Clinical trial NCT00060112: Oblimersen and Gemcitabine in Treating Patients With Advanced Solid Tumor or Lymphoma
Official title: A Phase I Study of Oblimersen (Genasense™, G3139) in Combination With Gemcitabine in Advanced Malignancies
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Nodal Marginal Zone B-cell Lymphoma
Recurrent Adult Burkitt Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Diffuse Mixed Cell Lymphoma
Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
Recurrent Adult Hodgkin Lymphoma
Recurrent Adult Immunoblastic Large Cell Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Adult T-cell Leukemia/Lymphoma
Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Small Lymphocytic Lymphoma
Splenic Marginal Zone Lymphoma
Stage IV Adult Burkitt Lymphoma
Stage IV Adult Diffuse Large Cell Lymphoma
Stage IV Adult Diffuse Mixed Cell Lymphoma
Stage IV Adult Diffuse Small Cleaved Cell Lymphoma
Stage IV Adult Hodgkin Lymphoma
Stage IV Adult Immunoblastic Large Cell Lymphoma
Stage IV Adult Lymphoblastic Lymphoma
Stage IV Adult T-cell Leukemia/Lymphoma
Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma
Stage IV Grade 1 Follicular Lymphoma
Stage IV Grade 2 Follicular Lymphoma
Stage IV Grade 3 Follicular Lymphoma
Stage IV Mantle Cell Lymphoma
Stage IV Marginal Zone Lymphoma
Stage IV Small Lymphocytic Lymphoma
Unspecified Adult Solid Tumor, Protocol Specific
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-05-07
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Drugs used in chemotherapy such as gemcitabine use different ways to stop cancer cells from dividing so they stop growing or die. Oblimersen may increase the effectiveness of gemcitabine by making cancer cells more sensitive to the drug. This phase I trial is studying the side effects and best dose of oblimersen and gemcitabine in treating patients with metastatic or unresectable solid tumors or lymphoma

Detailed description: PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose and dose-limiting toxicity of oblimersen and gemcitabine in patients with advanced solid tumor or lymphoma.

II. Determine the effect of oblimersen on the pharmacokinetics and pharmacodynamics of gemcitabine in these patients.

III. Determine the toxic effects of this regimen in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive oblimersen IV continuously on days 1-5 and gemcitabine IV over 2-3 hours on day 5. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of oblimersen and gemcitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Up to 10 additional patients receive treatment at the MTD.

PROJECTED ACCRUAL: Approximately 15 patients will be accrued for this study within 6-8 months.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed malignancy for which there is no standard or effective curative or palliative therapy

  * Solid tumors and lymphoma allowed
  * Metastatic or unresectable disease
* Measurable or evaluable nonmeasurable disease

  * Evaluable nonmeasurable disease includes ascites, pleural/pericardial effusions, lymphangitis cutis/pulmonis, inflammatory breast disease, abdominal masses not followed by CT scan or MRI, or cystic lesions
  * Disease characterized by elevated serum tumor marker alone is allowed
* No known brain metastases
* Performance status - ECOG 0-2
* Performance status - Karnofsky 60-100%
* More than 3 months
* Absolute neutrophil count at least 1,500/mm\^3
* Platelet count at least 100,000/mm\^3
* Bilirubin no greater than 1.5 mg/dL
* AST and ALT no greater than 2.5 times upper limit of normal
* No history of portal hypertension
* No history of cirrhosis or hepatitis
* No radiographic evidence of cirrhosis and/or varices
* Creatinine normal
* Creatinine clearance at least 60 mL/min
* No symptomatic congestive heart failure
* No unstable angina pectoris
* No cardiac arrhythmia
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No prior allergic reaction attributed to compounds of similar chemical or biological composition to oblimersen or other study agents
* No other concurrent uncontrolled illness that would preclude study participation
* No ongoing or active infection
* No psychiatric illness or social situation that would preclude study compliance
* No concurrent prophylactic colony-stimulating factors such as filgrastim (G-CSF) or sargramostim (GM-CSF)
* Concurrent interventional growth factors allowed

  * No growth factor administration within 24 hours before study chemotherapy
* Concurrent epoetin alfa allowed
* No more than 3 prior chemotherapy regimens
* More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
* More than 2 weeks since prior hormonal therapy
* Concurrent megestrol for anorexia/cachexia allowed
* No prior pelvic or whole abdominal radiotherapy
* More than 4 weeks since prior radiotherapy
* More than 4 weeks since prior major surgery
* Recovered from prior therapy
* More than 4 weeks since prior investigational therapy
* No prior oblimersen
* No other concurrent investigational agents
* No other concurrent anticancer therapy
* No concurrent combination antiretroviral therapy for HIV-positive patients

Primary outcomes:
measure: MTD defined as the dose level at which less than 2 out of 6 patients experience DLT assessed using NCI CTC version 2.0
timeFrame: 4 weeks
Secondary outcomes:
measure: Pharmacokinetics
timeFrame: Pre-dose, 4, 8, 12, 24, 48, 72, 96, 120, 121.67, 126, and 129 hours
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University
state: California
Study officials:
affiliation: Stanford University
name: Branimir (Brandy) Sikic
role: PRINCIPAL_INVESTIGATOR
References: