Study of the Vascular Disrupting Agent NPI-2358 in Patients With Advanced Solid Tumors or Lymphoma

Phase I Study of the Vascular Disrupting Agent NPI-2358 Administered Via Intravenous Infusion in Patients With Advanced Solid Tumor Malignancies or Lymphoma

This is a Phase 1 clinical trial examining the safety, pharmacokinetics and pharmacodynamics of escalating doses of the vascular disrupting agent NPI-2358 in patients with refractory solid tumors or lymphoma. The formation of new blood vessels (angiogenesis) is an important component of tumor growth and vascular disrupting agents are intended to target the differences between these tumor blood vessels and the blood vessels in normal tissues. NPI-2358 has also been seen to directly affect tumor cells.

Study Overview

• Status: Completed
• Conditions: Cancer
• Intervention / Treatment: Drug: NPI-2358

• Study Type: Interventional
• Enrollment (Anticipated): 35
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Barbara Ann Karmanos Cancer Institute/Wayne State University
  • Texas
    • San Antonio, Texas, United States, 78245-3217
      • Institute for Drug Development
  • Washington
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ECOG performance status ≤ 2
• Pathologically or histologically confirmed solid tumor malignancy
• Patients must not be candidates for regimens known to provide clinical benefit.
• All adverse events of any prior chemotherapy, surgery, or radiotherapy, must have resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (v. 3.0) Grade ≤ 2, except for neurological toxicity that must have resolved to Grade ≤ 1.
• Adequate bone marrow reserve, hepatic and renal function
• Signed informed consent

Exclusion Criteria:

• Administration of chemotherapy, biological, immunotherapy or investigational agent (therapeutic or diagnostic) within 21 days prior to receipt of study medication (6 weeks for nitrosoureas or mitomycin C; 12 weeks for radioimmunotherapy). Major surgery, other than diagnostic surgery, within 6 weeks before first study drug administration. Radiotherapy within 4 weeks (some types of radiation therapy are excluded regardless of interval since treatment).
• Significant cardiac history or findings
• Underlying conditions or medications associated with bleeding diathesis
• Disorders associated with significant vascular pathology
• Lung cancer with central chest tumors
• Prior treatment with vascular disruptive agents
• Seizure disorder requiring anticonvulsant therapy; prior transient ischemic attack or cerebrovascular accident
• Brain metastases
• Severe chronic obstructive pulmonary disease (COPD) with hypoxemia
• Active uncontrolled bacterial, viral, or fungal infection, requiring systemic therapy
• Known infection with human immunodeficiency virus (HIV), active hepatitis A, B, or C
• Patients with a prior hypersensitivity reaction to any product containing Solutol and/or propylene glycol
• Pregnant or breast-feeding women. Female patients must be postmenopausal, surgically sterile or they must agree to use acceptable methods of birth control. Female patients with childbearing potential must have a negative serum pregnancy test. Male patients must be surgically sterile or agree to use an acceptable method of contraception.
• Concurrent, active second malignancy for which the patient is receiving therapy, excluding basal cell carcinoma of the skin or carcinoma in situ of the cervix

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose escalation	Drug: NPI-2358; Treatment on Days 1, 8 and 15 in a 28 day cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety	continuously
Tolerability	continuously
Maximum tolerated dose (MTD)	continuously

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics	continuously
Pharmacodynamics	continuously
Response Evaluation Criteria in Solid Tumors (RECIST)	continuously

Collaborators and Investigators

• Sponsor: Nereus Pharmaceuticals, Inc.
• Investigators: Study Director: Matthew A Spear, M.D., Chief Medical Officer, Nereus Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start: April 1, 2006
• Primary Completion (Actual): September 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: May 4, 2006
• First Submitted That Met QC Criteria: May 4, 2006
• First Posted (Estimate): May 8, 2006

Study Record Updates

• Last Update Posted (Estimate): January 10, 2011
• Last Update Submitted That Met QC Criteria: January 6, 2011
• Last Verified: January 1, 2011

More Information

Terms related to this study

• Keywords: Solid Tumors; Lymphomas
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma
• Other Study ID Numbers: NPI-2358-100