RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of augmerosen in treating patients who have solid tumors that have not responded to previous therapy.

Condition	Treatment or Intervention	Phase
Gastrointestinal Cancer Head and Neck Cancer Kidney Cancer Lung Cancer Oral Cancer Reproductive Cancers	Drug: augmerosen  Drug: docetaxel	Phase I Phase II

Further Study Details: 

OBJECTIVES: I. Evaluate the safety and plasma concentration profiles of augmerosen (G3139) administered alone or in combination with docetaxel in patients with advanced solid tumors expressing the bcl-2 oncogene. II. Determine the plasma concentration profiles, maximum tolerated dose (MTD), and/or optimal biologic dose (OBD) of this treatment regimen in these patients. III. Determine the antitumor effects of G3139, at the MTD or OBD, in combination with docetaxel in patients with androgen independent, refractory, or recurrent prostate cancer.

PROTOCOL OUTLINE: This is a dose-escalation study of augmerosen (G3139). Phase I: Patients receive G3139 IV on days 1-5 and docetaxel IV on day 5. Treatment repeats every 21 days for up to 6 courses of therapy in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of G3139 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Phase II: Patients receive G3139 continuously over 21 days at one dose level below the MTD in combination with weekly docetaxel. Patients receive up to 2 more courses of therapy in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months until disease progression.

PROJECTED ACCRUAL: A maximum of 42 patients will be accrued for phase I, and a total of 15 patients will be accrued for phase II, for a maximum accrual of 57 patients.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Phase I: Histologically proven advanced, primary, or malignant solid tumors that are refractory to standard therapy or for which no curative therapy exists; Androgen independent prostate cancer; Head and neck cancers; Breast cancer; Non-small cell lung cancer; Colorectal cancer; Ovarian cancer; Esophageal cancer; Bladder cancer; Kidney cancer; Other solid tumors; Metastatic disease should not require palliative treatment within 4 weeks of enrollment
• Phase II: Histologically proven androgen independent prostate cancer; Serum testosterone less than 30 ng/Ml Failed at least one prior chemotherapy regimen; Progressive; Minimum of 3 rising PSA values from baseline obtained at least 1 week apart OR Two rising PSA values more than one month apart AND At least 25% increase over range of values AND PSA at least 4 ng/Ml
• No active CNS or epidural tumor
• Hormone receptor status: Not specified

--Prior/Concurrent Therapy--

• Biologic therapy: No concurrent immunotherapy
• Chemotherapy: At least 4 weeks since prior chemotherapy and recovered
• Endocrine therapy: Concurrent medical therapy (i.e., gonadotropin releasing hormone analogs or diethylstilbestrol) to maintain castrate levels of serum testosterone allowed; No other concurrent hormonal therapy
• Radiotherapy: At least 4 weeks since prior radiotherapy and recovered; Concurrent radiotherapy to localized sites of disease not being evaluated in study allowed
• Surgery: Not specified
• Other: At least 4 weeks since prior investigational anticancer therapy and recovered; No concurrent intravenous antibiotics

--Patient Characteristics--

• Age: 18 and over
• Sex: Not specified
• Menopausal status: Not specified
• Performance status: Karnofsky 60-100%
• Life expectancy: At least 6 months
• Hematopoietic: WBC greater than 3500/mm3; Platelet count greater than 100,000/mm3; Prothrombin time less than 14 seconds
• Hepatic: Bilirubin less than 2.0 mg/dL; SGOT less than 3 times the upper limit of normal
• Renal: Creatinine less than 2.0 mg/dL OR Creatinine clearance greater than 60 mL/min
• Cardiovascular: No New York Heart Association class III or IV cardiac disease
• Pulmonary: No severe debilitating pulmonary disease
• Other: Not pregnant or nursing; Fertile patients must use effective contraception; No active infection; No other severe medical problems

New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States

Study chairs or principal investigators

Michael Morris,  Study Chair,  Memorial Sloan-Kettering Cancer Center   

Study ID Numbers:  CDR0000065836; MSKCC-97096; NCI-G97-1337; GENTA-G3139-97/01
Record last reviewed:  April 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003103
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08