Safety and Efficacy of IV Nerofe™ Followed by Doxorubicin, In Metastatic Ovarian Cancer and Triple Negative Breast Cancer

NCT03634150 | Withdrawn Phase 1 DMC

• 1 other identifier: ISK-N103
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1b, open-label, non-randomized, Dose Confirmation study. Subjects will be treated, once a week, with IV doses of Nerofe and low dose (20 mg/m2) Doxorubicin (6-8 hours from one another) in consecutive, 28-day cycles.

Conditions

Metastatic Ovarian Cancer; Triple Negative Breast Cancer

Outcome Measures

Primary Outcomes (3)

• The primary safety endpoint will be the Adverse Events (AE) reported during the combined treatment of Nerofe and low Dose doxorubicin , using the CTCAE score.

  The Adverse Events (AE) reported during the combined treatment of Nerofe and low Dose doxorubicin, using the CTCAE score.

  Safety data will be collected weekly during the subjects visits(Weeks 1-20), throughout the study and up to 1 year.

• Assessing Change in tumor size from Baseline to End of study

  Assessing Change in tumor size from Baseline to End of study under combined treatment of Nerofe and Low dose Doxorubicin in Ovarian cancer or triple negative breast cancer. Subject population will be evaluated using Response Evaluation Criteria in Solid Tumors, from Baseline, and every 2 cycles( 8 weeks), and last one- at the end of the study.

  Imaging would be performed at Baseline and at the end of every 2 cycles(8 weeks), through the study completion, which is estimated to be after 6 months.

• Assessing Change in Blood markers from Baseline to End of study

  Assessing Change in tumor size from Baseline to End of study, under combined treatment of Nerofe and Low dose Doxorubicin, in Ovarian cancer or triple negative breast cancer. Subject population will be evaluated from Baseline, and every cycle( 28 days each cycle) until the end of the study.

  Blood Markers would be measured at Baseline, and at the end of every cycle(28 Days in each cycle), through the study completion, which is estimated to be after 6 months.

Secondary Outcomes (9)

• Pharmacokinetic Profile

  Pharmacokinetic sampling is planned once at Baseline. In Cycle 1(28 Days in each cycle), and Cycle 2 Day 1 visits: pre-dose and following the end of Nerofe infusion: 15 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, and 24 hours

• Pharmacokinetic Profile

  Pharmacokinetic sampling is planned once at Baseline. In Cycle 1(28 Days in each cycle), and Cycle 2 Day 1 visits: pre-dose and following the end of Nerofe infusion: 15 min ,1 hour, 2 hours, 4 hours, 6 hours, 8 hours, and 24 hours.

• Pharmacokinetic Profile

  Pharmacokinetic sampling is planned once at Baseline. In Cycle 1(28 Days in each cycle), and Cycle 2 Day 1 visits: pre-dose and following the end of Nerofe infusion: 15 min, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, and 24 hours.

• Pharmacokinetic Profile

  Pharmacokinetic sampling is planned once at Baseline. In Cycle 1(28 Days in each cycle), and Cycle 2 Day 1 visits: pre-dose and following the end of Nerofe infusion: 15 min, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, and 24 hours.

• Pharmacokinetic Profile

  Pharmacokinetic sampling is planned once at Baseline. In Cycle 1(28 Days in each cycle), and Cycle 2 Day 1 visits: pre-dose and following the end of Nerofe infusion: 15 min, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, and 24 hours.

Study Arms (1)

Single arm Nerofe followed by Doxorubicin

EXPERIMENTAL

IV treatment of Nerofe 96 mg\\m2 followed by IV Doxorubicin 10mg\\m2 Once weekly

Biological: Nerofe is a first in class derivative of a human hormon-peptide(TCApF), with Cancer suppressive properties.

Interventions

Nerofe is a first in class derivative of a human hormon-peptide(TCApF), with Cancer suppressive properties. BIOLOGICAL

Once weekly treatment, with IV doses of Nerofe (96mg\\m2) and low dose (20 mg/m2) Doxorubicin 5 or 24 hours from one another) .

