Advanced Solid Tumors, Lymphoma
Conditions
Keywords
Solid Tumors, Lymphoma, G-Quadruplex
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.
Interventions
DRUGCX-3543
Escalating doses of CX-3543 administered intravenously daily for 5 consecutive days every 21 days.
Sponsors
Cylene Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum tolerated dose (MTD) and Dose limiting toxicity (DLT) | Cycle 1 |
| Recommended Phase 2 dose | Cycle 1 |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Pharmacodynamic evaluation of antitumor activity | Monthly |
Countries
United States
Outcome results
None listed