Effect on QTc, Pharmacokinetics, Safety, and Preliminary Efficacy of Single-agent Palifosfamide-tris in Subjects With Advanced Solid Tumors

Phase 1

• Conditions: Advanced Solid Tumors
• Interventions: Drug: palifosfamide-tris; Drug: Normal Saline

• Registration Number: NCT01340547
• Lead Sponsor: Alaunos Therapeutics

Brief Summary

This is an open-label study of palifosfamide-tris administered intravenously on Days 1, 2, and 3 of a 21-day cycle to subjects with advanced solid tumors. Enrolled subjects will receive a placebo-control infusion on Day -1 and then commence palifosfamide-tris study treatment 24 hours later on Day 1.

Time-matched, intensive ECG monitoring will occur during and following placebo and palifosfamide-tris infusions on Days -1, 1, 2, 3 and 8. Generation of ECG data for study analysis will be performed in a blinded fashion at a central ECG laboratory.

Blood and urine sampling to characterize the pharmacokinetics of palifosfamide-tris will be performed on Days 1 through 8 of Cycle 1.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-04-13
• Study First Submitted QC: 2011-04-19
• Study First Posted: 2011-04-22
• Study Start: 2011-06
• Status Verified: 2013-07
• Last Update Submitted: 2013-07-17
• Last Update Posted: 2013-07-18
• Primary Completion: 2013-09
• Study Completion: 2013-09

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

Not provided

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Exclusion Criteria

1. Subjects who have received prior chemotherapy, radiation therapy or any investigational agent within 28 days prior to the first dose of study drug.
2. Unstable or clinically significant concurrent medical condition that would, in the opinion of the investigator, jeopardize the safety of a subject and/or their compliance with the protocol. Examples include, but are not limited to, unstable angina, congestive heart failure, recent (within 2 months of screening) myocardial infarction, ongoing maintenance therapy for life-threatening ventricular arrhythmia, uncontrolled asthma, HIV/AIDS without adequate anti-viral therapy, evidence of hepatic pathology due to or consistent with infection with a chronic hepatitis virus, uncontrolled major seizure disorder, or electrolyte imbalances.
3. Presence of, or history of any illness or injury to the urinary tract (renal or post-renal) which may make the subject more susceptible to acute renal insufficiency in the case of potential renal adverse events. Types of injury or illness might include a history of polycystic renal disease, nephrectomy, renal transplant, acute or chronic renal failure.
4. Active infection requiring systemic antibacterial, antifungal, or antiviral therapy within 2 weeks of the first dose of study drug. Subjects with HIV who are on effective anti-viral therapy or subjects with chronic herpes infections who use intermittent suppressive antiviral therapy for viral outbreaks may be included.
5. Major surgery within 4 weeks prior to start of treatment.
6. Documented symptomatic brain metastases. Screening for brain lesions by CT or MRI is not required for potential subjects; however, if there are any neurological signs or symptoms consistent with brain metastases, then a brain CT or MRI should be performed as clinically indicated.
7. Currently pregnant or nursing.
8. Subjects with implantable pacemaker or automatic implantable cardioverter defibrillator.
9. Conditions that make the screening ECG repolarization difficult to interpret, or showing significant abnormalities. This includes, but is not limited to: high degree AV block, pace-maker, atrial fibrillation or flutter, prolonged QTc >500ms on repeat measurements (e.g., 2 out of 3 ECGs), or bradycardia (defined as ≤ 50 beats/minute).
10. Subjects who will be receiving medications that prolong the QT interval with a risk of causing Torsades de Pointes during the time period beginning 1 week prior to and during the Intensive ECG monitoring period (i.e., Cycle 1, Day -8 through Day 8).

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Single Arm	palifosfamide-tris	Single Arm, non-blinded, non-randomized
Single Arm	Normal Saline	Single Arm, non-blinded, non-randomized

Primary Outcome Measures

Name	Time	Method
ECG QTc intervals of patients who receive palifosfamide-tris	Cycle 1 Days -1,1, 2, 3,8	To assess the effect of single-agent palifosfamide-tris on QTc intervals.
Blood sampling to characterize the pharmacokinetics of palifosfamide-tris	Cycle 1, Day 1, 2, 3, 4, 8	To assess the pharmacokinetic profile of single-agent palifosfamide-tris.

Secondary Outcome Measures

Name	Time	Method
Safety and tolerability of palifosfamide-tris measured in amount, type, severity and relatedness of Adverse Events	Duration of time patient is on study, expected average of 5 months	To assess the safety and tolerability of single-agent palifosfamide-tris.
Preliminary efficacy of palifosfamide-tris as it pertains to cancer tumor growth	Duration of time patient is on study, expected average of 5 months	To obtain preliminary efficacy data as defined by objective response rate (ORR); progression-free survival (PFS); and durability of response in subjects with advanced solid tumors when treated with single-agent palifosfamide-tris.