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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Advanced Solid Tumors, Lymphoma

Intervention / Treatment
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* Drug: CX-3543


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CX-3543<br> | Drug: CX-3543<br>* Escalating doses of CX-3543 administered intravenously daily for 5 consecutive days every 21 days.<br>* Other names: quarfloxin;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Solid Tumors, Lymphoma, G-Quadruplex