ABT-348 as Monotherapy or Combination With Carboplatin or Docetaxel to Treat Advanced Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier:
NCT01110486
First received: March 26, 2010
Last updated: November 4, 2013
Last verified: November 2013
  Purpose

The purpose of this study is to determine the safety, pharmacokinetics and maximum tolerated dose of ABT-348 as monotherapy and when given in combination with carboplatin or docetaxel.


Condition Intervention Phase
Advanced Solid Tumors
Drug: ABT-348
Drug: ABT-348 and carboplatin
Drug: ABT-348 and docetaxel
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Study Evaluating the Safety and Pharmacokinetics of ABT-348 as Monotherapy, in Combination With Carboplatin or in Combination With Docetaxel in Subjects With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by AbbVie:

Primary Outcome Measures:
  • Determine the safety profile (Adverse events by toxicity grade and relationship to study drug, serious adverse events, adverse events leading to discontinuation and relevant clinical laboratory abnormalities) of ABT-348 as monotherapy or in combination [ Time Frame: At each treatment visit ] [ Designated as safety issue: Yes ]
  • Study the pharmacokinetic of ABT-348 [ Time Frame: At study visits ] [ Designated as safety issue: No ]
  • Dose limiting toxicity determination [ Time Frame: At each treatment visit until dose-limiting toxicities observed ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Evaluate safety at the recommended Phase 2 dose (RPTD) and schedule of ABT-348 as monotherapy, when in combination with carboplatin or in combination with docetaxel. [ Time Frame: At RPTD treatment visit ] [ Designated as safety issue: Yes ]
  • Evaluate preliminary efficacy data regarding objective response rate (ORR), time to progression (TTP), duration of overall response, and ECOG performance status of ABT-348 as monotherapy, when in combination with carboplatin or docetaxel. [ Time Frame: At each treatment visit ] [ Designated as safety issue: No ]

Enrollment: 102
Study Start Date: March 2010
Study Completion Date: September 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Monotherapy, once daily Drug: ABT-348
An oral dose of ABT-348, once daily on Day 1, Day 8, and Day 15 of each 28 day cycle.
Experimental: Combination with carboplatin Drug: ABT-348 and carboplatin
An oral dose of ABT-348 will begin in Cycle 2on Day 1 and Day 8; and an IV dose of carboplatin (AUC 5.0) on Day 1 of each 21-day cycle.
Experimental: Combination with docetaxel Drug: ABT-348 and docetaxel
ABT-348 dosing will begin in Cycle 2. An oral dose of ABT-348 on Day 1 and Day 8; and an IV dose of docetaxel (75 mg/m2) on Day 1 of each 21-day cycle.
Experimental: Monotherapy, twice daily Drug: ABT-348
An oral dose of ABT-348, twice daily on Day 1, Day 8, and Day 15 of each 28 day cycle
Experimental: IV Monotherapy, once daily Drug: ABT-348
An IV administration of ABT-348 two hour infusion on Day 1, Day 8 and Day 15 of each 28 day cycle.

Detailed Description:

The primary purpose of this study is to determine the safety, pharmacokinetics and maximum tolerated dose of ABT-348 as monotherapy and when given in combination with carboplatin or docetaxel. The secondary purpose of this study is to evaluate safety at the recommended Phase 2 dose and evaluate preliminary efficacy data regarding objective response rate time to progression, duration of overall response, and ECOG performance status of ABT-348 as monotherapy and when given in combination with carboplatin or docetaxel.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histological confirmation of locally advanced or metastatic solid tumor.

    • That is either refractory after standard of care therapy for the disease for which standard of care therapy is not reliably effective or does not exists, or
    • For which carboplatin has been determined to be an appropriate therapy, per the investigator, or
    • For which docetaxel has been determined to be an appropriate therapy, per the investigator.
  2. Eastern Cooperative Oncology Group Status of 0-2
  3. Serum creatinine value of ≤ 1.5 times the upper limit of normal (ULN) and either an estimated creatinine clearance value as determined by the Cockcroft-Gault formula or based on a 24 hour urine collection creatinine clearance value of ≥ 50 mL/min
  4. Adequate liver function as demonstrated by serum bilirubin < 2 x ULN and AST and ALT ≤ 2.5 x ULN
  5. Adequate bone marrow as demonstrated by absolute neutrophil count (ANC) ≥ 1,500/mm2 (1.5 x 109/L); Platelets ≥ 100,000/mm2 (100 x 109/L); Hemoglobin ≥ 9.0 g/dL (1.4 mmol/L)
  6. QTc interval < 500 msec
  7. Left Ventricular Ejection Fraction > 50%
  8. Women of child-bearing potential and men must agree to use adequate contraception (one of the following listed below) prior to the study entry, for the duration of study participation and up to 3 months following completion of therapy.
  9. Capable of understanding and complying with parameters as outlined in the protocol and able to sign informed consent, approved by an Institutional Review Board (IRB) prior to the initiation of any screening or study-specific procedures.

Exclusion Criteria:

  1. Subject has known active CNS involvement. The subject has untreated brain or meningeal metastases.
  2. Subject has received anti-cancer therapy within a period of 21 days or 5 half lives (whichever is shorter) prior to Study Day 1
  3. Subject has unresolved toxicities from prior anti-cancer therapy, grade 2 or higher clinically significant toxicity (excluding alopecia)
  4. Subject has had major surgery within 28 days prior to Study Day 1
  5. Subject currently exhibits symptomatic or persistent, uncontrolled hypertension defined as diastolic blood pressure > 90 mmHg or systolic blood pressure > 140 mmHg
  6. Subject has proteinuria grade > 1 7. Subject is receiving therapeutic anticoagulation therapy. Low dose anti coagulation (e.g., low dose heparin or warfarin) for catheter prophylaxis will be permitted.

8. Clinically significant uncontrolled condition(s) 9.Psychiatric illness/social situation that would limit compliance with study requirements 10. Subject has a known infection with HIV, Hepatitis B or Hepatitis C 11. Subject with poorly controlled diabetes mellitus 12. Subject enrolled in Arm A, B, C and D is unable to swallow or absorb oral tablets normally 13. Any medical condition which in the opinion of the study investigator places the subject at an unacceptably high risk for toxicities 14. Female subjects who are lactating or pregnant 15. Subject enrolled in Arm E has hypersensitivity to drugs formulated with polyethoxylated castor oli (Cremophor)

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01110486

Locations
United States, Illinois
Site Reference ID/Investigator# 26525
Chicago, Illinois, United States, 60637
United States, Texas
Site Reference ID/Investigator# 26524
Houston, Texas, United States, 77030
Sponsors and Collaborators
AbbVie (prior sponsor, Abbott)
Investigators
Study Director: Gary Gordon, MD AbbVie
  More Information

No publications provided

Responsible Party: AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier: NCT01110486     History of Changes
Other Study ID Numbers: M10-944
Study First Received: March 26, 2010
Last Updated: November 4, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Docetaxel
Carboplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014