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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Monotherapy, once daily | Experimental |
| |
| Combination with carboplatin | Experimental |
| |
| Combination with docetaxel | Experimental |
| |
| Monotherapy, twice daily | Experimental |
| |
| IV Monotherapy, once daily | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ABT-348 | Drug | An oral dose of ABT-348, once daily on Day 1, Day 8, and Day 15 of each 28 day cycle. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 | At each treatment visit | |
| Study the pharmacokinetic of ABT-348 | At study visits | |
| Dose limiting toxicity determination | At each treatment visit until dose-limiting toxicities observed |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | At RPTD treatment visit | |
| 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. |
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Inclusion Criteria:
Histological confirmation of locally advanced or metastatic solid tumor.
Eastern Cooperative Oncology Group Status of 0-2
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
Adequate liver function as demonstrated by serum bilirubin < 2 x ULN and AST and ALT ≤ 2.5 x ULN
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)
QTc interval < 500 msec
Left Ventricular Ejection Fraction > 50%
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.
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:
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)
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| Name | Affiliation | Role |
|---|---|---|
| Gary Gordon, MD | AbbVie | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Site Reference ID/Investigator# 26525 | Chicago | Illinois | 60637 | United States | ||
| Site Reference ID/Investigator# 26524 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29551775 | Derived | 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. |
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| ID | Term |
|---|---|
| C577638 | ilorasertib |
| D016190 | Carboplatin |
| D000077143 | Docetaxel |
| ID | Term |
|---|---|
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
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| ABT-348 and carboplatin | Drug | 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. |
|
| ABT-348 and docetaxel | Drug | 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. |
|
| ABT-348 | Drug | An oral dose of ABT-348, twice daily on Day 1, Day 8, and Day 15 of each 28 day cycle |
|
| ABT-348 | Drug | An IV administration of ABT-348 two hour infusion on Day 1, Day 8 and Day 15 of each 28 day cycle. |
|
| At each treatment visit |
| Houston |
| Texas |
| 77030 |
| United States |
| D003516 |
| Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D004224 | Diterpenes |
| D013729 | Terpenes |