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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2015 by Immune System Key Ltd
Information provided by (Responsible Party):
Immune System Key Ltd Identifier:
First received: September 12, 2012
Last updated: March 23, 2015
Last verified: March 2015
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.

Condition Intervention Phase
Drug: Nerofe
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1, Open-Label, Dose-Escalation Study Evaluating the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Effects of Intravenously Administered Nerofe™ in Subjects With Advanced Malignancies

Resource links provided by NLM:

Further study details as provided by Immune System Key Ltd:

Primary Outcome Measures:
  • Safety, as determined by frequency, nature, and severity of adverse events; and the profile of dose-limiting toxicities [ Time Frame: Up to 6 months ]

Secondary Outcome Measures:
  • 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 [ Time Frame: Up to 6 months ]
  • Clinical effects of Nerofe on cancer, as assessed by Response Evaluation Criteria in Solid Tumors [ Time Frame: Up to 6 months ]
  • Pharmacokinetic behavior of Nerofe: plasma concentrations in ng/mL [ Time Frame: 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 [ Time Frame: Cycle 1 Day 1 and Day 29 ]
  • Relationship between pretreatment fresh/archival tumor tissue T1/ST2 receptor expression and biological activity of Nerofe [ Time Frame: Up to 6 months ]

Estimated Enrollment: 48
Study Start Date: December 2013
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Nerofe
Nerofe administered intravenously 3x/week
Drug: Nerofe
Nerofe administered intravenously 3x/week
Other Name: Tumor-Cells Apoptosis Factor

Detailed Description:
This is a Phase 1 single-center, open-label, non-randomized, dose-escalation study, to be conducted in 2 phases. The Dose Escalation Phase will determine the maximum tolerated dose (MTD) of Nerofe and evaluate its safety and tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary clinical effects. The subsequent Dose Confirmation Phase will be a cohort expansion at or below the MTD of Nerofe. Subjects will be treated with IV doses of Nerofe thrice weekly (on alternating days) in consecutive, 28-day cycles. Subjects will be evaluated regularly for safety. Subjects who tolerate the drug and who do not experience progressive disease, intolerable toxicity, or meet any of the other withdrawal criteria may continue to receive Nerofe for up to 6 cycles, at the discretion of the Principal Investigator. Throughout the trial, oversight will be provided by the Clinical Safety Committee.

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Males and females at least 18 years of age.
  2. Pathologically confirmed locally advanced and/or metastatic solid tumor for which standard therapy proven to provide clinical benefit does not exist, is no longer effective, or cannot be tolerated.
  3. Evaluable disease, either measurable on physical examination or imaging by Response Evaluation Criteria in Solid Tumors, or by informative tumor markers.
  4. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤1.
  5. 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; and
    • Negative serum hCG test in women of childbearing potential.
  6. Willing and able to provide written Informed Consent and comply with the requirements of the study.

Exclusion Criteria:

  1. Any chemotherapy, immunomodulatory drug therapy, anti-neoplastic hormonal therapy (unless dose has been stable for 3 months), immunosuppressive therapy, corticosteroids > 20 mg/day prednisone or equivalent, or growth factor treatment (eg, erythropoietin) within 14 days prior to initiation of study drug.
  2. 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.
  3. Life expectancy <20 weeks.
  4. Major surgery or radiation therapy within 28 days prior to initiation of study drug.
  5. Receipt of radiotherapy to >25 % of bone marrow.
  6. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome-related illness.
  7. Known active hepatitis B or C or other active liver disease (other than malignancy).
  8. Active infection requiring systemic therapy.
  9. Uncontrolled congestive heart failure (New York Heart Association Classification 3 or 4), angina, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass graft surgery, transient ischemic attack, or pulmonary embolism within 3 months prior to initiation of study drug.
  10. 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.
  11. History of pre-syncope or orthostasis.
  12. Risk of syncope, in the judgment of the principle investigator.
  13. History of or ongoing cardiac dysrhythmias requiring treatment, atrial fibrillation of any grade, or persistent prolongation of the QTc (Fridericia) interval to > 450 msec for males or > 470 msec for females.
  14. Pregnant or lactating female.
  15. Any severe, acute, or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01690741

Contact: Salomon Stemmer, MD 972-3-9378005

Rabin Medical Center Recruiting
Petach Tikva, Israel, 49100
Contact: Salomon Stemmer, MD    972-3-9378005   
Principal Investigator: Salomon Stemmer, MD         
Sponsors and Collaborators
Immune System Key Ltd
Study Director: Yoram Devary, PhD Immune System Key Ltd
  More Information

Additional Information:
Responsible Party: Immune System Key Ltd Identifier: NCT01690741     History of Changes
Other Study ID Numbers: ISK-N101 
Study First Received: September 12, 2012
Last Updated: March 23, 2015

Keywords provided by Immune System Key Ltd:
Solid tumors processed this record on January 19, 2017