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

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00955292
• Other study ID #: C3-07-002
• Status: Terminated
• Phase: Phase 1
• First received: August 7, 2009
• Last updated: August 7, 2009
• Start date: July 2007
• Est. completion date: December 2008

Study information

• Verified date: August 2009
• Source: Cylene Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 12
• Est. completion date: December 2008
• Est. primary completion date: April 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Lymphoma

Intervention

Drug:
• Quarfloxin
Escalating doses of quarfloxin administered intravenously for 24 hours once weekly for three weeks every four weeks

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Cylene Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose (MTD) and Dose limiting toxicity (DLT)		Cycle 1	Yes
Primary	Recommended Phase 2 dose		Cycle 1	Yes
Secondary	Pharmacokinetics (PK) in humans of intravenously administered quarfloxin		One month	No
Secondary	Evaluation of antitumor activity of quarfloxin by objective radiologic assessment		Every 2 months	No
Secondary	Pharmacodynamic evaluation of antitumor activity		Monthly	No