Dose-escalation Study of Quarfloxin in Patients With Advanced Solid Tumors or Lymphomas
Primary Purpose
Advanced Solid Tumors, Lymphoma
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Quarfloxin
Sponsored by
About this trial
This is an interventional treatment trial for Advanced Solid Tumors focused on measuring Solid Tumors, Lymphoma, G-Quadruplex
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.
- Normal oxygen saturation by pulse oximetry on room air
- A negative pregnancy test (if female).
- Acceptable liver function as evaluated by laboratory results
- Acceptable renal 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 requiring 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 an uncorrectable pulmonary compromise.
- 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 one month 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 agent.
- Patients who have exhibited allergic reactions to a similar structural compound (e.g., fluoroquinolones, biological agent or formulation.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Quarfloxin
Arm Description
Outcomes
Primary Outcome Measures
Maximum tolerated dose (MTD) and Dose limiting toxicity (DLT)
Recommended Phase 2 dose
Secondary Outcome Measures
Pharmacokinetics (PK) in humans of intravenously administered quarfloxin
Evaluation of antitumor activity of quarfloxin by objective radiologic assessment
Pharmacodynamic evaluation of antitumor activity
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00955292
Brief Title
Dose-escalation Study of Quarfloxin in Patients With Advanced Solid Tumors or Lymphomas
Official Title
A Phase I, Multicenter, Open-label, Dose-Escalation, Safety, Pharmacokinetic and Pharmacodynamic Study of Quarfloxin Administered Intravenously Weekly for Three Weeks of a Four Week Cycle in Patients With Advanced Solid Tumors or Lymphomas
Study Type
Interventional
2. Study Status
Record Verification Date
August 2009
Overall Recruitment Status
Terminated
Why Stopped
Modified dose schedule presented no advantage over previously studied schedule
Study Start Date
July 2007 (undefined)
Primary Completion Date
April 2008 (Actual)
Study Completion Date
December 2008 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Cylene Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This phase 1 study of quarfloxin (CX-3543) is designed to test the safety, tolerability, and highest safe dose of this drug when administered intravenously weekly for three weeks of a four week cycle in patients with advanced solid tumors.
Detailed Description
Quarfloxin is a first-in-class small-molecule targeted cancer therapeutic derived from the validated fluoroquinolone class of drugs. Quarfloxin 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Solid Tumors, Lymphoma
Keywords
Solid Tumors, Lymphoma, G-Quadruplex
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Quarfloxin
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Quarfloxin
Other Intervention Name(s)
CX-3543, Quarfloxacin
Intervention Description
Escalating doses of quarfloxin administered intravenously for 24 hours once weekly for three weeks every four weeks
Primary Outcome Measure Information:
Title
Maximum tolerated dose (MTD) and Dose limiting toxicity (DLT)
Time Frame
Cycle 1
Title
Recommended Phase 2 dose
Time Frame
Cycle 1
Secondary Outcome Measure Information:
Title
Pharmacokinetics (PK) in humans of intravenously administered quarfloxin
Time Frame
One month
Title
Evaluation of antitumor activity of quarfloxin by objective radiologic assessment
Time Frame
Every 2 months
Title
Pharmacodynamic evaluation of antitumor activity
Time Frame
Monthly
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Normal oxygen saturation by pulse oximetry on room air
A negative pregnancy test (if female).
Acceptable liver function as evaluated by laboratory results
Acceptable renal 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 requiring 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 an uncorrectable pulmonary compromise.
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 one month 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 agent.
Patients who have exhibited allergic reactions to a similar structural compound (e.g., fluoroquinolones, biological agent or formulation.
Facility Information:
City
Scottsdale
State/Province
Arizona
Country
United States
City
San Antonio
State/Province
Texas
Country
United States
12. IPD Sharing Statement
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Dose-escalation Study of Quarfloxin in Patients With Advanced Solid Tumors or Lymphomas
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