Also known as: Doxorubicin or Adriamycin is a registered chemotherapy, which belongs to the Anthracyclines. It slows or stops the growth of cancer cells.

Single arm Nerofe followed by Doxorubicin

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Females over18 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.
• Subjects must have 1 of the following solid tumor types: Ovarian cancer (up to 12 patients), or by Triple-negative breast cancer (up to 12 patients).
• Disease that is evaluable, or measurable on imaging by Response Evaluation Criteria in Solid Tumors (RECIST v1.1 Appendix A), and where applicable is characterized by informative tumor marker(s).
• Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2(Section 6.1.1.6) .
• Acceptable clinical laboratory values at screening, as indicated by:
• Absolute neutrophil count ≥ 1,500/mm3; Platelets ≥ 75,000/mm3; Total bilirubin ≤ 5 mg/dL. ASpartate aminoTransferase (SGOT) ≤ 2.5 × the Upper Limit of Normal; ALalanine aminoTransferase (SGPT) ≤ 2.5 × the Upper Limit of Normal; Serum creatinine ≤ 1.5 mg/dL or a measured creatinine clearance higher than 60 mL/min; and Negative serum Beta human chorionic gonadotropin 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 ≤ 5 \* mg/dL; ASpartate aminoTransferase and ALalanine aminoTransferase are each ≤ 5 × the Upper Limit of Normal;
• Willing and able to provide written Informed Consent and comply with the requirements of the study.
• Tumor tissue, taken from either an archival sample or a fresh biopsy, must be available for staining for T1/ST2 receptor, and must be ST2 positive.
• Subject has not been previously treated with Doxorubicin or total accumulated dose has never exceeded 240 mg/m2.

You may not qualify if:

• Any chemotherapy, immunomodulatory drug therapy, anti-neoplastic hormonal therapy (unless dose has been stable for 1 month 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 \>3 prior regimens of cytotoxic chemotherapy, including any use in the neo-adjuvant, adjuvant, and/or metastatic settings ,Unless more than 1 year elapsed since the Neo-adjuvant treatment was completed
• Receipt of Blood Transfusion during 2 weeks prior to Baseline
• Life expectancy \<12 weeks.
• Major surgery or radiation therapy within 28 days prior to initiation of study drug,
• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome-related illness.
• Patients with history of brain metastasis
• Known active hepatitis B or C or other active liver disease (other than malignancy).
• Severe liver dysfunction (Child-Pugh Class B or C) and
• Patients with a history of esophageal bleeding have varices that have been sclerosed or banded and no bleeding episodes have occurred during the prior 6 months.
• Active infection requiring systemic therapy.
• Insulin-requiring diabetes mellitus will not be included if, according to the investigator, not stable, during the last 6 months.
• 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 (within the last 6 months). Left Ventricular Ejection Fraction \<50% .

Sponsors & Collaborators

• Immune System Key Ltd: lead

Study Sites (1)

Oncologic Institue, Kaplan

Rehovot, 7661041, Israel

Location

Related Publications (1)

• Stemmer SM, Benjaminov O, Silverman MH, Sandler U, Purim O, Sender N, Meir C, Oren-Apoteker P, Ohana J, Devary Y. A phase I clinical trial of dTCApFs, a derivative of a novel human hormone peptide, for the treatment of advanced/metastatic solid tumors. Mol Clin Oncol. 2018 Jan;8(1):22-29. doi: 10.3892/mco.2017.1505. Epub 2017 Nov 15.

  PMID: 29423221 RESULT

MeSH Terms

Conditions

Ovarian Neoplasms; Triple Negative Breast Neoplasms

Interventions

Doxorubicin

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Breast Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

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

Model Details: Experimental: IV Nerofe 96 mg\\m2 followed by IV Doxorubicin 10mg\\m2, once weekly

Study Record Dates

• First Submitted: June 20, 2018
• First Posted: August 16, 2018
• Study Start: September 6, 2018
• Primary Completion: April 21, 2020
• Study Completion: April 21, 2020
• Last Updated: October 26, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1)