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Study Summary
No. 2006-1050:.......Esophageal......Jaffer Ajani......Gastrointestinal Medical Oncology
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Study Summary Title
Study Summary
Number:
2006-1050
Study Title:An Open-label, Single-center, Phase 1/ 2 Study of Chemoradiotherapy and AT-101 in Patients with Locally Advanced Esophageal or Gastroesophageal Junction Cancer (AT-101-CS-102)
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Physician New Patient Referral
Name:Jaffer AjaniPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Gastrointestinal Medical OncologyReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-2828
Contact us about clinical trials
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General Information
Disease Group:EsophagealSupported By:Ascenta Therapeutics, Inc.
Phase of Study:Phase I/Phase IIReturn
Visit:
Monday to Friday for the first 5 to 6 weeks of treatment. Five to 6 weeks after
completion of treatment, esophagectomy and lymph node resection will be
performed.
Treatment
Agents:
5-FU
AT-101
Docetaxel
Radiation
Home Care:NA
Treatment Loc:Only at MDACC
Estimated
Length of Stay
in Houston:
NA
Description/
Intervention:
The goal of this clinical research study is to find the highest tolerable dose
of AT-101 that can be given in combination with radiotherapy and chemotherapy
(5-FU [5-fluorouracil] and docetaxel) to treat patients with esophageal or
gastroesophogeal junction cancer. The safety of AT-101 and the ability of the
drug to control the disease will also be studied.
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Study Objectives / Outcomes

Primary:

Phase 1: Assess the safety and tolerability of AT-101 in combination with chemoradiotherapy, and determine a recommended Phase 2 dose for the chemoradiotherapy combination.

Phase 2: Determine the pathologic complete response (pathCR) rate and to correlate tumor biomarker expression with clinical response in patients with resectable esophageal or gastroesophageal junction cancer treated with preoperative chemoradiotherapy and AT-101.

Secondary:

To assess the safety and toxicity of chemoradiotherapy and AT-101 in patients with esophageal or gastroesophageal junction cancer.

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Study Status Information
Study Activation / Registration Date:08/06/2007
IRB Review and Approval Date:08/06/2007
Study Type:Phase Ii Or Phase I/Ii
Recruitment Status:Terminated
Projected Accrual:N/A
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) Male or female patients age =/> 18 years.

2) Histologically confirmed primary (non-recurrent) adenocarcinoma (AC) or squamous cell carcinoma of the esophagus or AC of the gastroesophageal (GE) junction.

3) For Phase 1: Phase 1 patients must have unresectable disease (Stage II to IVb). A patient can be unresectable for medical reasons or technical reasons but eligible for chemoradiation.

4) For Phase 2: Phase 2 patients must have resectable cancer defined as: T2, T3, N0; OR T1-3, N+.

5) Patients with involvement of celiac nodes are eligible if the primary lesion is mid-thoracic, distal esophagus, or GE junction.

6) Bulk of tumor must involve the esophagus or GE junction if tumor extends below the GE junction into the proximal stomach.

7) Patients must have archived tumor tissue available to correlate tumor biomarker expression with clinical response. Availability of tumor specimens in paraffin blocks or at least two unstained slides must be confirmed prior to study entry. Results will not be used to determine patient eligibility for the study.

8) ECOG performance status 0-1.

9) Adequate hematologic function as indicated by: a) ANC =/>1.5 x 10^9/L; b) Hemoglobin =/>9.5 g/dL; c) Platelet count =/>100 x 10^9/L

10) Adequate liver and renal function as indicated by: a) Serum creatinine =/<1.5 mg/L x ULN or creatinine clearance of =/>60 cc/min; b) Total bilirubin =/<1.5 x ULN; c) AST and ALT =/<1.5 x ULN concomitant with alkaline phosphatase =/<2.5 x ULN

11) Pre-entry CT scans or MRI of the chest and abdomen are required. An imaging study suspicious for liver metastases must be followed with a negative liver biopsy before a patient can be considered to enter the study.

12) Ability to swallow and retain oral medication.

13) Ability to understand and willingness to sign a written informed consent form; the consent form must be signed by the patient prior to any study-specific procedures.

14) Willingness and ability to comply with study procedures and follow-up examination.

Exclusion Criteria:1) Patients with T1, N0 and inoperable T4 (unequivocal organ involvement). Inoperable T4 lesions are permitted in the Phase 1 portion of the study but not Phase 2.

2) Patients with distant metastasis, including M1b lymph node status (M1b status allowed on Phase I only for patients appropriate for chemoradiation). Lymph nodes suspicious of M1b status by CT scan must be verified by fine-needle aspiration cytology.(Phase 2 only)

3) Patients with a TE fistula or direct invasion into the mucosa of the trachea or major bronchi. Bronchoscopy (with biopsy and cytology if lesion is seen) is required, to exclude TE fistula if the primary carcinoma is <26 cm from the incisors. Bronchoscopy is also required when the cancer is at or above the carina by an imaging study.

4) For Phase 2: Patients with positive pleural, pericardial, or peritoneal cytology.

5) For Phase 2: Patients with carcinoma of the cervical esophagus.

6) For Phase 2: Patients with clinical evidence of metastasis to cervical or supraclavicular lymph nodes.

7) For Phase 2: Patients with multiple primary carcinomas of the esophagus.

8) Prior chemotherapy, surgery or radiotherapy for esophageal or gastroesophageal junction cancer. Phase I patients with prior chemotherapy are permitted to enter.

9) Prior radiotherapy that would overlap the anticipated study treatment fields or radiotherapy to =/>30% of the marrow cavity (no prior chest irradiation).

10) Patients with symptomatic hypercalcemia or hypercalcemia that is >Grade 2.

11) Patients with malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel are excluded. Subjects with ulcerative colitis, inflammatory bowel disease, or partial or complete small bowel obstruction are also excluded.

12) Pregnant or nursing females. Fertile patients (male and female) must use effective contraception during and for one month after completion of study treatment as follows: A) Complete abstinence from intercourse from 2 weeks prior to administration of the first dose of therapy until 30 days after the final dose of therapy; or

13) (Continuation of #12) B) Consistent and correct use of one of the following acceptable methods of birth control: a) Male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject; or b) Implants of levonorgestrel; c) Injectable progestogen; d) Any intrauterine device (IUD) with a documented failure rate of less than 1% per year; or e) Oral or patch contraceptives (either combined or Progestogen only), f) Barrier methods including diaphragm or condom with a spermicide.

14) Active secondary malignancy or history of other malignancy within the last 5 years (patients who have been disease-free for 5 years, or have a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma of the cervix are eligible). An 'active' malignancy is one for which treatment is ongoing or there is clinical or radiological evidence of tumor. Patients with a recent history of prostate cancer (i.e., less than 5 years) are permitted to enroll into the Phase I portion of the study.

15) Uncontrolled concurrent illness including, but not limited to: serious uncontrolled infection, symptomatic congestive heart failure (CHF), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with the study requirements.

16) Concurrent treatment with an investigational agent or device within 28 days prior to the first dose of therapy or participation in another clinical investigation.

17) Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, hormonal therapy, targeted therapy, biologic therapy, or tumor embolization) except for study treatment including: docetaxel, 5-FU, and radiation therapy.

18) Known hypersensitivity to gossypol, its enantiomers, or its excipients.

19) Known hypersensitivity to docetaxel, 5-FU or their excipients.

20) Any other condition or circumstance that would, in the opinion of the Investigator, make the patient unsuitable for participation in the study.

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Links
Registration Number: NCT00561197
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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