Clinical trial NCT01292655: Study to Evaluate the Safety and Tolerability of IV Doses of BMS-906024 in Subjects With Advanced or Metastatic Solid Tumors
Official title: Phase 1 Ascending Multiple-Dose Study to Evaluate the Safety, Pharmacokinetics (PK) and Pharmacodynamics (PD) of BMS-906024 in Subjects With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2011-02-09
Enrollment: 94
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 identify a safe and tolerable dose of BMS-906024 in subjects with advanced or metastatic solid tumors who no longer respond to or have relapsed from standard therapies.


Eligibility criteria: For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.

Inclusion Criteria:

* Subjects with advanced or metastatic solid tumors (non-hematologic refractory to or relapsed from standard therapies or for which there is no known effective treatment during dose escalation
* Subjects with squamous non-small cell lung cancer and triple-negative breast cancer or other solid tumor types for which Notch activation has been demonstrated (such as pancreatic, ovarian and melanoma) during dose expansion
* Biopsy accessible tumor (may be waived under certain circumstances)
* Life expectancy of at least 3 months
* Eastern Cooperative Oncology Group (ECOG) 0-1
* Adequate organ and bone marrow function

Exclusion Criteria:

* Infection
* Elevated triglycerides
* Gastrointestinal (GI) disease with increased risk of diarrhea \[e.g. inflammatory bowel disease (IBD)\]
* Taking medications known to increase risk of Torsades De Pointes

Primary outcomes:
measure: Number of subjects with adverse events as a measure of safety and tolerability
timeFrame: Weekly assessments until study discontinuation due to disease progression or unacceptable adverse event as well as an assessment 30 day after treatment discontinuation with an average time on study expected to be <1 year
Secondary outcomes:
measure: Tumor assessments using response evaluation criteria in solid tumors (RECIST) v1.1
timeFrame: Tumor assessments at least every 8 weeks during treatment period
measure: PD changes from baseline in the expression of Notch pathway-related genes in surrogate tissues (peripheral blood cells) and tumor biopsies
timeFrame: PD changes from baseline during the first 4-5 weeks of dosing
measure: PK parameters for BMS-906024 and its metabolite BMS-911557, maximum observed concentration (Cmax)
timeFrame: PK at multiple time points during the first 8 weeks of dosing
measure: PK parameters for BMS-906024 and its metabolite BMS-911557, minimum observed concentration (Cmin)
timeFrame: PK at multiple time points during the first 8 weeks of dosing
measure: PK parameters for BMS-906024 and its metabolite BMS-911557, time to reach maximum observed concentration (Tmax)
timeFrame: PK at multiple time points during the first 8 weeks of dosing
measure: PK parameters for BMS-906024 and its metabolite BMS-911557, terminal phase elimination half-life (T-Half)
timeFrame: PK at multiple time points during the first 8 weeks of dosing
measure: PK parameters for BMS-906024 and its metabolite BMS-911557, accumulation index (AI)
timeFrame: PK at multiple time points during the first 8 weeks of dosing
measure: PK parameters for BMS-906024 and its metabolite BMS-911557, area under the concentration-time curve (AUC)
timeFrame: PK at multiple time points during the first 8 weeks of dosing
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Anthony El-Khoueiry, Md
state: California
city: Atlanta
country: United States
facility: Winship Cancer Institute.
state: Georgia
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Jackson
country: United States
facility: University Of Mississippi Medical Center
state: Mississippi
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Houston
country: United States
facility: The Methodist Hospital Research Institute
state: Texas
city: Parkville
country: Australia
facility: Local Institution
state: Victoria
city: Toronto
country: Canada
facility: Local Institution
state: Ontario
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Chan D, Kaplan J, Gordon G, Desai J. Activity of the Gamma Secretase Inhibitor AL101 in Desmoid Tumors: A Case Report of 2 Adult Cases. Curr Oncol. 2021 Sep 21;28(5):3659-3667. doi: 10.3390/curroncol28050312.