A Study of AT-101 in Combination With Docetaxel in Squamous Cell Carcinoma Of The Head and Neck

Study Overview
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Brief Summary
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This study will examine the effects of an investigational drug called AT-101 in combination with an FDA approved cancer drug called Docetaxel. It is hoped that AT-101 will help the Docetaxel to have a better effect in slowing or stopping cancer cell growth. This study will help the researchers learn what effects, if any, the combination of AT-101 and Docetaxel has on your cancer. For instance, will the combination cause your tumor(s) to shrink or stop growing? The researchers will also learn about the safety of the combination of AT-101 and Docetaxel. For instance, are there any side effects? If so, what kind of side effects does the combination cause? How severe are the side effects, and how often do they occur?

Official Title
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A Phase II of AT-101 in Combination With Docetaxel in Patients With Recurrent, Locally Advanced or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Conditions
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Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Intervention / Treatment
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* Drug: AT-101
* Drug: Docetaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and non-pregnant, non-lactating females at least 18 years old. Histologically or cytologically confirmed diagnosis of SCCHN (Squamous Cell Carcinoma of the Head and Neck). Stage IVC (metastatic), or advanced, locally recurrent SCCHN not amenable to surgery or palliative radiotherapy. Presence of measurable disease as defined by RECIST (Response Evaluation Criteria in Solid Tumors) a. If the only site of measurable disease for this study is within a prior field of irradiation, then the sum of the longest diameter (SLD) of that lesion must have increased by at least 20% from the prior treatment nadir Received no more than two prior systemic chemotherapeutic regimen for SCHNN in the locally advanced or metastatic setting and have relapsed after or be refractory to therapy Systemic therapies given in the adjuvant setting or with chemoradiotherapy are counted only if the patient relapses after 6 months of the last cycle of chemotherapy or the completion of radiation Included as systemic chemotherapy regimens (but not limited to) are patients who may have received erlotinib (Tarceva®) or another EGFR inhibitor. Previous treatment with paclitaxel (but not docetaxel) is permitted. ECOG performance status ≤ 1 (Appendix 2) Expected survival of at least 3 months Adequate liver and renal and bone marrow function as indicated by: Serum creatinine ≤ 2.0 times the upper limit of normal, AND Serum albumin ≥ 3.0 gm/dL, AND Total bilirubin ≤ 1.0 times the upper limit of normal, AND Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) ≤ 2.5 times the upper limit of normal (ULN) for the testing laboratory. Note: For patients with alkaline phosphatase ≥ 2.5 x ULN, the AST and ALT must be ≤ 1.5 x ULN Hemoglobin ≥ 9 g/dL (may be post-transfusion); Platelet count ≥ 100 x103 cells/mm3 Neutrophil count ≥1500 cells/mm3 Negative pregnancy test for females of childbearing potential Willingness to use contraception by a method that is deemed effective by the Investigator by both males and female patients of childbearing potential (postmenopausal women must have been amenorrheal for at least 12 months to be considered of non-childbearing potential) and their partners throughout the treatment period and for at least 30 days following the last dose of AT-101 Ability to understand and the willingness to sign a written informed consent form; the consent form must be signed by the patient prior to any study-specific procedures Willingness and ability to comply with study procedures and follow-up examination Exclusion Criteria: Pregnant or nursing women. Prior docetaxel treatment for SCCHN in the metastatic setting. Treatment of SCCHN with chemotherapy within 28 days of the first dose of study treatment. Acute toxicities from prior therapy must have resolved to Grade ≤ 1. Patients whose disease responded to the most recently administered prior regimen must have documented progression of disease subsequent to that regimen, to be eligible. Treatment with monoclonal antibody (e.g., VEGF or EGFR targeting antibody) within 45 days prior to the first dose of study treatment. Acute toxicities from prior therapy must have resolved to Grade ≤ 1. Patients whose disease responded to the most recently administered prior regimen must have documented progression of disease subsequent to that regimen, to be eligible. Treatment of SCCHN with radiotherapy within 14 days of the first dose of study treatment. Prior radiotherapy is permissible only if the lesions used for determination of disease activity (i.e., target lesions) were not previously irradiated, or have increased in size since the completion of radiotherapy, and the patient has fully recovered from any toxicity of the radiotherapy. Treatment of SCCHN with erlotinib within 14 days of the first dose of study treatment. Acute toxicities from prior therapy must have resolved to Grade ≤ 1. Patients whose disease responded to the most recently administered prior regimen must have documented progression of disease subsequent to that regimen, to be eligible. Any concurrent therapy intended to treat SCCHN. Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification Symptomatic hypercalcemia or hypercalcemia that is > Grade 2. Participation in any investigational drug study within 28 days prior to study treatment. (Patient must have recovered from all acute effects of previously administered investigational agents). Active secondary malignancy or history of other malignancy within the last five years (patients who have been disease-free for five years, or have a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible). Active symptomatic fungal, bacterial and/or viral infection including active HIV. Note: protocol does not require screening for viruses; however, patients with known active infections are excluded. Patients who are contraindicated for treatment with docetaxel. Have malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, ulcerative colitis, inflammatory bowel disease, partial or complete small bowel obstruction. Uncontrolled CNS (Central Nervous System) metastases. Patients with known, previously treated CNS metastases are eligible if they are neurologically stable, as per the investigating physician's clinical assessment, and do not require steroids at the time of study entry. Prior use of gossypol or AT-101, or known hypersensitivity to gossypol or AT-101. Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Any patient being treated for acute deep vein thrombosis or patients with a history of recurrent deep vein thrombosis independent of treatment with anticoagulation. Any other condition or circumstance that would, in the opinion of the Investigator, make the patient unsuitable for participation in the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Docetaxel Alone<br> | Drug: Docetaxel<br>* Docetaxel 75 mg/m2 on Cycle Day 1<br>|
| Experimental: Pulse Dose AT-101 Arm<br> | Drug: AT-101<br>* Pulse Dose: AT-101 dose of 40 mg b.i.d. on days 1-3 Metronomic Dose: AT-101, 20 mg daily, days 1-14<br>Drug: Docetaxel<br>* Docetaxel 75 mg/m2 on Cycle Day 1<br>|
| Experimental: Metronomic AT-101 Arm<br> | Drug: AT-101<br>* Pulse Dose: AT-101 dose of 40 mg b.i.d. on days 1-3 Metronomic Dose: AT-101, 20 mg daily, days 1-14<br>Drug: Docetaxel<br>* Docetaxel 75 mg/m2 on Cycle Day 1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With a Complete Response (CR) and Partial Response (PR) | The primary objective is to estimate the proportion of patients with a complete response (CR) and partial response(PR) defined by RECIST (Response Evaluation Criteria in Solid Tumors). CR is defined as the disappearance of all target lesions and PR is defined as at least a 20% decrease in the sum of the longest diameter of target lesions. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Duration of Response For All Groups Combined |  | 3 years | 
| Incidence of Grade 3 and 4 Toxicities by Arm | Measure the grade III/IV toxicities experienced by patients with advanced, locally recurrent, or metastatic SCCHN | 3 years | 
| Median Overall Survival in Months |  | 3 Years | 
| Median Progression Free Survival in Months | Progression is defined, by RECIST (Response Evaluation Criteria in Solid Tumors), as at least a 20% increase in the sum of the longest diameter of target lesions. | 3 Years |