Phase II-To evaluate efficacy in the phase II portion of the study by evaluating 2-year disease-free survival

Secondary Objectives

1. To evaluate the safety and tolerability
2. To estimate the overall response rate
3. To estimate 2-year overall survival
4. To evaluate functional outcome at 2 years with respect to speech, swallowing and overall quality of life (QoL), by determining mean duration of PEG-dependence and change in FACT-HN scores from baseline to 3, 6, 12 and 24 months.

STATISTICAL DESIGN:

The Phase I study followed a standard 3+3 dose escalation design. Four potential dose levels of Abraxane ultimately were under evaluation including a de-escalation dose level -1. \[Note: Erbitux was originally planned to be given with carboplatin and Abraxane, but removed due to toxicity experienced at dose level 1.\] The DLT observation period is the 7 weeks of treatment. The Phase I incorporated a10-patient expansion cohort to ensure that the toxicity at the MTD for AC-RT was acceptable. Planned enrollment for the Phase II study was 34 patients primarily to test whether 2-year disease-free survival was consistent with 75% rate as opposed to the null hypothesis of 53.5% based on prior research (RTOG 99-14).

Arms: arm 1: Phase I Dose Level 1 participants received Abraxane 20mg/m2 IV then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. One dose (400 mg/m2 IV) of Erbitux was given prior to start of radiation, then weekly at 250 mg/m2 IV. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions. arm 2: Phase I Dose Level -1 participants received Abraxane 20mg/m2 IV then carboplatin AUC 1.5 weekly IV during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions. arm 3: Phase I Dose Level 2 participants received Abraxane 30mg/m2 IV then carboplatin AUC 1.5 weekly IV during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions. arm 4: Phase I Dose Level 3 participants received Abraxane 40mg/m2 IV then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions. arm 5: Phase I Dose Level 4 participants received Abraxane 50mg/m2 IV then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.
Interventions: intervention 1: Abraxane intervention 2: Erbitux intervention 3: Carboplatin intervention 4: Intensity Modulated Radiation Therapy
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None intervention 4: None

Protocol documents: