Phase 1 Safety Study of ACT-PFK-158, 2HCl in Patients With Advanced Solid Malignancies

• ClinicalTrials.gov Identifier: NCT02044861
• Recruitment Status: Unknown
• First Posted: January 24, 2014
• Last Update Posted: June 23, 2015
• Sponsor: Advanced Cancer Therapeutics
• Information provided by (Responsible Party): Advanced Cancer Therapeutics

Tracking Information

• First Submitted Date: January 22, 2014
• First Posted Date: January 24, 2014
• Last Update Posted Date: June 23, 2015
• Study Start Date: March 2014
• Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: January 23, 2014): Maximum Tolerated Dose [ Time Frame: End of cycle 1 (an average of 1 month) ]
• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT02044861 on ClinicalTrials.gov Archive Site
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase 1 Safety Study of ACT-PFK-158, 2HCl in Patients With Advanced Solid Malignancies
• Official Title: Phase 1 Open-Label, Dose Escalation, Multi-Center Study of ACT-PFK-158, 2HCl in Patients With Advanced Solid Malignancies
• Brief Summary: ACT-PFK-158 is a novel anti-cancer agent that inhibits glucose uptake in cancer cells. The primary objective of the study will be to determine the maximum tolerated dose (MTD) and to describe any dose limiting toxicity. The secondary objectives of the study will be to determine the safety profile of the drug, to determine the pharmacokinetic profile, to identify any anti-tumor activity, and to determine the pharmacodynamic profile of ACT-PFK-158.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Cancer

Intervention

Drug: PFK-158

IV dose escalation

Study Arms

Experimental: ACT-PFK-158

dose escalation

Intervention: Drug: PFK-158

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: June 22, 2015): 56
• Original Enrollment: Not Provided
• Study Completion Date: Not Provided
• Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Histological or cytological evidence of solid malignancy.

2. Patients must have:

   • a. Have advanced solid tumors that are refractory to established therapies known to provide clinical benefit for the malignancy in question, OR
   • b. Be intolerant of established therapies known to provide clinical benefit for the malignancy in question
3. Patients enrolled in the dose-expansion part of the trial must have at least one lesion that may qualify as a target lesion based on the RECIST 1.1 criteria.
4. Patient is ambulatory with an ECOG performance status of 0, 1 or 2 and an estimated life expectancy of > 3 months.
5. Patient is 18 years and older.
6. Patients or their legal representatives must have the ability to read, understand and provide written informed consent for the initiation of any study related procedures.

7. Patients must have adequate bone marrow reserve as evidenced by:

   • a. WBC > 3,000/µL
   • b. Absolute neutrophil count (ANC) ≥ 1,500/µL
   • c. Platelet count ≥ 100,000/µL
   • d. Hemoglobin ≥ 9 gm/dL.
8. Patients must have adequate renal function as evidenced by a serum creatinine ≤ 1.5 X ULN for the reference laboratory OR a calculated creatinine clearance of ≥ 60 mL/min by the Cockroft-Gault equation.
9. Patients must have adequate hepatic function as evidenced by AST and ALT values ≤ 3 X ULN (≤ 5 X ULN if the liver is known to be involved by metastatic disease) and serum total bilirubin values of ≤ 1.5 X ULN for the reference laboratory.
10. Patients must have INR and PTT values ≤ 1.5X ULN for the reference laboratory.
11. Patients must be recovered from the effects of any prior chemotherapy, radiotherapy or surgery (i.e., toxicity no worse than Grade 1); for patients who have been on monoclonal antibody therapy, at least one half-life or 4 weeks (whichever is shorter) should have elapsed prior to the first scheduled day of dosing with PFK-158.
12. Patients on prior investigational agents must wait at least 5 half-lives before enrollment into the trial, or 4 weeks if the half-life of the investigational agent is not known.
13. Female patients of childbearing potential must have a negative pregnancy test within 7 days of the start of treatment.
14. Women of childbearing potential and men with female sexual partners of childbearing potential must agree to use an effective method of contraception (e.g., oral contraceptives, double-barrier methods such as a condom and a diaphragm, intrauterine device) during the study and for 90 days following the last dose of study medication or to abstain from sexual intercourse for this time; a woman not of childbearing potential is one who has undergone bilateral oophorectomies or who is post-menopausal, defined as no menstrual periods for 12 consecutive months.

Exclusion Criteria:

1. Patients with an active infection or with a fever ≥ 38.5°C within 3 days of the first scheduled day of dosing.
2. Patients with primary CNS tumors as well as patients with CNS metastases are excluded.
3. Patients with known hypersensitivity to any of the components of PFK-158.
4. Patients who are receiving investigational therapies or who have been treated with investigational therapies or investigational devices within 5 half-lives of the investigational therapy or 4 weeks of first scheduled day of dosing with PFK-158 if the half-live of the investigational agent is not known.
5. Uncontrolled hypertension as defined by SBP > 160 mm/Hg or DBP > 100 mm/Hg despite medical therapy.
6. Subjects with diabetes.
7. Patients who require pharmacologic doses of corticosteroids; replacement, topical, ophthalmologic and inhalational steroids are permitted.
8. Patients who require coumadin administration.
9. Patients with mean QTcF values of > 470 msec (in females) or > 450 msec (in males) following 3 ECGs conducted 5 minutes apart from each other; patients who are known to have congenital prolonged QT syndromes; or patients who are on medications known to cause prolonged QT intervals on ECG.
10. Patients with clinically significant cardiovascular co-morbidities including: congestive heart failure (New York Heart Association class III-IV heart disease), unstable angina pectoris, cardiac arrhythmias requiring medication or a pacemaker; myocardial infarction within the past six months; stroke within the past 6 months; or hypertension requiring more than 2 medications for blood pressure control.
11. Patients with any other concurrent uncontrolled illness, including mental illness or substance abuse, which may interfere with the ability of the patient to cooperate and participate in the trial; other examples of such conditions would include COPD or diabetes mellitus that has required 2 or more hospitalizations in the last year; severe peripheral vascular disease; poorly controlled auto-immune conditions; recent serious trauma.
12. Grade 2 or higher peripheral neuropathy.
13. Patients currently known to be positive for, HIV, hepatitis B or C.
14. Patients who are pregnant or lactating.
15. Concurrent or recent (within 1 month) use of thrombolytic agents, or full-dose anticoagulants (except to maintain patency of preexisting, permanent indwelling IV catheters). Of note, therapy with low-molecular weight heparin is acceptable as long as the INR < 2.0.
16. Significant traumatic injury within the past 4 weeks.
17. Patients who are in-patients.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02044861
• Other Study ID Numbers: ACT-PFK-01
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Advanced Cancer Therapeutics
• Study Sponsor: Advanced Cancer Therapeutics
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Advanced Cancer Therapeutics
• Verification Date: June 2015