Clinical trial NCT01110486: ABT-348 as Monotherapy or Combination With Carboplatin or Docetaxel to Treat Advanced Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2010-04-26
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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)

Primary outcomes:
measure: 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
timeFrame: At each treatment visit
measure: Study the pharmacokinetic of ABT-348
timeFrame: At study visits
measure: Dose limiting toxicity determination
timeFrame: At each treatment visit until dose-limiting toxicities observed
Secondary outcomes:
measure: 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.
timeFrame: At RPTD treatment visit
measure: 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.
timeFrame: At each treatment visit
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Site Reference ID/Investigator# 26525
state: Illinois
city: Houston
country: United States
facility: Site Reference ID/Investigator# 26524
state: Texas
Study officials:
affiliation: AbbVie
name: Gary Gordon, MD
role: STUDY_DIRECTOR
References:
citation: Maitland ML, Piha-Paul S, Falchook G, Kurzrock R, Nguyen L, Janisch L, Karovic S, McKee M, Hoening E, Wong S, Munasinghe W, Palma J, Donawho C, Lian GK, Ansell P, Ratain MJ, Hong D. Clinical pharmacodynamic/exposure characterisation of the multikinase inhibitor ilorasertib (ABT-348) in a phase 1 dose-escalation trial. Br J Cancer. 2018 Apr;118(8):1042-1050. doi: 10.1038/s41416-018-0020-2. Epub 2018 Mar 19.