- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01690741
Phase 1 Trial of Intravenously Administered Nerofe™ in Subjects With Advanced Malignancies
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
Study Overview
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
-
Rehovot, Israel, 7661041
- Kaplan Medical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Subjects must meet all of the following inclusion criteria to be eligible for the study:
- 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;
- AST and ALT are each ≤ 5 × the ULN;
- Severe liver dysfunction (Child-Pugh Class B or C) is not present; 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.
- If there is a history of brain metastasis treated with radiation therapy, the radiation therapy must have been completed at least 4 weeks prior to enrollment, the metastatic disease must have been stable since completion, and the subject maybe taking no more than 4 mg/day of dexamethasone
- Willing and able to provide written Informed Consent and comply with the requirements of the study.
- Beginning with Cohort 5 of the Dose Escalation Phase: Tumor tissue, taken from either an archival sample or a fresh biopsy, must be available for staining for T1/ST2 receptor (see Sections 8.2.1 and 8.2.3).
- In the Dose Confirmation Phase only, subjects must have disease that is measurable on physical examination or imaging by RECIST v1.1 (Appendix A).
Exclusion Criteria:
- 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.
- 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.
- Previous malignancy, except for intraepithelial neoplasia; basal cell carcinoma of the skin; adequately treated localized prostate carcinoma with current Prostate-Specific Antigen <1.0 ng/mL; a history of potentially curative therapy with no evidence recurrence for at least 2 years; or a previously treated malignancy within the past 2 years that the Principal Investigator deems to be at low risk for recurrence during the course of this trial.
- Use of any investigational agents within a minimum of 3 weeks or 5 half-lives of initiation of study drug.
- Pregnant or lactating female.
- Women of childbearing potential, unless they agree to use dual contraceptive methods which, in the opinion of the Principal Investigator, are effective and adequate for that patient's circumstances while on study drug and for 3 months afterward.
- Men who partner with a woman of childbearing potential, unless they agree to use effective, dual contraceptive methods (ie, a condom, with female partner using oral, injectable, or barrier method) while on study drug and for 3 months afterward.
- Any severe, acute, or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, may interfere with the informed consent process and/or with compliance with the requirements of the study, or may interfere with the interpretation of study results and, in the investigator's opinion, would make the patient inappropriate for entry into this study.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Nerofe
Nerofe administered intravenously 3x/week
|
Nerofe administered intravenously 3x/week
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Safety, as determined by frequency, nature, and severity of adverse events; and the profile of dose-limiting toxicities
Time Frame: Up to 6 months
|
Up to 6 months
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
|
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
|
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)
|
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
|
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
|
Up to 6 months
|
Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
Helpful Links
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- ISK-N101
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Cancer
-
University of Michigan Rogel Cancer CenterRecruitingCancer Liver | Cancer Brain | Cancer Head &Neck | Cancer PelvisUnited States
-
Cellworks Group Inc.RecruitingCancer | Relapsed Cancer | Refractory CancerUnited States
-
UNC Lineberger Comprehensive Cancer CenterHyundai Hope On WheelsRecruitingCancer | Pediatric Cancer | Survivorship | Cancer MetastaticUnited States
-
Vanderbilt-Ingram Cancer CenterNational Institutes of Health (NIH)Active, not recruitingAdvanced Cancer | Relapsed Cancer | Refractory CancerUnited States
-
City of Hope Medical CenterNational Cancer Institute (NCI)CompletedStage III Pancreatic Cancer | Stage IIA Pancreatic Cancer | Stage IIB Pancreatic Cancer | Stage IV Gastric Cancer | Stage IVA Colorectal Cancer | Stage IVA Pancreatic Cancer | Stage IVB Colorectal Cancer | Stage IVB Pancreatic Cancer | Stage IIIA Gastric Cancer | Stage IIIB Gastric Cancer | Stage IIIC Gastric... and other conditionsUnited States
-
MiRXES Pte LtdRecruitingBreast Cancer | Gastric Cancer | Colorectal Cancer | Pancreatic Cancer | Esophageal Cancer | Ovarian Cancer | Prostate Cancer | Thoracic Cancer | Liver CancerSingapore
-
Sidney Kimmel Cancer Center at Thomas Jefferson...CompletedStage I Breast Cancer | Stage I Uterine Corpus Cancer | Stage II Uterine Corpus Cancer | Stage III Uterine Corpus Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIA Breast Cancer | Stage IIB Breast Cancer | Stage... and other conditionsUnited States
-
Massachusetts General HospitalNational Comprehensive Cancer NetworkCompletedGastric Cancer | Pancreatic Cancer | Esophageal Cancer | Rectal Cancer | Colon Cancer | Hepatobiliary CancerUnited States
-
University of California, San FranciscoBristol-Myers Squibb; PfizerTerminatedStage IIIA Rectal Cancer | Stage IIIB Rectal Cancer | Stage IIIC Rectal Cancer | Metastatic Colorectal Adenocarcinoma | Metastatic Colon Adenocarcinoma | Metastatic Rectal Adenocarcinoma | Stage IIIA Colon Cancer | Stage IIIB Colon Cancer | Stage IIIC Colon Cancer | Stage IV Colon Cancer | Stage IV Rectal... and other conditionsUnited States
-
Johns Hopkins UniversityNational Cancer Institute (NCI); National Institute on Minority Health and...Enrolling by invitationCancer | Advanced Cancer | End Stage Cancer | MalignancyUnited States
Clinical Trials on Nerofe
-
Immune System Key LtdUniversity of Miami Sylvester Comprehensive Cancer CenterRecruitingAML | Advanced MDSUnited States
-
VastBiomeRecruitingRenal Cell Carcinoma | Non-Small-Cell Lung Carcinoma | Malignant Melanoma | Triple-Negative Breast CancerUnited States
-
Immune System Key LtdWithdrawnMyelodysplastic Syndromes | Acute Myelogenous LeukemiaIsrael
-
Georgetown UniversityImmune System Key LtdRecruitingSolid Tumor | KRAS Mutation-Related TumorsUnited States
-
University of British ColumbiaCompleted
-
Immune System Key LtdWithdrawnTriple Negative Breast Cancer | Metastatic Ovarian CancerIsrael