An Exploratory Study of the Folic Acid-tubulysin Conjugate EC1456 in Ovarian Cancer Subjects Undergoing Surgery

• Status: Completed
• Trial end date: 2018-08-28
• Target enrollment: 0
• Participant gender: Female

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Endocyte
• Treatments: Folic Acid; Sodium Pertechnetate Tc 99m; Vitamin B Complex

Criteria

Inclusion Criteria:

1. Subject must have the ability to understand, and have signed an approved informed consent form (ICF).

2. 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.

3. Subject must be ≥18 years of age.

4. Subject must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

5. 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.

6. 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.

7. 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.

• Hepatic:

• Total bilirubin ≤1.5 × the upper limit of normal (ULN).

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST

• 3.0 × ULN, or ≤5.0 × ULN for subjects with liver metastases.

• Renal: Serum creatinine ≤1.5 × ULN, or for subjects with serum creatinine >1.5 × ULN, creatinine clearance ≥50 mL/min.

8. Subjects of childbearing potential:

• All women of childbearing potential MUST have a negative urine or serum pregnancy test within 1 week prior to the 99mTc-etarfolatide imaging procedure and within 1 week prior to the dose of EC1456.

• Women of childbearing potential must practice an effective method of birth control (e.g., oral, transdermal or injectable contraceptives, intrauterine device [IUD], or double-barrier contraception, such as diaphragm and spermicidal jelly) for the duration of their participation in

Exclusion Criteria:

1. 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).

2. Use of the following medications within 6 months prior to EC1456 administration:

amiodarone, disopyramide, dofetilide, dronedarone, flecanamide, ibutilide, quinidine, or sotalol.

3. 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).

4. Subject has known active hepatitis B or hepatitis C.

5. Subject has active uncontrolled infection(s).