Protocol Number: 09-C-0174

Title:

M06-822: A Phase 1/2a Study Evaluating the Safety, Pharmacokinetics, and Efficacy of ABT-263 in Subjects with Small Cell Lung Cancer or Other Non-Hematological Malignancies

Number:

09-C-0174

Summary:

BACKGROUND:

-Bcl-2 family of proteins are regulators of the intrinsic apoptosis pathway

-ABT-263 is a small molecule Bcl-2 family protein inhibitor that binds with high affinity to multiple anti-apoptotic Bcl-2 family proteins including Bcl- XL, Bcl-2, Bcl-w, BclB.

-B-cell lymphomas and small cell lung cancer highly express Bcl-2 and are exquisitely sensitive in vitro and in vivo to the compound.

OBJECTIVES:

Phase 2A Objectives

-Safety assessment at the recommended Phase 2 dose

-Preliminary efficacy assessment

ELIGIBILITY:

Phase 2A

-Histologically documented SCLC measurable by RECIST

-Chemotherapy naive extensive stage SCLC or the subject has received at least one chemotherapy treatment regimen and has experienced progressive disease following treatment, or their disease is refractory

-Patients with brain metastases must have clinically controlled neurologic symptoms defined by surgical excision and or radiation, therapy followed by 21 days of stable neurologic function

-Female subjects must be surgically sterile, postmenopausal or have a negative pregnancy test. Females who are not surgically sterile or postmenopausal and all non-vasectomized male subjects must agree to an approved birth control (double barrier or hormonal contraceptives)

-greater than or equal to 18 years of age; ECOG 51

-Subjects receiving Selective Serotonin Reuptake Inhibitor (SSRI) antidepressants (e.g., Prozac) must be receiving a stable dose for at least 21 days

-Patients should have adequate liver, renal, and bone marrow function, and adequate coagulation parameters

-Patients with active peptic ulcer disease or other potentially hemorrhagic esophagitis/gastritis will be excluded

-Patients may not have received chemotherapy, radiation, hormonal, biologic or other investigational therapy within 14 days of first dose of study drug. Subject must have recovered to less than a grade 2 clinically significant adverse events.

-The subject must have archived diagnostic tissue available for assessment of Bcl-2 family protein expression.

-Patient must sign informed consent.

STUDY DESIGN:

-ABT-263 will be administered orally for 14 consecutive days followed by 7 days off drug. All subjects will self-administer ABT-263 at approximately 30 minutes after breakfast

-40 patients will be entered in to the Phase 2A portion of the study at all sites. The CCR will enter 10 patients on to study.

-Blood will be collected for pharmacogenetics, proteomics, serum markers ProGRP and M30IM65, and circulating tumor cells in consenting patients only.

-Blood screening tests will be obtain within 14 days of drug administration; imaging will be performed within 21 days of drug administration.

-Lymphocyte enumeration with be performed at screening, on day 14 of cycle 1,after cycle 4 and every 3 cycles thereafter and at final visit.

-Pharmacokinetics will be collected on cycle 1 day 14, pre dose and 4 hours post dose.

-IHC and FISH will be performed on tissue slides from archived, diagnostic, formalin fixed paraffin embedded tissue blocks for all patients

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

ELIGIBILITY CRITERIA:

Histologically documented SCLC measurable by RECIST

Chemotherapy naive extensive stage SCLC or the subject has received at least one chemotherapy treatment regimen and has experienced progressive disease following treatment, or their disease is refractory.

Patients with brain metastases must have clinically controlled neurologic symptoms defined by surgical excision and or radiation therapy followed by 21 days of stable neurologic function.

Female subjects must be surgically sterile, postmenopausal or have a negative pregnancy test. Females who are not surgically sterile or postmenopausal and all non-vasectomized male subjects must agree to an approved birth control (double barrier or hormonal contraceptives).

Greater than or equal to 18 years of age; ECOG less than or equal to 1

Subjects receiving Selective Serotonin Reuptake Inhibitor (SSRI) antidepressants (e.g., Prozac) must be receiving a stable dose for at least 21 days.

Patients should have adequate liver, renal, and bone marrow function, and adequate coagulation parameters.

Patients with active peptic ulcer disease or other potentially hemorrhagic esophagitis/gastritis will be excluded.

Patients may not have received chemotherapy, radiation, hormonal, biologic or other investigational therapy within 14 days of first dose of study drug. Subject must have recovered to less than a grade 2 clinically significant adverse events.

The subject must have archived diagnostic tissue available for assessment of Bcl-2 family protein expression.

Patient must sign informed consent.

Special Instructions:

Currently Not Provided

Keywords:

BCL-2

Apoptosis

Recruitment Keyword(s):

Small Cell Lung Cancer

Condition(s):

SCLC

Investigational Drug(s):

ABT-263

Investigational Device(s):

None

Intervention(s):

Drug: ABT-263

Supporting Site:

National Cancer Institute

Contact(s):

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office
Phone: 1-888-NCI-1937
Fax: Not Listed
Electronic Address: ncicssc@mail.nih.gov

Citation(s):

Korsmeyer SJ. BCL-2 gene family and the regulation of programmed cell death. Cancer Res. 1999 Apr 1;59(7 Suppl):1693s-1700s.

Cory S, Adams JM. The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer. 2002 Sep;2(9):647-56.

Borner C. The Bcl-2 protein family: sensors and checkpoints for life-or-death decisions. Mol Immunol. 2003 Jan;39(11):615-47.

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department of Clinical Research Informatics, CC.

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