Clinical trial NCT00003103: Chemotherapy in Treating Patients With Solid Tumors
Official title: A Phase I/IIA Dose-Escalating Trial of BCL-2 Antisense (G3139) Treatment for Patients With Androgen-Independent Prostate Cancer or Other Advanced Solid Tumor Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Bladder Cancer
Breast Cancer
Colorectal Cancer
Esophageal Cancer
Head and Neck Cancer
Kidney Cancer
Lung Cancer
Ovarian Cancer
Prostate Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Keywords: stage III colon cancer
stage IV colon cancer
stage IV breast cancer
stage IIIA breast cancer
recurrent breast cancer
stage IIIB breast cancer
recurrent non-small cell lung cancer
stage III rectal cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer
stage II esophageal cancer
stage III esophageal cancer
stage IV esophageal cancer
recurrent esophageal cancer
stage III renal cell cancer
stage IV renal cell cancer
recurrent renal cell cancer
stage III ovarian epithelial cancer
stage IV ovarian epithelial cancer
recurrent ovarian epithelial cancer
stage III Wilms tumor
stage IV Wilms tumor
stage V Wilms tumor
recurrent Wilms tumor and other childhood kidney tumors
stage III bladder cancer
recurrent bladder cancer
stage IV bladder cancer
stage III prostate cancer
stage IV prostate cancer
recurrent prostate cancer
stage IIIA non-small cell lung cancer
stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer
unspecified adult solid tumor, protocol specific
untreated metastatic squamous neck cancer with occult primary
recurrent metastatic squamous neck cancer with occult primary
ovarian stromal cancer
stage III ovarian germ cell tumor
stage IV ovarian germ cell tumor
recurrent ovarian germ cell tumor
stage III squamous cell carcinoma of the lip and oral cavity
stage III basal cell carcinoma of the lip
stage III verrucous carcinoma of the oral cavity
stage III mucoepidermoid carcinoma of the oral cavity
stage III adenoid cystic carcinoma of the oral cavity
stage IV squamous cell carcinoma of the lip and oral cavity
stage IV basal cell carcinoma of the lip
stage IV verrucous carcinoma of the oral cavity
stage IV mucoepidermoid carcinoma of the oral cavity
stage IV adenoid cystic carcinoma of the oral cavity
recurrent squamous cell carcinoma of the lip and oral cavity
recurrent basal cell carcinoma of the lip
recurrent verrucous carcinoma of the oral cavity
recurrent mucoepidermoid carcinoma of the oral cavity
recurrent adenoid cystic carcinoma of the oral cavity
stage III squamous cell carcinoma of the oropharynx
stage III lymphoepithelioma of the oropharynx
stage IV squamous cell carcinoma of the oropharynx
stage IV lymphoepithelioma of the oropharynx
recurrent squamous cell carcinoma of the oropharynx
recurrent lymphoepithelioma of the oropharynx
stage III squamous cell carcinoma of the nasopharynx
stage III lymphoepithelioma of the nasopharynx
stage IV squamous cell carcinoma of the nasopharynx
stage IV lymphoepithelioma of the nasopharynx
recurrent squamous cell carcinoma of the nasopharynx
recurrent lymphoepithelioma of the nasopharynx
stage III squamous cell carcinoma of the hypopharynx
stage IV squamous cell carcinoma of the hypopharynx
recurrent squamous cell carcinoma of the hypopharynx
stage III squamous cell carcinoma of the larynx
stage III verrucous carcinoma of the larynx
stage IV squamous cell carcinoma of the larynx
stage IV verrucous carcinoma of the larynx
recurrent squamous cell carcinoma of the larynx
recurrent verrucous carcinoma of the larynx
stage III squamous cell carcinoma of the paranasal sinus and nasal cavity
stage III inverted papilloma of the paranasal sinus and nasal cavity
stage III midline lethal granuloma of the paranasal sinus and nasal cavity
stage III esthesioneuroblastoma of the paranasal sinus and nasal cavity
stage IV squamous cell carcinoma of the paranasal sinus and nasal cavity
stage IV inverted papilloma of the paranasal sinus and nasal cavity
stage IV midline lethal granuloma of the paranasal sinus and nasal cavity
stage IV esthesioneuroblastoma of the paranasal sinus and nasal cavity
recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity
recurrent inverted papilloma of the paranasal sinus and nasal cavity
recurrent midline lethal granuloma of the paranasal sinus and nasal cavity
recurrent esthesioneuroblastoma of the paranasal sinus and nasal cavity
borderline ovarian surface epithelial-stromal tumor
ovarian sarcoma
clear cell sarcoma of the kidney
rhabdoid tumor of the kidney
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
First posted: 2004-04-06
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase I/II trial to study the effectiveness of oblimersen in treating patients who have solid tumors that have not responded to previous therapy.

Detailed description: OBJECTIVES: I. Evaluate the safety and plasma concentration profiles of oblimersen (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.

OUTLINE: This is a dose-escalation study of oblimersen (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 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 57 patients (42 for phase I and 15 for phase II) will be accrued for this study.

Eligibility 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

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 3,500/mm3 Platelet count greater than 100,000/mm3 Hepatic: Bilirubin less than 2.0 mg/dL SGOT less than 3 times the upper limit of normal Prothrombin time less than 14 seconds 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

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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Michael Morris, MD
role: STUDY_CHAIR
References: