A Dose Escalation Study of SF1126, a PI3 Kinase (PI3K) Inhibitor, Given By Intravenous (IV) Infusion in Patients With Solid Tumors

NCT00907205 | Completed Phase 1

• 1 other identifier: SF1126-001-06
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of SF1126 in patients with advanced or metastatic tumors by assessing the dose limiting toxicities (DLTs) and defining the maximum tolerated dose given twice per week for 4 weeks and ultimately define a recommended phase II dose.

Conditions

Advanced or Metastatic Solid Tumors; Cancer; Solid Cancers

Keywords

Advanced Solid Tumors; Metastatic Solid Tumors; PI3K; PI3K Inhibitors; PI3 Kinase Inhibitors; mTORC inhibitor; mTORC1 inhibitor; mTORC2 inhibitor; vascular targeted; conjugate

Outcome Measures

Primary Outcomes (1)

• To assess the dose limiting toxicities (DLTs) of SF1126 and the maximum tolerated dose given twice per week for 4 weeks and ultimately define a recommended phase II dose.

  Assessed at each visit and end of cycle 1

Secondary Outcomes (2)

• To assess any preliminary evidence of anti-tumor activity observed with SF1126

  Through study completion or early study discontinuation

• To characterize the pharmacokinetics following the IV doses on Days 1 and 28

  Cycle 1 Days 1 and 28

Study Arms (1)

SF1126

EXPERIMENTAL

Twice weekly IV infusion

Drug: SF1126

Interventions

SF1126 DRUG

Dose Escalating with 3+ patients in each cohort

SF1126

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To qualify for enrollment, all of the following criteria must be met:
• Written informed consent.
• At least 18 years old.
• Accrual will be limited to patients with tumor types that in the opinion of the investigator is known to have PTEN loss or PI3 Kinase mutations potentially important in the biology of their cancer.
• Only patients with histologically confirmation of advanced solid malignant tumor which is refractory to standard therapies or which no standard therapy exists.
• Eastern Cooperative Oncology Group Performance Status of 0 or 1.
• Life expectancy of \> or = 12 weeks.
• Female subjects are eligible to enter and participate in the study if: they are non-childbearing potential, had a hysterectomy, had a bilateral oophorectomy (ovariectomy), had a bilateral tubal ligation, post-menopausal or childbearing potential with a negative serum pregnancy test at screening and agrees to protection by IUD, vasectomized partner, complete abstinence, double barrier contraception.
• male patients with childbearing potential must agree to use adequate contraception while on study.
• patients on active therapy with well-controlled diabetes as defined by fasting glucose \< 160mg/dL.

You may not qualify if:

• Brain metastases or spinal cord compression, unless treatment was completed at least 4 weeks before entry, and stable without steroid treatment for at least 4 weeks.
• Inadequate bone marrow reserve as demonstrated by an absolute neutrophil count \<1.5 x 10\^9/L or platelet count \< 100 x 10\^9/L (can not be post-transfusion) or hemoglobin \<9 g/dL (can be post-transfusion).
• Serum bilirubin \> or = 1.2 times the upper limit of normal.
• An ALT or AST level \> or = 2.5 times the upper limit of normal. If documented liver metastases are present, the ALT or AST levels must still be less than 2.5 times the upper limit of normal.
• Serum creatinine \> 1.5 times the upper limit of normal or a creatinine clearance of \< or = 50mL/min calculated by the Cockcroft-Gault equation.
• Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory, cardiac \[including life threatening arrhythmias\], hepatic, or renal disease.
• Unresolved toxicity ≥CTC Grade 2 from previous anti-cancer therapy except alopecia (if applicable) unless agreed that the patient can be entered after discussion with the Medical Monitor.
• QTc prolongation defined as a QTc \>450 ms for males or \>470ms for females (Fridericia) for 3 consecutive ECGs; OR prior history of cardiovascular disease including heart failure that meets New York Hearth Association (NYHA) class III and IV definitions, OR history of myocardial infarction/active ischemic heart disease within one year of study entry; OR uncontrolled dysrhythmias; OR poorly controlled angina.
• Participation in a trial of an investigational agent within the prior 30 days.
• Pregnant or breast-feeding females.
• High volume peritoneal or pleural effusions requiring a tap more frequently than every 14 days.
• History of other malignancies except curatively excised carcinoma in situ of the cervix, non-melanomatous skin carcinoma or superficial bladder cancer or other solid tumors curatively treated with no evidence of disease for \> or = 5 years. Other cases will be reviewed and possibly allowed if discussed with and approved by Medical Monitor.
• Patients receiving therapeutic doses of Warfarin.
• Any concurrent condition which in the investigator's opinion makes it undesirable for the subject to participate in this trial or which would jeopardize compliance with the protocol.

Sponsors & Collaborators

• Semafore Pharmaceuticals: lead
• SignalRX Pharmaceuticals, Inc.: collaborator

Study Sites (4)

Scottsdale Clinical Research Institute

Scottsdale, Arizona, 85258, United States

Location

Arizona Cancer Center

Tucson, Arizona, 85719, United States

Location

Emory Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Related Publications (1)

• Mahadevan D, Chiorean EG, Harris WB, Von Hoff DD, Stejskal-Barnett A, Qi W, Anthony SP, Younger AE, Rensvold DM, Cordova F, Shelton CF, Becker MD, Garlich JR, Durden DL, Ramanathan RK. Phase I pharmacokinetic and pharmacodynamic study of the pan-PI3K/mTORC vascular targeted pro-drug SF1126 in patients with advanced solid tumours and B-cell malignancies. Eur J Cancer. 2012 Dec;48(18):3319-27. doi: 10.1016/j.ejca.2012.06.027. Epub 2012 Aug 23.

  PMID: 22921184 RESULT

Related Links

• SignalRx Pharmaceuticals Website

MeSH Terms

Conditions

Neoplasms

Interventions

SF 1126

Study Officials

• Donald L Durden, MD, PhD

  SignalRX Pharmaceuticals, Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2009
• First Posted: May 22, 2009
• Study Start: April 1, 2007
• Primary Completion: January 1, 2011
• Study Completion: April 1, 2011
• Last Updated: June 13, 2013

Record last verified: 2013-06

Locations

US (4)