Assess the Oral Bioavailability of a New ABT-263 Formulation in Subjects With Cancer

NCT00982566 | Completed Phase 1

• 1 other identifier: M11-069
• Study Type: interventional
• Target: 37
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a randomized, single dose, open-label, multicenter crossover study to determine the oral bioavailability of a new ABT-263 formulation relative to that of the current ABT-263 formulation being administered in ongoing Phase 1/2a studies. Approximately 48 evaluable subjects with lymphoid malignancies, including chronic lymphocytic leukemia, and solid tumors will be enrolled in this study.

Conditions

Lymphoid Malignancy; Solid Tumors

Outcome Measures

Primary Outcomes (1)

• Assessment of Oral Bioavailability

  Assess the oral bioavailability of Formulation B1, Formulation B2, Formulation C, and Formulation D relative to that of Formulation A being assessed in ongoing Phase 1/2a ABT-263 studies

  Two Period and Three Period crossover design

Secondary Outcomes (1)

• Adverse Events Tabulation

  Two Period and Three Period crossover design

Study Arms (16)

Sequence I

EXPERIMENTAL

Drug: ABT-263

Sequence II

EXPERIMENTAL

Drug: ABT-263

Sequence III

EXPERIMENTAL

Drug: ABT-263

Sequence IV

EXPERIMENTAL

Drug: ABT-263

Sequence V

EXPERIMENTAL

Drug: ABT-263

Sequence VI

EXPERIMENTAL

Drug: ABT-263

Sequence VII

EXPERIMENTAL

Drug: ABT-263

Sequence VIII

EXPERIMENTAL

Drug: ABT-263

Sequence IX

EXPERIMENTAL

Drug: ABT-263

Sequence X

EXPERIMENTAL

Drug: ABT-263

Sequence XI

EXPERIMENTAL

Drug: ABT-263

Sequence XII

EXPERIMENTAL

Drug: ABT-263

Sequence XIII

EXPERIMENTAL

Drug: ABT-263

Sequence XIV

EXPERIMENTAL

Drug: ABT-263

Sequence XVI

EXPERIMENTAL

Drug: ABT-263

Sequence XV

EXPERIMENTAL

Drug: ABT-263

Interventions

ABT-263 DRUG

Part 1: Single (oral) dose of 250 mg of Formulation B1 vs. single (oral) dose of 250 mg of Formulation A

Sequence I; Sequence II

Eligibility Criteria

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

You may qualify if:

• Subject must be \>= 18 years of age.
• Subject has a lymphoid malignancy (histologic or cytologic confirmation), or solid tumor (radiographic, histologic, or cytologic confirmation) that is either:
• relapsed or refractory to standard therapy, or
• no known effective therapy exists.
• In the investigator's opinion, the subject's life expectancy is at least 90 days.
• Subjects with known brain metastases must have clinically controlled neurologic symptoms, defined as surgical excision and/or radiation therapy followed by 21 days of stable neurologic function and no evidence of CNS disease progression as determined by CT or MRI within 21 days prior to the first dose of study drug.
• If clinically indicated, subjects must have documented brain imaging (MRI or CT) negative for subdural or epidural hematoma within 28 days prior to the first dose of study drug.
• Subject has an Eastern Cooperative Oncology Group (ECOG) performance score of \<= 2.
• Subject must have adequate bone marrow, renal and hepatic function per local laboratory reference range as follows:
• Bone marrow: Absolute Neutrophil count (ANC) \>= 1,000/µL; Platelets \>= 100,000/mm3 (independent of platelet transfusions within 3 months prior to starting study drug); Hemoglobin \>= 9.0 g/dL;
• Renal function: serum creatinine \<= 2.0 mg/dL or calculated creatinine clearance \>= 50 mL/min;
• Hepatic function and enzymes: AST and ALT \<= 2.5 x the upper normal limit (ULN) of institution's normal range; Bilirubin \<= 1.5 x ULN. Subjects with Gilbert's Syndrome may have a Bilirubin \> 1.5 x ULN; Subjects with liver metastasis may have an AST and ALT of \<= 5.0 x ULN;
• Coagulation: aPTT, PT not to exceed 1.2 x ULN.
• Female subjects must be surgically sterile, postmenopausal (for at least one year), or have negative results for a pregnancy test performed as follows:
• At Screening on a serum sample obtained within 14 days prior to initial study drug administration, and

You may not qualify if:

• Subject has undergone an allogeneic stem cell transplant.
• Subject has an underlying condition predisposing them to bleeding or currently exhibits signs of clinically significant bleeding.
• Subject has a recent history of non-chemotherapy induced thrombocytopenic associated bleeding within one year prior to the first dose of study drug.
• Subject has active peptic ulcer disease or other hemorrhagic esophagitis/gastritis.
• Female subject is pregnant or breast-feeding.
• Subject has a history of or an active medical condition(s) that affects absorption or motility (e.g., Crohn's disease, celiac disease, gastroparesis, short bowel syndrome, etc.).
• Subject has tested positive for HIV (due to potential drug-drug interactions between anti retroviral inhibitors and ABT-263, as well as anticipated ABT-263 mechanism based lymphopenia that may potentially increase the risk of opportunistic infections and potential drug-drug interactions with certain anti infective agents).
• Subject exhibits evidence of other clinically significant uncontrolled condition(s) including, but not limited to:
• active systemic fungal infection;
• diagnosis of fever and neutropenia within one week prior to study drug administration.
• Subject has received any of the following anti-cancer therapies 14 days prior to the first dose of study drug, or has not recovered to less than grade 2 clinically significant adverse effect(s)/toxicity(s) of the previous therapies:
• chemotherapy, immunotherapy, radiotherapy;
• hormonal therapy (with the exception of hormones for hypothyroidism or estrogen replacement therapy \[ERT\], or agonists required to suppress serum testosterone levels \[e.g., LHRH, GnRH, etc.\] for subjects with prostate cancer if on a stable dose for 21 days prior to the first dose of study drug);
• any investigational therapy, including targeted small molecule agents
• Subject has received a biologic agent for anti-neoplastic intent within 30 days prior to the first dose of study drug.

Sponsors & Collaborators

• AbbVie: lead
• Genentech, Inc.: collaborator

Related Publications (1)

• Xiong H, Pradhan RS, Nada A, Krivoshik AP, Holen KD, Rhodes JW, Gordon GB, Humerickhouse R, Awni WM. Studying navitoclax, a targeted anticancer drug, in healthy volunteers--ethical considerations and risk/benefit assessments and management. Anticancer Res. 2014 Jul;34(7):3739-46.

  PMID: 24982396 RESULT

MeSH Terms

Interventions

navitoclax

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: September 22, 2009
• First Posted: September 23, 2009
• Study Start: October 1, 2009
• Primary Completion: October 1, 2010
• Study Completion: December 1, 2010
• Last Updated: November 21, 2017

Record last verified: 2011-01