NCT03011320

Brief Summary

This study looks to enroll subjects with ovarian cancer who will be having standard of care surgery to remove ovarian cancer tumors. The main aim of this study is to be able to observe how EC1456 has been taken in and broken down inside tumors. The effect of EC1456 on the tumor will also be studied. This study will also help us compare the amount of EC1456 seen in tumors and how the tumors are imaged by the 99mTc-etarfolatide single-photon emission tomography (SPECT) or single-photon emission tomography with in-line x-ray computed tomography (SPECT/CT). All subjects will undergo a 99mTc-etarfolatide SPECT or SPECT/CT scan within 2 weeks prior to EC1456 administration. Individual subjects will then receive 1 of the following 2 doses of EC1456 pre-operatively:

  • 4 mg/m2
  • 8 mg/m2 EC1456 will be administered at 1 of the following 2 time points:
  • \<8 hours before planned surgery
  • 48±4 hours before planned surgery Blood will be collected for pharmacokinetic (PK) studies right after EC1456 dosing and again right before surgery. At the time of surgery, tumor samples will be removed and sent to Endocyte for analysis.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
3

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Jan 2017

Geographic Reach
2 countries

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 19, 2016

Completed
17 days until next milestone

First Posted

Study publicly available on registry

January 5, 2017

Completed
19 days until next milestone

Study Start

First participant enrolled

January 24, 2017

Completed
11 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 30, 2017

Completed
8 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 28, 2018

Completed
Last Updated

February 7, 2019

Status Verified

February 1, 2019

Enrollment Period

11 months

First QC Date

December 19, 2016

Last Update Submit

February 6, 2019

Conditions

Ovary Cancer

Keywords

ovarian cancerspecimen collection

Outcome Measures

Primary Outcomes (1)

  • To assess tumor penetration of EC1456 in frozen tissue

    Measure and characterize intratumoral levels of EC1456, and metabolites, by liquid chromatography-tandem mass spectrometry (LC-MS/MS). All results will be descriptive and exploratory.

    18 months

Secondary Outcomes (2)

  • To assess tumor penetration EC1456 in formalin fixed tissue samples (intratumoral levels of EC1456 in tissue blocks using anti-tubulysin IHC testing)

    18 months

  • To assess correlation of tumor penetration of EC1456 with tumor uptake of 99m-Tc etarfolatide in SPECT or SPECT/CT scan

    18 month

Study Arms (4)

Cohort 1

EXPERIMENTAL

Injection of unlabeled etarfolatide followed by etarfolatide labeled with 740 to 925 megabecquerels (MBq) \[20 to 25 millicuries (mCi)\] of sodium pertechnetate Tc-99m injection, followed by a single-photon emission tomography (SPECT) or single-photon emission tomography with in-line x-ray computed tomography (SPECT/CT) scan. One dose of 4 mg/m2 EC1456 at \<8 hours prior to surgery

Drug: EC1456Drug: 99mTc-Etarfolatide

Cohort 2

EXPERIMENTAL

Injection of unlabeled etarfolatide followed by etarfolatide labeled with 740 to 925 megabecquerels (MBq) \[20 to 25 millicuries (mCi)\] of sodium pertechnetate Tc-99m injection, followed by a single-photon emission tomography (SPECT) or single-photon emission tomography with in-line x-ray computed tomography (SPECT/CT) scan. One dose of 4 mg/m2 EC1456 at 48±4 hours prior to surgery

Drug: EC1456Drug: 99mTc-Etarfolatide

Cohort 3

EXPERIMENTAL

Injection of unlabeled etarfolatide followed by etarfolatide labeled with 740 to 925 megabecquerels (MBq) \[20 to 25 millicuries (mCi)\] of sodium pertechnetate Tc-99m injection, followed by a single-photon emission tomography (SPECT) or single-photon emission tomography with in-line x-ray computed tomography (SPECT/CT) scan. One dose of 8 mg/m2 EC1456 at \<8 hours prior to surgery

Drug: EC1456Drug: 99mTc-Etarfolatide

Cohort 4

EXPERIMENTAL

Injection of unlabeled etarfolatide followed by etarfolatide labeled with 740 to 925 megabecquerels (MBq) \[20 to 25 millicuries (mCi)\] of sodium pertechnetate Tc-99m injection, followed by a single-photon emission tomography (SPECT) or single-photon emission tomography with in-line x-ray computed tomography (SPECT/CT) scan. One dose of 8 mg/m2 EC1456 at 48±4 hours prior to surgery

Drug: EC1456Drug: 99mTc-Etarfolatide

Interventions

EC1456DRUG

intravenous (IV) bolus dose

Also known as: folate (vitamin B-9) and tubulysin B hydrazide small molecule conjugate
Cohort 1Cohort 2Cohort 3Cohort 4
99mTc-EtarfolatideDRUG

Injection of unlabeled etarfolatide followed by etarfolatide labeled with 740 to 925 megabecquerels (MBq) \[20 to 25 millicuries (mCi)\] of sodium pertechnetate Tc-99m injection, followed by a single-photon emission tomography (SPECT) or single-photon emission tomography with in-line x-ray computed tomography (SPECT/CT) scan.

Also known as: EC20, etarfolatide
Cohort 1Cohort 2Cohort 3Cohort 4

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Subject must have the ability to understand, and have signed an approved informed consent form (ICF).
  • Subjects must have cytologically or pathologically confirmed advanced ovarian cancer and be scheduled for primary, interval, or secondary, cytoreductive surgery as a part of standard of care for treatment of ovarian cancer, and have at least 1 lesion that can be removed at surgery.
  • Subject must be ≥18 years of age.
  • Subject must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Subjects with central nervous system (CNS) metastases must be neurologically stable and off of steroids for at least 14 days before pre-registration. Subjects with asymptomatic CNS metastatic disease without associated edema, shift, and a requirement for steroids or anti-seizure medications may be eligible after discussion with the sponsor's medical monitor.
  • Subjects must have recovered (to baseline/ stabilization) from prior chemo- or radiotherapy and associated acute toxicities must have resolved to a NCI CTCAE v4 Grade 1 or less, with the exception of alopecia.
  • Subject must have adequate organ function:
  • Bone marrow reserve:
  • Absolute neutrophil count ≥1.5 × 109/L.
  • Platelets ≥100 × 109/L.
  • Hemoglobin ≥9 g/dL.
  • Cardiac:
  • Left ventricular ejection fraction (LVEF) ≥ the institutional lower limit of normal. LVEF must be evaluated within 28 days prior to the dose of EC1456.
  • Cardiac Troponin I within normal limits.
  • Electrocardiogram QT segment corrected by the method of Fridericia QTcFridericia (QTcF) \< 450 msec on at least 2 of 3 screening ECG's. On site determination of QTcF may be used for screening purposes.
  • +8 more criteria

You may not qualify if:

  • In the opinion of the investigator, a subject's physical condition might create a hardship for tolerating the radionuclide imaging procedures or a single administration of EC1456 (e.g., due to pain or dyspnea in prolonged supine positions).
  • Use of the following medications within 6 months prior to EC1456 administration: amiodarone, disopyramide, dofetilide, dronedarone, flecanamide, ibutilide, quinidine, or sotalol.
  • Subject has a co-morbid medical condition that, in the opinion of the investigator, is known to have a major impact on the pharmacokinetics (PK), distribution, metabolism, or elimination of either small molecule drug conjugate (SMDC).
  • Subject has known active hepatitis B or hepatitis C.
  • Subject has active uncontrolled infection(s).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Levine Cancer Institute-Concord/Clinical Trials

Concord, North Carolina, 28025, United States

Location

Ottawa Hospital

Ottawa, Ontario, K1H 8L6, Canada

Location

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

Folic AcidLeucovorintechnetium 99m etarfolatide

Condition Hierarchy (Ancestors)

Endocrine Gland NeoplasmsNeoplasms by SiteNeoplasmsOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital Neoplasms, FemaleUrogenital NeoplasmsGenital DiseasesEndocrine System DiseasesGonadal Disorders

Intervention Hierarchy (Ancestors)

PterinsPteridinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsFormyltetrahydrofolatesTetrahydrofolatesCoenzymesEnzymes and Coenzymes

Study Officials

  • Alison Armour, MB ChB, BSc, MSc, MD, MRCP

    Endocyte

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 19, 2016

First Posted

January 5, 2017

Study Start

January 24, 2017

Primary Completion

December 30, 2017

Study Completion

August 28, 2018

Last Updated

February 7, 2019

Record last verified: 2019-02

Data Sharing

IPD Sharing
Will not share

Locations

US(1)CA(1)