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

This study is currently recruiting participants.
Verified November 2013 by Immune System Key Ltd
Sponsor:
Information provided by (Responsible Party):
Immune System Key Ltd
ClinicalTrials.gov Identifier:
NCT01690741
First received: September 12, 2012
Last updated: November 8, 2013
Last verified: November 2013
  Purpose

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
Cancer
Drug: Nerofe
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
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 ] [ Designated as safety issue: Yes ]

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 ] [ Designated as safety issue: No ]
  • Clinical effects of Nerofe on cancer, as assessed by Response Evaluation Criteria in Solid Tumors [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • Pharmacokinetic behavior of Nerofe: plasma half-life in minutes [ Time Frame: Cycle 1 Day 1 and Day 29 ] [ Designated as safety issue: No ]
  • Relationship between pretreatment fresh/archival tumor tissue T1/ST2 receptor expression and biological activity of Nerofe [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 48
Study Start Date: April 2013
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: June 2014 (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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01690741

Contacts
Contact: Raanan Berger, MD, PhD 972-3-5302290 raanan.berger@sheba.health.gov.il
Contact: Aliza Ackerstein 972-3-5308402 aliza.ackerstein@sheba.health.gov.il

Locations
Israel
Institute of Oncology and Radiotherapy, Cancer Research Center, Chaim Sheba Medical Center Recruiting
Tel Hashomer, Ramat Gan, Israel, 52621
Contact: Raanan Berger, MD, PhD    972-3-5302290    raanan.berger@sheba.health.gov.il   
Contact: Aliza Ackerstein    972-3-5308402    aliza.ackerstein@sheba.health.gov.il   
Principal Investigator: Raanan Berger, MD, PhD         
Sponsors and Collaborators
Immune System Key Ltd
Investigators
Study Director: Yoram Devary, PhD Immune System Key Ltd
  More Information

Additional Information:
Publications:
Responsible Party: Immune System Key Ltd
ClinicalTrials.gov Identifier: NCT01690741     History of Changes
Other Study ID Numbers: ISK-N101
Study First Received: September 12, 2012
Last Updated: November 8, 2013
Health Authority: Israel: Ministry of Health

Keywords provided by Immune System Key Ltd:
Cancer
Malignancy
Solid tumors

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on April 17, 2014