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

NCT00445198 | Completed Phase 1

• 2 other identifiers: M06-8222006-003298-28
• Study Type: interventional
• Target: 86
• Locations: 3 countries
• Sites: 18

Brief 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.

Conditions

Small Cell Lung Cancer; Small Cell Lung Carcinoma

Keywords

SCLC

Outcome Measures

Primary Outcomes (4)

• Safety assessment

  Repeating sequence of 14 days on therapy and 7 days off or continuous dosing

• Dose limiting toxicity determination

  Repeating sequence of 14 days on therapy and 7 days off or continuous dosing

• Maximum tolerated dose determination

  Repeating sequence of 14 days on therapy and 7 days off or continuous dosing

• Pharmacokinetic profile evaluation

  Repeating sequence of 14 days on therapy and 7 days off or continuous dosing

Secondary Outcomes (2)

• Extended safety assessment at the recommended Phase 2 dose

  Repeating sequence of 14 days on therapy and 7 days off or continuous dosing

• Preliminary efficacy assessment

  Repeating sequence of 14 days on therapy and 7 days off or continuous dosing

Study Arms (1)

Phase 1 and Phase 2a

EXPERIMENTAL

Drug: ABT-263

Interventions

ABT-263 DRUG

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

Phase 1 and Phase 2a

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AbbVie (prior sponsor, Abbott): lead
• Genentech, Inc.: collaborator

Study Sites (18)

Site Reference ID/Investigator# 13605

Peoria, Arizona, 85381, United States

Location

Site Reference ID/Investigator# 5261

Phoenix, Arizona, 85013, United States

Location

Site Reference ID/Investigator# 11942

Los Angeles, California, 90095-7187, United States

Location

Site Reference ID/Investigator# 4718

Sacramento, California, 95817, United States

Location

Site Reference ID/Investigator# 3755

Aurora, Colorado, 80045-0510, United States

Location

Site Reference ID/Investigator# 8324

Atlanta, Georgia, 30322, United States

Location

Site Reference ID/Investigator# 2623

Chicago, Illinois, 60612, United States

Location

Site Reference ID/Investigator# 2625

Baltimore, Maryland, 21231-1000, United States

Location

Site Reference ID/Investigator# 12343

Bethesda, Maryland, 20892, United States

Location

Site Reference ID/Investigator# 11941

Boston, Massachusetts, 02215, United States

Location

Site Reference ID/Investigator# 2626

Boston, Massachusetts, 02215, United States

Location

Site Reference ID/Investigator# 4934

Charlotte, North Carolina, 28204, United States

Location

Site Reference ID/Investigator# 2624

Nashville, Tennessee, 37203, United States

Location

Site Reference ID/Investigator# 6650

Tacoma, Washington, 98405, United States

Location

Site Reference ID/Investigator# 7493

Edmonton, T6G 1Z2, Canada

Location

Site Reference ID/Investigator# 7635

Ottawa, K1H 8L6, Canada

Location

Site Reference ID/Investigator# 18541

Leicester, LE1 5WW, United Kingdom

Location

Site Reference ID/Investigator# 2622

Manchester, M20 4BX, United Kingdom

Location

Related 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 Navitoclax (ABT-263), a novel Bcl-2 family inhibitor, in patients with small-cell lung cancer and other solid tumors. J Clin Oncol. 2011 Mar 1;29(7):909-16. doi: 10.1200/JCO.2010.31.6208. Epub 2011 Jan 31.

  PMID: 21282543 RESULT

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

navitoclax

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2007
• First Posted: March 8, 2007
• Study Start: April 1, 2007
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: June 6, 2018

Record last verified: 2013-01

Locations

CA (2); US (14); GB (2)