A Study of AT-101 in Combination With Docetaxel in Squamous Cell Carcinoma Of The Head and Neck
Condition: Squamous Cell Carcinoma of the Head and Neck (SCCHN)
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
Intervention: AT-101; Docetaxel
Intervention description: 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; Docetaxel 75 mg/m2 on Cycle Day 1
Intervention MeSH terms: Docetaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 35.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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?
    

Eligibility criteria:

        Inclusion Criteria:

          1. Males and non-pregnant, non-lactating females at least 18 years old.

          2. Histologically or cytologically confirmed diagnosis of SCCHN (Squamous Cell Carcinoma
             of the Head and Neck).

          3. Stage IVC (metastatic), or advanced, locally recurrent SCCHN not amenable to surgery
             or palliative radiotherapy.

          4. 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

          5. 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.

          6. ECOG performance status ≤ 1 (Appendix 2)

          7. Expected survival of at least 3 months

          8. 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

          9. Negative pregnancy test for females of childbearing potential

         10. 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

         11. 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

         12. Willingness and ability to comply with study procedures and follow-up examination

        Exclusion Criteria:

          1. Pregnant or nursing women.

          2. Prior docetaxel treatment for SCCHN in the metastatic setting.

          3. 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.

          4. 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.

          5. 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.

          6. 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.

          7. Any concurrent therapy intended to treat SCCHN.

          8. Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional
             Classification

          9. Symptomatic hypercalcemia or hypercalcemia that is > Grade 2.

         10. 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).

         11. 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).

         12. 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.

         13. Patients who are contraindicated for treatment with docetaxel.

         14. 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.

         15. 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.

         16. Prior use of gossypol or AT-101, or known hypersensitivity to gossypol or AT-101.

         17. 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.

         18. Any patient being treated for acute deep vein thrombosis or patients with a history of
             recurrent deep vein thrombosis independent of treatment with anticoagulation.

         19. Any other condition or circumstance that would, in the opinion of the Investigator,
             make the patient unsuitable for participation in the study.