Clinical trial NCT00570674: Abraxane in Combination With Carboplatin, Erbitux and IMRT for Locally Advanced Squamous Cancer of the Head and Neck
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Squamous Cell Carcinoma of the Head and Neck
Basaloid Squamous Cell Carcinoma
Undifferentiated Carcinoma
Adenosquamous Cell Carcinoma
Keywords: SSCHN
Abraxane
IMRT
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: Celgene Corporation
First posted: 2007-12-11
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically proven squamous cell carcinoma of th head and neck or its variants. Primary tumor sites eligible include nasopharynx, oral cavity, oropharynx, hypopharynx, larynx, or unknown primary SSCHN. Although they have squamous histology, tumors of the skin, nasal cavity and paranasal sinuses are excluded because their responsiveness to chemotherapy and radiotherapy may differ.
* Stage III or IV disease, without evidence of distant metastasis, according to the American Joint Committee on Cancer.
* Measurable disease, according to RECIST.
* Treatment-naive SSCHN, i.e. no prior chemotherapy, radiotherapy or attempted complete resection.
* \< CTCAE v3.0 Grade 2 neuropathy
* 18 years of age or older
* ECOG Performance Status of 0 or 1
* No active alcohol addiction or other condition that, in the opinion of the study investigators, would interfere with the subject's ability to comply with the treatment plan.
* Lab values as outlined in the protocol
* Negative pregnancy test within 7 days of study entry

Exclusion Criteria:

* Pregnant or breast-feeding women, or women and men of childbearing potential not willing to use adequate contraception while receiving treatment and for at least 6 months thereafter.
* Symptomatic peripheral neuropathy Grade 2 or greater by CTCAE v3.0
* History of other malignancy within the previous 5 years, except for non-melanoma skin cancer, carcinoma in situ of the cervix, bladder or head and neck.
* Prior therapeutic radiation to the head and neck
* Other serious illness or medical conditions, including but not limited to: unstable cardiac disease or myocardial infarction within 6 months prior to study entry; history of significant neurologic disorder, including advanced dementia or uncontrolled seizure disorder; clinically significant uncontrolled infection; active peptic ulcer disease defined as unhealed or clinically active ulcer; hypercalcemia; active drug addiction including cocaine or intravenous drug use, defined as occuring within 6 months preceding diagnosis; chronic obstructive pulmonary disease; autoimmune disease requiring active therapy; severe psoriasis; chronic uncontrolled diarrhea.
* Patients who experienced involuntary weight loss of more than 20% of their body weight in the two months preceding study entry
* Concurrent treatment with any other anticancer therapy
* Prior therapy that targets the EGFR pathway
* Participation in an investigational drug trial within 30 days of study entry

Primary outcomes:
measure: Abraxane Maximum Tolerated Dose (MTD) [Phase I]
timeFrame: Adverse event assessments occurred weekly on treatment; The observation period for MTD evaluation incorporated the 7 weeks of treatment.
measure: Dose Limiting Toxicity (DLT) [Phase I]
timeFrame: Adverse event assessments occurred weekly on treatment; The observation period for DLT evaluation incorporated the 7 weeks of treatment.
measure: 2-Year Disease-Free Survival [Phase II]
timeFrame: 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.
Secondary outcomes:
measure: Overall Response Rate [Phase I]
timeFrame: 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).
measure: 2-Year Overall Survival [Phase I]
timeFrame: 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.
measure: Duration PEG Therapy
timeFrame: Assessed until time of PEG removal which was up to 18.4 months in this study cohort.
measure: Change in FACT-H&N Score From Baseline to 4 Months
timeFrame: baseline and 4 months
measure: Change in FACT-H&N Score From Baseline to 6 Months
timeFrame: Baseline and 6 months
measure: Change in FACT-H&N Score From Baseline to 12 Months
timeFrame: Baseline and 12 months
measure: Change in FACT-H&N Score From Baseline to 24 Months
timeFrame: Baseline and 24 months
Other outcomes:
Locations:
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Roy B. Tishler, MD
role: PRINCIPAL_INVESTIGATOR
References: