Clinical trial NCT00049699: VNP40101M in Treating Patients With Advanced or Metastatic Cancer
Official title: A Phase I Trial of VNP40101M, a Novel Alkylating Agent, Administered Weekly for Patients With Advanced or Metastatic Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lymphoma
Small Intestine Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Keywords: anaplastic large cell lymphoma
angioimmunoblastic T-cell lymphoma
intraocular lymphoma
primary central nervous system non-Hodgkin lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult Burkitt 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 mycosis fungoides/Sezary syndrome
small intestine 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 Burkitt 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 mycosis fungoides/Sezary syndrome
unspecified adult solid tumor, protocol specific
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
stage IV small lymphocytic lymphoma
stage IV marginal zone lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
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 cancer cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of VNP40101M in treating patients who have advanced or metastatic cancer.

Detailed description: OBJECTIVES:

* Determine the toxic effects of VNP40101M in patients with advanced or metastatic solid tumor or lymphoma.
* Determine the maximum tolerated dose of this drug in these patients.
* Determine the pharmacokinetics of this drug in these patients.
* Determine the antitumor effects of this drug in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive VNP40101M IV over 15 minutes on days 1, 8, and 15. Treatment repeats every 28 days.

Cohorts of 3-6 patients receive escalating doses of VNP40101M until the maximum tolerated dose is determined.

PROJECTED ACCRUAL: Approximately 20 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed advanced or metastatic solid tumor or lymphoma for which no curative or standard effective therapy exists
* Measurable or evaluable disease
* Primary brain tumors or brain metastases allowed provided neurologic deficits are stable and do not preclude study compliance

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* ECOG 0-1

Life expectancy

* At least 3 months

Hematopoietic

* Granulocyte count at least 1,500/mm\^3
* Platelet count at least 100,000/mm\^3
* Hematocrit at least 30% (transfusion allowed)
* No bleeding diathesis

Hepatic

* PT and PTT no greater than 1.5 times the upper limit of normal (ULN)
* Bilirubin no greater than 1.5 times ULN
* ALT and AST no greater than 1.5 times ULN (3 times ULN if liver metastases present)
* Albumin at least 2.5 gm/dL

Renal

* Creatinine no greater than 2.0 mg/dL

Cardiovascular

* At least 3 months since prior myocardial infarction
* No symptomatic coronary artery disease
* No arrhythmias requiring medication
* No uncontrolled congestive heart failure

Pulmonary

* No dyspnea on minimal or moderate exertion
* DLCO and FEV1 at least 60% predicted

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No uncontrolled active bleeding (e.g., active peptic ulcer disease)
* No active infection
* HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Recovered from acute toxicities of prior biologic therapy (persisting, chronic toxicity allowed if stable and no greater than grade 1)

Chemotherapy

* More than 6 months since prior high-dose chemotherapy with stem cell support
* More than 3 weeks since prior cytotoxic chemotherapy (6 weeks for mitomycin or nitrosoureas)
* Recovered from acute toxicities of prior chemotherapy (persisting, chronic toxicity allowed if stable and no greater than grade 1)

Endocrine therapy

* At least 2 weeks since prior hormonal therapy

Radiotherapy

* Recovered from acute toxicities of prior radiotherapy (persisting, chronic toxicity allowed if stable and no greater than grade 1)

Surgery

* At least 2 weeks since prior surgery

Other

* No other concurrent standard or investigational treatment for cancer
* No concurrent disulfiram

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale Comprehensive Cancer Center
state: Connecticut
city: West Haven
country: United States
facility: Veterans Affairs Medical Center - West Haven
state: Connecticut
city: Cleveland
country: United States
facility: Ireland Cancer Center
state: Ohio
Study officials:
affiliation: Vion Pharmaceuticals
name: Mario Sznol, MD
role: STUDY_CHAIR
References: