Clinical Trial: Abraxane in Combination With Carboplatin, Erbitux and IMRT for Locally Advanced Squamous Cancer of the Head and Neck
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: A Phase I/II Trial of Abraxane in Combination With Carboplatin, Erbitux and Intensity Modulated Radiation Therapy (IMRT)for Treatment of Locally Advanced Squamous Cancer of the Head and Neck
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 Summary:
Primary Objectives
- Phase I—To identify the maximally tolerated dose (MTD) of Abraxane given with carboplatin plus concurrent IMRT (AC-RT)
- Phase II—To evaluate efficacy in the phase II portion of the study by evaluating 2-year disease-free survival
Secondary Objectives
- To evaluate the safety and tolerability
- To estimate the overall response rate
- To estimate 2-year overall survival
- 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).
Sponsor: Dana-Farber Cancer Institute
Current Primary Outcome:
- Abraxane Maximum Tolerated Dose (MTD) [Phase I] [ Time Frame: Adverse event assessments occurred weekly on treatment; The observation period for MTD evaluation incorporated the 7 weeks of treatment. ]The Abraxane MTD in combination with carboplatin and concurrent IMRT is determined by the number of participants who experience a dose limiting toxicity (DLT). See subsequent primary outcome measure for the DLT definition. The MTD is defined as the highest dose at which fewer than one-third of participants experience a DLT. If no DLTs are observed then the MTD is not reached but the highest dose may then be the recommended phase II dose.
- Dose Limiting Toxicity (DLT) [Phase I] [ Time Frame: Adverse event assessments occurred weekly on treatment; The observation period for DLT evaluation incorporated the 7 weeks of treatment. ]Dose limiting toxicities (DLT) were defined as treatment-related: 1) grade 3-4 non-hematological toxicity excluding untreated nausea, vomiting and diarrhea; dysphagia, esophagitis, mucositis/stomatitis, dermatitis/rash, 2) Grade 3 or greater febrile neutropenia occurring during chemoradiotherapy, 3) Grade 4 neutropenia lasting >/= 7 days and 4) Grade 3 thrombocytopenia. Grade 4 toxicities resulting in a treatment breaks > 7 days were considered DLTs.
- 2-Year Disease-Free Survival [Phase II] [ Time Frame: Disease assessments occurred 8-10 weeks following treatment end then every 4-6 weeks (yr 1), every 8-10 weeks (yr 2), quarterly (yr 3) and semiannually up to 2 yrs since last pt enrolled. ]Disease-free survival (DFS) is defined as the time from registration to the earlier of disease recurrence or death
Original Primary Outcome:
- Phase I: To identify the maximally tolerated dose of Abraxane given with carboplatin and Erbitux plus concurrent IMRT. [ Time Frame: 2 years ]
- Phase II: To evaluate the efficacy by evaluating 2-year-disease-free survival. [ Time Frame: 2 years ]
Current Secondary Outcome:
- Overall Response Rate [Phase I] [ Time Frame: The primary re-staging assessment for response occurred 8-10 weeks following completion of treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1). ]Overall response (OR) rate was defined as achieving partial response (PR) or complete response (CR) based on RECIST 1.0 criteria on treatment. Per RECIST 1.0 for target lesions, CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. To be assigned a status of CR or PR, changes in tumor measurements must be confirmed by repeat assessments performed no fewer than 4 weeks after the response criteria are first met. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
- 2-Year Overall Survival [Phase I] [ Time Frame: All patients were followed for survival for a minimum of 2 years. Median survival follow-up was 44.7 months (range 10-70) in this study cohort. ]2-year overall survival is the proportion of patients alive at 2-years from study entry.
Original Secondary Outcome:
- To evaluate the safety and tolerability of the combination of Abraxane, carboplatin and Erbitux. [ Time Frame: 2 years ]
- To estimate the overall response rate to ACE-RT. [ Time Frame: 2 years ]
- To estimate 2-year overall survival. [ Time Frame: 2 years ]
- To evaluate functional outcome at 2 years with respect to speech, swallowing and overall quality of life. [ Time Frame: 2 years ]
Information By: Dana-Farber Cancer Institute
Dates:
Date Received: December 10, 2007
Date Started: November 2007
Date Completion:
Last Updated: October 18, 2016
Last Verified: October 2016
