A Study of the Safety and Pharmacokinetics of RO6839921, An MDM2 Antagonist, in Patients With Advanced Cancers, Including Acute Myeloid Leukemia.
This open label, Phase I study of RO6839921 is a dose-escalation study with two arms. Prior to investigations in either arm, patients in a single cohort, Cohort 0, will receive non-escalating, intravenous (IV) doses of RO6839921 daily on Days 1-5 of a 28-day cycle. Interim PK and safety data from this cohort will be evaluated before initiating dose-escalation.
In arm A, RO6839921 will be given to patients with advanced solid tumor malignancies. In Arm B, RO6839921 will be given to patients with relapsed/refractory acute myeloid leukemia (AML). The arms will escalate independently. Escalation will begin in solid tumor patients (Arm A) in single patient cohorts, using a new Continual Reassessment Method (n-CRM). Escalation for AML patients will be initiated at or below the dose level that causes >/= Grade 2 hematologic side effects in Arm A. Escalation in AML patients will follow a rolling 6 design.
In both arms, RO6839921 will be administered by IV infusion on Days 1-5 of 28-day cycles.
There will be no intrapatient dose escalation. All patients may be treated until disease progression/relapse or unacceptable toxicity.
|Study Design:||Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||A Multi-Center, Open-Label, First-in-Human, Phase I Dose-Escalation Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO6839921, An MDM2 Antagonist, Following Intravenous Administration in Patients With Advanced Malignancies, Including Acute Myeloid Leukemia (AML)|
- Incidence of adverse events [ Time Frame: Approximately 1 year ]
- Incidence of dose-limiting toxicities [ Time Frame: Approximately 1 year ]
- Plasma area under the concentration-time curve (AUC) of RO6839921. [ Time Frame: Up to Day 22 ]
- Changes in serum macrophage inhibitory cytokine-1 (MIC-1) expression measured by enzyme-linked immunosorbent assay (ELISA) [ Time Frame: Up to Day 22 ]
|Actual Study Start Date:||April 21, 2014|
|Estimated Study Completion Date:||May 16, 2018|
|Estimated Primary Completion Date:||May 16, 2018 (Final data collection date for primary outcome measure)|
|Experimental: Acute myeloid leukemia patients||
Escalating IV doses of RO6839921 in AML patients. Escalation will follow an adapted rolling 6 design. Starting dose </= dose inducing Grade 2 toxicity in patients with solid tumors. RO6839921 will be given on Days 1-5 of 28-day cycles. Treatment will continue until disease progression, unacceptable toxicity or study discontinuation.
|Experimental: Cohort 0||
Non-escalating IV doses given on Days 1-5 of Cycle 1.
|Experimental: Solid tumor patients||
Escalating IV doses of RO6839921 in solid tumor patients. Dose escalation will be calculated using the new Continual Reassessment Method (nCRM). RO6839921 will be given on Days 1-5 of 28-day cycles. Treatment will continue until disease progression, unacceptable toxicity or study discontinuation.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02098967
|United States, Colorado|
|University of Colorado|
|Aurora, Colorado, United States, 80045|
|United States, Missouri|
|Saint Louis, Missouri, United States, 63110|
|United States, South Carolina|
|Medical University of South Carolina; Hollings Cancer Center|
|Charleston, South Carolina, United States, 29425|
|University Health Network; Princess Margaret Hospital; Medical Oncology Dept|
|Toronto, Ontario, Canada, M5G 2M9|
|Jewish General Hospital / McGill University|
|Montreal, Quebec, Canada, H3T 1E2|
|Study Director:||Clinical Trials||Hoffmann-La Roche|