18F-CP18 Imaging Studies for Cancer Treatment With Birinapant

Brief Title

18F-CP18 Imaging Studies for Cancer Treatment With Birinapant

Official Title

A Pilot Study of [18F]-CP18 PET/CT Imaging in Patients With Relapsed Platinum Resistant or Refractory Epithelial Ovarian Cancer, Primary Peritoneal Cancer or Fallopian Tube Cancer Therapy Receiving Birinapant, a SMAC Mimetic Therapy

Brief Summary

      Background:

      - 18F-CP18 is a chemical designed for use in imaging studies. It is attracted to tumor cells
      that are being killed by cancer treatment. Researchers want to test it in imaging studies for
      people who are being treated with Birinapant. Birinapant is a drug used to treat advanced
      ovarian, fallopian tube, or peritoneal cancers. It works kills tumor cells that have not
      responded to earlier treatment. 18F-CP18 may help to monitor cancer treatments with this
      drug.

      Objectives:

      - To test the effectiveness of 18F-CP18 imaging studies during cancer treatment with
      Birinapant.

      Eligibility:

      - Individuals at least 18 years of age who are taking Birinapant for ovarian, fallopian tube,
      or peritoneal cancer.

      Design:

        -  Participants will have a brief physical exam. They will also answer questions about
           their medical history and any current medications.

        -  Participants will receive a dose of 18F-CP18, followed by an imaging study. The study
           will involve a positron emission tomography/computed tomography (PET/CT) scan. The scan
           will last 40 minutes.

        -  There will be two more PET/CT scans 1 hour and 2 hours after taking 18F-CP18. These
           scans will look at how the tumor cells absorb and process 18F-CP18.

        -  This is a scanning study only. No treatment will be provided as part of this study.

Detailed Description

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.

Study Phase

Phase 2

Study Type

Interventional

Primary Outcome

Tumor Uptake

Condition

Ovarian Neoplasms

Intervention

[18F]-CP18

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status

Drug

Estimated Enrollment

Start Date

November 30, 2012

Completion Date

July 24, 2013

Primary Completion Date

July 24, 2013

Eligibility Criteria

        -  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

Gender

Female

Ages

18 Years - 99 Years

Accepts Healthy Volunteers

No

Contacts

Karen A Kurdziel, M.D., ,

Administrative Informations

NCT ID

NCT01766622

Organization ID

Secondary IDs

13-C-0036

Responsible Party

Sponsor

Study Sponsor

National Institutes of Health Clinical Center (CC)

Collaborators

 National Cancer Institute (NCI)

Study Sponsor

Karen A Kurdziel, M.D., Principal Investigator, National Cancer Institute (NCI)

Verification Date

July 24, 2013