Phase 1 Trial of Intravenously Administered Nerofe™ in Subjects With Advanced Malignancies

NCT01690741 | Completed Phase 1 DMC

• 1 other identifier: ISK-N101
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

This study will be the first to test the anti-cancer peptide Nerofe in humans. It will evaluate the safety, pharmacokinetic behavior, and pharmacodynamic and clinical effects of Nerofe given intravenously every other day to patients with advanced malignant disease.

Conditions

Cancer

Keywords

Cancer; Malignancy; Solid tumors

Outcome Measures

Primary Outcomes (1)

• Safety, as determined by frequency, nature, and severity of adverse events; and the profile of dose-limiting toxicities

  Up to 6 months

Secondary Outcomes (5)

• Pharmacodynamic effects of Nerofe, through the measurement of serum concentrations of biomarkers (including cytokines and circulating soluble T1/ST2 receptor) and peripheral blood mononuclear cell expression of T1/ST2 receptor

  Up to 6 months

• Clinical effects of Nerofe on cancer, as assessed by Response Evaluation Criteria in Solid Tumors

  Up to 6 months

• Pharmacokinetic behavior of Nerofe: plasma concentrations in ng/mL

  Pre-dose (Cycle 1 Days 1 and 29 only); and 0.25, 1, 2, 4h, 6, 8, and 24h following the end of infusion (Cycle 1 Days 1 and 29)

• Pharmacokinetic behavior of Nerofe: plasma half-life in minutes

  Cycle 1 Day 1 and Day 29

• Relationship between pretreatment fresh/archival tumor tissue T1/ST2 receptor expression and biological activity of Nerofe

  Up to 6 months

Study Arms (1)

Nerofe

EXPERIMENTAL

Nerofe administered intravenously 3x/week

Drug: Nerofe

Interventions

Nerofe DRUG

Nerofe administered intravenously 3x/week

Also known as: Tumor-Cells Apoptosis Factor

Nerofe

Eligibility Criteria

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

You may qualify if:

• Males and females above 18 years of age.
• Pathologically confirmed locally advanced and/or metastatic solid tumor for which, in the judgment of the Principal Investigator, no standard curative therapy exists.
• Beginning with Cohort 6 of the Dose Escalation Phase and beyond, including the Dose Confirmation Phase, subjects must have 1 of the following solid tumor types: renal cell carcinoma, ovarian carcinoma, triple-negative breast cancer, or metastatic colorectal carcinoma.
• Disease that is evaluable measurable on physical examination or imaging by Response Evaluation Criteria in Solid Tumors (RECIST v1.1 Appendix A), or is characterized by informative tumor marker(s).
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1 (Section 9.1.1.6).
• Acceptable clinical laboratory values at screening, as indicated by:
• Absolute neutrophil count ≥ 1,500/mm3;
• Platelets ≥ 75,000/mm3;
• Total bilirubin ≤ 1.5 × the upper limit of normal (ULN);
• AST (SGOT) ≤ 2.5 × the ULN;
• ALT (SGPT) ≤ 2.5 × the ULN;
• Serum creatinine ≤ 1.5 mg/dL or a measured creatinine clearance ≥ 60 mL/min; and
• Negative serum Beta hCG test in women of childbearing potential (defined as women ≤ 50 years of age or history of amenorrhea for ≤ 12 months prior to study entry).
• Patients with hepatic metastasis are eligible to enroll, provided that the following criteria are met at Screening:
• Total bilirubin is no higher than the ULN;

You may not qualify if:

• Any chemotherapy, immunomodulatory drug therapy, anti-neoplastic hormonal therapy (unless dose has been stable for 3 months prior to Baseline and remains stable during the trial), immunosuppressive therapy, corticosteroids \> 20 mg/day prednisone or equivalent (unless administered to prevent contrast material reactions during radiographic procedures), or growth factor treatment (eg, erythropoietin) within 14 days prior to initiation of study drug.
• Presence of an acute toxicity of prior chemotherapy, with the exception of alopecia or peripheral neuropathy, that has not resolved to ≤ Grade 1, as determined by NCI CTCAE v 4.0 (http://evs.nci.nih.gov/ftp1/CTCAE/About.html).
• Receipt of \>2 prior regimens of cytotoxic chemotherapy, including any use in the neo-adjuvant, adjuvant, and/or metastatic settings.
• Life expectancy \<12 weeks.
• Major surgery or radiation therapy within 28 days prior to initiation of study drug, or highly localized radiation therapy for symptoms control within 14 days of initiation of study drug.
• Receipt of radiotherapy to \>25 % of bone marrow.
• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome-related illness.
• Known active hepatitis B or C or other active liver disease (other than malignancy).
• Active infection requiring systemic therapy.
• Insulin-requiring diabetes mellitus.
• History of any of the following within 12 months prior to initiation of study drug:
• Uncontrolled congestive heart failure (New York Heart Association Classification 3 or 4), unstable angina, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass graft surgery, transient ischemic attack, or pulmonary embolism.
• Uncontrolled arterial hypertension, or anti-hypertensive drugs whose type or dose has been changed within 3 months prior to screening or whose dose is anticipated to change within cycle 1.
• History of syncope, pre-syncope or orthostasis.
• Risk of syncope, in the judgment of the Principal Investigator.

Sponsors & Collaborators

• Immune System Key Ltd: lead

Study Sites (1)

Kaplan Medical Center

Rehovot, 7661041, Israel

Location

Related Publications (1)

• Sandler U, Devary O, Braitbard O, Ohana J, Kass G, Rubinstein AM, Friedman ZY, Devary Y. NEROFE--a novel human hormone-peptide with anti-cancer activity. J Exp Ther Oncol. 2010;8(4):327-39.

  PMID: 21222365 BACKGROUND

Related Links

• Immune System Key Ltd. Website

MeSH Terms

Conditions

Neoplasms

Interventions

tumor-cells apoptosis factor, human

Study Officials

• Yoram Devary, PhD

  Immune System Key Ltd

  STUDY DIRECTOR

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: September 12, 2012
• First Posted: September 24, 2012
• Study Start: December 1, 2013
• Primary Completion: December 19, 2017
• Study Completion: December 19, 2017
• Last Updated: June 25, 2018

Record last verified: 2018-06

Locations

IL (1)