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

Ovary Cancer Clinical Trial

Official title: An Exploratory, Open-label Study of the Folic Acid-tubulysin Conjugate EC1456 in Ovarian Cancer Subjects Undergoing Cytoreductive Surgery

Status Completed

Clinical Trial 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.

Clinical Trial Description

Study EC1456-02 is an exploratory, open-label study that seeks to enroll subjects with ovarian cancer who will be undergoing therapeutic debulking surgery.

All subjects will undergo a 99mTc-etarfolatide scan within 2 weeks prior to EC1456 administration. Briefly, prior to the 99mTc-etarfolatide imaging procedure, all subjects will receive one intravenous (IV) injection of folic acid or unlabeled etarfolatide, followed within 1 to 3 minutes by an injection of 99m Tc-etarfolatide (i.e., etarfolatide labeled with 740 to 925 megabecquerels (MBq) [20 to 25 millicuries (mCi)] of sodium pertechnetate Tc-99m injection).

Individual subjects will receive 1 of the following 2 doses of EC1456 pre-operatively:

• 4 milligrams (mg)/meter (m)2

• 8 milligrams (mg)/meter (m)2

EC1456 will be administered at 1 of the following 2 time points:

• <8 hours before planned surgery

• 48±4 hours before planned surgery

The 4 mg/m2 dose of EC1456 administered <8 hours prior to surgery will be the first dose cohort to enroll. Once enrollment to this cohort is complete, the remaining cohorts will be open for enrollment. Assignment to specific cohorts will be determined by the Sponsor based on data assessed from previously enrolled subjects. Two to six subjects will be enrolled per cohort as shown below.

• Cohort 1: 4 mg/m2 EC1456 <8 hours prior to surgery

• Cohort 2: 4 mg/m2 EC1456 48±4 hours prior to surgery

• Cohort 3: 8 mg/m2 EC1456 <8 hours prior to surgery

• Cohort 4: 8 mg/m2 EC1456 48±4 hours prior to surgery

In the event of unexpected results, lower, intermediate or higher EC1456 levels up to 12.5 mg/m2, the highest determined safe dose of EC1456 as defined by the parallel phase I study EC1456-01, may be explored.

The first on-study procedure will be SPECT or SPECT/CT with 99mTc-etarfolatide. SPECT or SPECT/CT scans will be acquired within 2 weeks prior to EC1456 administration as specified in the Imaging Operations Manual.

EC1456 will be administered pre-operatively as an intravenous (IV) bolus infusion at 1 of 2 time points:

1. < 8 hours preceding surgery or

2. 48±4 hours preceding surgery.

At 2 time points:

1. within approximately 15 (±5) minutes post-EC1456 administration and

2. at the start of surgery, approximately 5 mL of whole blood will be drawn for EC1456 analyses.

Tissues to be collected at surgery, if present, include: sample of 1 or both ovaries, endometrium, omentum, ascitic fluid and/or selected lesions as identified by the surgeon or sponsor. The location of each sample will be annotated such that the ex vivo analysis may be correlated with the SPECT/CT image post-surgery. Samples of tumor tissue will be collected at the time of surgery, aliquoted into collection vials, and placed on dry ice or in buffered formalin. ;

Related Conditions & MeSH terms

• Ovarian Neoplasms
• Ovary Cancer

• NCT number: NCT03011320
• Study type: Interventional
• Source: Endocyte
• Status: Completed
• Phase: Phase 1
• Start date: January 24, 2017
• Completion date: August 28, 2018