Clinical trial NCT00955786: Dose-escalation Study of CX-3543 in Patients With Advanced Solid Tumors or Lymphomas
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Lymphoma
Keywords: Solid Tumors
Lymphoma
G-Quadruplex
Lead sponsor: Cylene Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2009-08-10
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Maximum tolerated dose (MTD) and Dose limiting toxicity (DLT)
timeFrame: Cycle 1
measure: Recommended Phase 2 dose
timeFrame: Cycle 1
Secondary outcomes:
measure: Pharmacokinetics (PK) in humans of intravenously administered CX-3543.
timeFrame: Monthly
measure: Evaluate evidence of antitumor activity of CX-3543 by objective radiographic assessment.
timeFrame: Every two months
measure: Pharmacodynamic evaluation of antitumor activity
timeFrame: Monthly
Other outcomes:
Locations:
city: Scottsdale
country: United States
state: Arizona
city: San Antonio
country: United States
state: Texas
Study officials:
References: