A Phase 1/2a Study of ABT-263 in Subjects With Small Cell Lung Cancer (SCLC) or Other Non-Hematological Malignancies

Small Cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00445198
• Other study ID #: M06-822
• Secondary ID: 2006-003298-28
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: April 2007
• Est. completion date: December 2010

Study information

• Verified date: January 2013
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The Phase 1 portion of the study will evaluate the pharmacokinetic profile and safety of ABT-263 with the objective of defining the dose limiting toxicity and maximum tolerated dose. (This portion of the study is complete). The Phase 2a portion of the study will evaluate ABT-263 at the defined recommended Phase 2 dose to obtain additional safety information and a preliminary assessment of efficacy.

Other known NCT identifiers

• NCT00929513

Recruitment information / eligibility

• Status: Completed
• Enrollment: 86
• Est. completion date: December 2010
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• The subject must be >=18 years of age.(Phase 1 & 2a)

• Histologically and/or cytologically documented diagnosis of small cell lung cancer (North America & UK) or other non-hematological malignancy (North America only).(Phase 1 only)

• Histologically and/or cytologically documented diagnosis of SCLC.(Phase 2a)

• At least one prior chemotherapy treatment regimen(s) and their disease is refractory or experienced progressive disease following the treatment.(Phase 1)

• Extensive-stage SCLC & is chemotherapy naïve(US only) has experienced progressive disease following at least one chemotherapy regimen or their disease is refractory.(Phase 2a)

• Brain metastases with clinically controlled neurologic symptoms, defined as surgical excision and/or radiation therapy followed by 21 days of stable neurologic function & no evidence of CNS disease progression as determined by CT or MRI within 21 days prior to the first dose of study drug.

• ECOG performance score <= 2(Ph 1) <=1(Phase 2a)

• Must be receiving a stable dose of Selective Serotonin Reuptake Inhibitor (SSRI) anti-depressants 21 days prior to 1st dose of study drug.

• Adequate bone marrow, renal & hepatic function per local lab reference range at Screening as follows:

• Bone marrow: Absolute Neutrophil count (ANC)>=1000/µL

• Platelets>= 100,000/mm3

• Hemoglobin>=9.0g/dL

• Renal function: Serum creatinine<= 2.0mg/dL or calculated creatinine clearance>=50mL/min

• Hepatic function&enzymes: AST and ALT<=3.0 x the upper normal limit(ULN) of institution's normal range

• Bilirubin<=1.5xULN. If Gilbert's Syndrome may have Bilirubin> 1.5 x ULN

• Coagulation: aPTT and PT<=1.2 x the upper limit of normal

• Should have archived diagnostic tissue available for assessment of Bcl-2 family protein expression.(Phase 2a)

• All female subjects not surgically sterile or postmenopausal(for at least 1 year)and non-vasectomized male subject must practice at least one method of birth control.

Exclusion Criteria:

• Underlying or predisposing condition of bleeding or currently exhibits signs of bleeding.

• Recent history of non-chemotherapy induced thrombocytopenia associated bleeding within 1 year prior to first dose of study drug.

• Active peptic ulcer disease or other potentially hemorrhagic esophagitis/gastritis.

• The subject has active immune thrombocytopenic purpura (ITP),active autoimmune hemolytic anemia (AIHA), or a history of being refractory to platelet transfusions (within 1 year prior to the first dose of study drug).

• Currently receiving or requires anticoagulation therapy or any drug or herbal supplements that affect platelet function, with exception of low-dose anticoagulation medications that are used to maintain the patency of a central intravenous catheter.

• Received any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, hormonal (with the exception of hormones for hypothyroidism or estrogen replacement therapy (ERT), anti estrogen analogs, agonists required to suppress serum testosterone levels), or any investigational therapy within 14 days prior to the first dose of study drug, or has not recovered to less than a grade 2 adverse effect(s) of the previous therapy.

• Received a biologic (G-CSF, GM-CSF or erythropoietin) within 28 days prior to the first dose of study drug.

• Steroid therapy for anti-neoplastic intent within seven days prior to the first dose of study drug.

• Has consumed grapefruit or grapefruit products within 3 days prior to the first dose of study drug.

• Significant history of cardiovascular disease, renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, or hepatic disease that in the opinion of the investigator would adversely affect his/her participating in this study.

• Positive for HIV

• A history of other active malignancies within the past 3 years prior to screening, with the exception of:

• Adequately treated in situ carcinoma of the cervix uteri

• Basal or squamous cell carcinoma of the skin

• Previous malignancy confined and surgically resected with curative intent

• Evidence of other clinically significant uncontrolled condition(s) including, but not limited to:

• Active systemic fungal infection

• Diagnosis of fever and neutropenia within 1 week prior to study drug administration.

Related Conditions & MeSH terms

• Lung Neoplasms
• Small Cell Lung Cancer
• Small Cell Lung Carcinoma

Intervention

Drug:
• ABT-263
Phase 1 dosing under two different schedules: 14 days on drug, 7 days off or continuous dosing. - 50 patients with SCLC and non-hematologic malignancies. Enrollment is closed in this arm of the study. Phase 2a dosing under two different schedules: 14 days on drug, 7 days off or continuous dosing. - 40 patients with SCLC

Locations

Country	Name	City	State
Canada	Site Reference ID/Investigator# 7493	Edmonton
Canada	Site Reference ID/Investigator# 7635	Ottawa
United Kingdom	Site Reference ID/Investigator# 18541	Leicester
United Kingdom	Site Reference ID/Investigator# 2622	Manchester
United States	Site Reference ID/Investigator# 8324	Atlanta	Georgia
United States	Site Reference ID/Investigator# 3755	Aurora	Colorado
United States	Site Reference ID/Investigator# 2625	Baltimore	Maryland
United States	Site Reference ID/Investigator# 12343	Bethesda	Maryland
United States	Site Reference ID/Investigator# 11941	Boston	Massachusetts
United States	Site Reference ID/Investigator# 2626	Boston	Massachusetts
United States	Site Reference ID/Investigator# 4934	Charlotte	North Carolina
United States	Site Reference ID/Investigator# 2623	Chicago	Illinois
United States	Site Reference ID/Investigator# 11942	Los Angeles	California
United States	Site Reference ID/Investigator# 2624	Nashville	Tennessee
United States	Site Reference ID/Investigator# 13605	Peoria	Arizona
United States	Site Reference ID/Investigator# 5261	Phoenix	Arizona
United States	Site Reference ID/Investigator# 4718	Sacramento	California
United States	Site Reference ID/Investigator# 6650	Tacoma	Washington

Sponsors (2)

Lead Sponsor	Collaborator
AbbVie (prior sponsor, Abbott)	Genentech, Inc.

Countries where clinical trial is conducted

United States,  Canada,  United Kingdom, 

References & Publications (1)

Gandhi L, Camidge DR, Ribeiro de Oliveira M, Bonomi P, Gandara D, Khaira D, Hann CL, McKeegan EM, Litvinovich E, Hemken PM, Dive C, Enschede SH, Nolan C, Chiu YL, Busman T, Xiong H, Krivoshik AP, Humerickhouse R, Shapiro GI, Rudin CM. Phase I study of Nav — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety assessment		Repeating sequence of 14 days on therapy and 7 days off or continuous dosing
Primary	Dose limiting toxicity determination		Repeating sequence of 14 days on therapy and 7 days off or continuous dosing
Primary	Maximum tolerated dose determination		Repeating sequence of 14 days on therapy and 7 days off or continuous dosing
Primary	Pharmacokinetic profile evaluation		Repeating sequence of 14 days on therapy and 7 days off or continuous dosing
Secondary	Extended safety assessment at the recommended Phase 2 dose		Repeating sequence of 14 days on therapy and 7 days off or continuous dosing
Secondary	Preliminary efficacy assessment		Repeating sequence of 14 days on therapy and 7 days off or continuous dosing