Dose-escalation Study of CX-3543 in Patients With Advanced Solid Tumors or Lymphomas

A Phase I, Multicenter, Open-label, Dose-Escalation, Safety and Tolerance, and Pharmacokinetic Study of Intravenously Administered CX-3543,on a Daily x 5, Repeated Every 3 Weeks Schedule, in Patients With Advanced Solid Tumors or Lymphomas

This phase 1 study of CX-3543 is designed to test the safety, tolerability and highest safe dose level of this drug in patients with advanced solid tumor cancers.

Study Overview

• Status: Completed
• Conditions: Lymphoma; Advanced Solid Tumors
• Intervention / Treatment: Drug: CX-3543

Detailed Description

CX-4945 is a first-in-class small-molecule targeted cancer therapeutic derived from the validated fluoroquinolone class of drugs. This drug was rationally designed to target a G-quadruplex (QPLX) DNA structure and disrupt protein-DNA interactions essential to cancer cells. The QPLX targeted by quarfloxin forms within ribosomal DNA (rDNA) and the QPLX is bound by the nucleolin protein.This Phase 1 study of CX-3543 is designed to test the safety, tolerability and highest safe dose level of this drug in patients with advanced solid tumor cancers.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
  • Texas
    • San Antonio, Texas, United States, 78229

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:

• Patients with histologically confirmed solid tumors or lymphomas.
• Tumor progression after receiving standard/approved chemotherapy or where there is no approved therapy.
• One or more tumors measurable on radiograph or CT scan, or evaluable disease. (e.g., malignant ascites)
• Karnofsky performance status of greater than or equal to 70.
• Life expectancy of at least 3 months.
• Age at least 18 years.
• Patients must have central IV access, or agree to the insertion of a central IV line.
• A negative urine pregnancy test (if female.)
• Acceptable liver function as evaluated by laboratory results
• Acceptable hematologic status as evaluated by laboratory results
• No clinically significant urinalysis abnormalities
• Acceptable coagulation status as evaluated by laboratory results
• Fertile men and women must use effective contraceptive methods during the study.

Exclusion Criteria:

• Seizure disorders not controlled by anticonvulsant therapy.
• Known brain metastases (unless previously treated and well controlled for a period of greater than or equal to 3 months.)
• Severe chronic obstructive pulmonary disease with hypoxemia or a pulmonary compromise not correctable with therapy.
• Major surgery, other than diagnostic surgery, within 4 weeks prior to the first dose of test drug.
• Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy.
• Pregnant or nursing women.
• Treatment with radiation therapy, surgery, chemotherapy, or investigational therapy within 4 weeks prior to study entry (6 weeks for nitrosoureas or Mitomycin C.)
• Unwillingness or inability to comply with procedures required in this protocol.
• Known infection with HIV, hepatitis B, or hepatitis C.
• Clinically significant bleeding event within the last 3 months, unrelated to trauma, or underlying condition that would be expected to result in a bleeding diathesis.
• Patients who are currently receiving any other investigational therapy.
• Patients who have exhibited allergic reactions to a similar structural compound (e.g., fluoroquinolones), biological agent, or formulation.

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: CX-3543	Drug: CX-3543; Escalating doses of CX-3543 administered intravenously daily for 5 consecutive days every 21 days.; Other Names: quarfloxacin; quarfloxin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum tolerated dose (MTD) and Dose limiting toxicity (DLT)	Cycle 1
Recommended Phase 2 dose	Cycle 1

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacodynamic evaluation of antitumor activity	Monthly
Pharmacokinetics (PK) in humans of intravenously administered CX-3543.	Monthly
Evaluate evidence of antitumor activity of CX-3543 by objective radiographic assessment.	Every two months

Collaborators and Investigators

• Sponsor: Cylene Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: July 1, 2005
• Primary Completion (Actual): July 1, 2007
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: August 6, 2009
• First Submitted That Met QC Criteria: August 7, 2009
• First Posted (Estimate): August 10, 2009

Study Record Updates

• Last Update Posted (Estimate): August 10, 2009
• Last Update Submitted That Met QC Criteria: August 7, 2009
• Last Verified: August 1, 2009

More Information

Terms related to this study

• Keywords: Lymphoma; Solid Tumors; G-Quadruplex
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma
• Other Study ID Numbers: C3-05-001