18F-CP18 Imaging Studies for Cancer Treatment With Birinapant

Background:

Dysregulation of apoptosis is instrumental in forming the malignant phenotype and is
associated with resistance to chemotherapeutics and biological therapies. Cleaved Caspase 3
(its activated form) plays a key role in the common apoptotic pathway.

CP18 is an enzyme substrate of caspase 3. The formulation [18F]-CP18 includes PEG vector
which facilitates internalization and can be non-invasively imaged using PET. Once cleaved
into polar fragments by caspase 3, it become trapped within the cells.

In a phase 2 NCI clinical trial (NCI Protocol (#12C0191) CTEP 9235), Birinapant (TL32711), a
SMAC (second mitochondrial derived activator of caspase) mimetic, is being evaluated in
patients with relapsed platinum resistant or refractory epithelial ovarian cancer, primary
peritoneal cancer or fallopian tube cancer.

PET/CT imaging with [18F]-CP18 may enable the non-invasive, in vivo monitoring of this drugs
pro-apoptotic effects. If a measureable effect is shown in this pilot study, further
evaluation of [18F]-CP18 PET/CT's potential to monitor apoptosis may be warranted.

Primary Objective:

To determine tumor uptake and retention of [18F]-CP18 before and after treatment with a SMAC
mimetic (Birinapant, TL32711), in patients with relapsed platinum resistant or refractory
epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer.

Eligibility:

All subjects must meet the eligibility criteria for the phase 2 study of Birinapant (NCI
Protocol (#12C0191) CTEP 9235) and be enrolled in or planning to enroll in parent therapy
protocol

All subjects must sign a document of informed consent indicating their understanding of the
investigational nature and risks of the study before any protocol related studies are
performed.

Design:

This is a pilot study to assess the change in [18F]-CP18 PET tumor uptake following
treatment with Birinapant, a SMAC mimetic drug, in patients with relapsed platinum resistant
or refractory epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer.
Subjects will undergo at least 3 [18F]-CP18 PET/CT imaging studies,one pre-therapy, one
within 48 hours after receiving the initial dose of Birinapant, and a third scan within 48
hours after receiving cycle 2, day 15 dose of Birinapant and prior to the tumor biopsy on
the same day. An exploration of the relationship between PET imaging parameters and clinical
response and various biomarkers (as determined under the referring protocol) will also be
performed. Ten patients will be enrolled on this protocol.

- INCLUSION CRITERIA

Subjects with pathology proven epithelial ovarian cancer, primary peritoneal cancer or
fallopian tube cancer that are relapsed or refractory to prior platinum-based standard
care systemic regimen, enrolled, or eligible to be enrolled in the Phase 2 NCI protocol
treatment using Birinapant (NCI Protocol (#12C0191)CTEP 9235); therefore must meet the
inclusion criteria for that study

Ability to provide informed consent. All patients must sign a document of informed consent
indicating their understanding of the investigational nature and risks of this study
before any protocol related studies are performed.

EXCLUSION CRITERIA

Known allergy to any of the formulation components of [18F]-CP18.

The subject is pregnant or nursing

Participants for whom enrollment would significantly delay (> 2 weeks) the scheduled
standard of care therapy.

Participants with any coexisting medical or psychiatric condition that is likely to
interfere with study procedures and/or results are excluded.

Participants with severe claustrophobia not relieved by oral anxiolytic medication or
patients weighing > 136 kg (weight limit for scanner table).

Other medical conditions deemed by the PI or associates to make the patient ineligible for
protocol procedures.

It is likely that all patients in this study will be surgically sterile. If this is not
the case, the patient must have a negative serum beta HCG within 24 hour prior to PET/CT
or be post-menopausal for greater than or equal to 2 years