Clinical trial NCT00025129: VNP40101M in Treating Patients With Advanced Solid Tumors or Lymphomas
Official title: A Phase I Trial of VNP4010M, A Novel Alkylating Agent 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: stage IV adult Hodgkin lymphoma
recurrent adult Hodgkin lymphoma
stage IV cutaneous T-cell non-Hodgkin lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
small intestine lymphoma
unspecified adult solid tumor, protocol specific
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
stage IV adult lymphoblastic lymphoma
stage IV adult Burkitt lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent adult Burkitt lymphoma
stage IV adult T-cell leukemia/lymphoma
recurrent adult T-cell leukemia/lymphoma
primary central nervous system non-Hodgkin lymphoma
intraocular lymphoma
stage IV mantle cell lymphoma
recurrent mantle cell lymphoma
angioimmunoblastic T-cell lymphoma
anaplastic large cell lymphoma
stage IV mycosis fungoides/Sezary syndrome
recurrent mycosis fungoides/Sezary syndrome
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 solid tumors or lymphomas.

Detailed description: OBJECTIVES:

* Determine the maximum tolerated dose of VNP40101M in patients with advanced solid tumors or lymphomas.
* Determine the toxic effects of this drug in these patients.
* Determine the pharmacokinetics of this drug in these patients.
* Determine the anti-tumor effects of this drug in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive VNP40101M IV over 15 minutes on day 1. Treatment repeats every 4 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 1-6 patients receive escalating doses of VNP40101M until the maximum tolerated dose (MTD) is determined. The MTD is defined as the highest dose at which no more than 1 of 6 patients experiences dose-limiting toxicity.

PROJECTED ACCRUAL: Approximately 20-30 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed advanced and/or metastatic solid tumor or lymphoma for which no curative or standard effective therapy exists
* Measurable or evaluable metastatic disease
* No other hematologic malignancy
* No large pleural, pericardial, or peritoneal effusions
* No requirement for immediate palliative treatment, including surgery
* No symptomatic brain metastases or metastases with substantial edema

  * Asymptomatic brain metastases or primary CNS disease allowed if neurologic deficits are stable

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 active uncontrolled bleeding

Hepatic:

* Bilirubin no greater than 1.5 times upper limit of normal (ULN)
* ALT and AST no greater than 1.5 times ULN (3 times ULN if liver metastases present)
* Alkaline phosphatase no greater than 1.5 times ULN (3 times ULN if liver or bone metastases present)
* PT and aPTT no greater than 1.5 times ULN
* Albumin at least 2.5 g/dL

Renal:

* Creatinine no greater than 2.0 mg/dL

Cardiovascular:

* Ejection fraction at least 45%
* No active heart disease
* No myocardial infarction within the past 3 months
* No symptomatic coronary artery disease
* No arrhythmias requiring medication
* No uncontrolled congestive heart failure

Pulmonary:

* DLCO and FEV_1 at least 60% of predicted
* No dyspnea with minimal to moderate exertion

Other:

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for 3 months after study participation
* HIV negative
* No active infection
* Persistent stable chronic toxic effects from prior therapy allowed if no greater than grade 1
* No bleeding diathesis (e.g., active peptic ulcer disease)

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* At least 3 weeks since prior biologic agents and recovered
* At least 6 months since prior high-dose chemotherapy regimen with stem cell support

Chemotherapy:

* See Biologic therapy
* At least 3 weeks since prior cytotoxic agents (6 weeks for nitrosoureas or mitomycin) and recovered

Endocrine therapy:

* At least 2 weeks since prior hormonal therapy and recovered

Radiotherapy:

* At least 3 weeks since prior radiotherapy and recovered

Surgery:

* See Disease Characteristics
* At least 2 weeks since prior surgery and recovered

Other:

* No other concurrent standard therapy for cancer
* No other concurrent investigational agents
* No concurrent disulfiram (Antabuse)

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Clinical Research Center
state: Arizona
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
Study officials:
affiliation: Vion Pharmaceuticals
name: Mario Sznol, MD
role: STUDY_CHAIR
References: