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

This study has suspended participant recruitment.
(drug potency expiration and sponsor inability to manufacture more drug)
Sponsor:
Information provided by (Responsible Party):
Francis (Frank) Worden, University of Michigan Cancer Center
ClinicalTrials.gov Identifier:
NCT01285635
First received: January 20, 2011
Last updated: June 21, 2013
Last verified: March 2013
  Purpose

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?


Condition Intervention Phase
Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Drug: AT-101
Drug: Docetaxel
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by University of Michigan Cancer Center:

Primary Outcome Measures:
  • Proportion of patients with a complete response, partial response, objective response, and clinical benefit as a measure of efficacy [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    To estimate the proportion of patients with a complete response (CR), partial response(PR), objective response (CR + PR), and clinical benefit (CR + PR + stable disease [SD]); to estimate the time to response and duration of response in responding patients.


Secondary Outcome Measures:
  • Median time to progression of disease as a measure of efficacy [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    To measure the median time to progression of disease and overall survival in patients with advanced, locally recurrent, or metastatic SCCHN

  • Measure the grade III/IV toxicities for safety and tolerability [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
    To measure the grade III/IV toxicities experienced by patients with advanced, locally recurrent, or metastatic SCCHN

  • Quality of Life measures [ Time Frame: see description below ] [ Designated as safety issue: No ]
    To compare the quality of life of head and neck cancer patients undergoing differing palliative treatment protocols as long as the patient receives care at our institution


Estimated Enrollment: 25
Study Start Date: June 2010
Estimated Study Completion Date: January 2014
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Docetaxel Alone Drug: Docetaxel
Docetaxel 75 mg/m2 on Cycle Day 1
Experimental: Pulse Dose AT-101 Arm Drug: AT-101
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
Drug: Docetaxel
Docetaxel 75 mg/m2 on Cycle Day 1
Experimental: Metronomic AT-101 Arm Drug: AT-101
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
Drug: Docetaxel
Docetaxel 75 mg/m2 on Cycle Day 1

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01285635

Locations
United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
Sponsors and Collaborators
University of Michigan Cancer Center
Investigators
Principal Investigator: Francis Worden, MD University of Michigan Cancer Center
  More Information

No publications provided

Responsible Party: Francis (Frank) Worden, Associate Professor of Internal Medicine, University of Michigan Cancer Center
ClinicalTrials.gov Identifier: NCT01285635     History of Changes
Other Study ID Numbers: UMCC 2010.031, HUM00040432
Study First Received: January 20, 2011
Last Updated: June 21, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Gossypol
Gossypol acetic acid
Docetaxel
Contraceptive Agents, Male
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Contraceptive Agents, Female
Spermatocidal Agents
Antispermatogenic Agents

ClinicalTrials.gov processed this record on April 17, 2014