A Study of the Safety and Pharmacokinetics of RO6839921, An MDM2 Antagonist, in Patients With Advanced Cancers, Including Acute Myeloid Leukemia.

May 16, 2018 updated by: Hoffmann-La Roche

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)

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 Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

68

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • University Health Network; Princess Margaret Hospital; Medical Oncology Dept
    • Quebec
      • Montreal, Quebec, Canada, H3T 1E2
        • Jewish General Hospital / McGill University
  • United States
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina; Hollings Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Cohort 0 and Arm A

  • Patient must have histologically or cytologically confirmed advanced cancer for which standard cures or relieving measures either do not exist, are ineffective or are not acceptable to the patient.
  • Measureable disease according to RECIST criteria version 1.1.
  • ECOG performance status of 0 to 1.
  • Adequate bone marrow function.

Arm B

  • Patients with documented acute myeloid leukemia (AML), except for acute promyelocytic leukemia.
  • Patients with relapsed/refractory AML or patients who have not received prior therapy who are high risk according to European LeukemiaNet (ELN) criteria.
  • ECOG performance status of 0 to 2.

For Cohort 0, Arms A and B

  • Life expectancy of >/= 12 weeks.
  • Age >/= 18 years or older.
  • All patients must be willing to use effective methods of contraception until 10 days after the last dose; women must not be pregnant or breast-feeding.
  • Adequate renal and hepatic function.
  • Patients with stable central nervous system (CNS) tumors are eligible.
  • There are no requirements or limitations on the amount or type of prior anti-tumor/anti-leukemia therapy.

Exclusion Criteria:

Cohort 0 and Arm A

  • Patients with a history of any form of leukemia except for Stage 0 and 1 chronic lymphocytic leukemia (CLL) not requiring treatment.
  • Patients receiving any cancer treatment within 21 days of start of study medication. Patients must also have recovered from severe side effects due to prior treatment before study start.
  • Patients with known bone marrow disorders that may interfere with bone marrow recovery, or patients with delayed recovery from prior chemoradiotherapy.
  • Patients with known bleeding or clotting disorders or non-drug-induced low platelet count.

Arm B

- Patients receiving any cancer treatment within 14 days of start of study medication. Hydroxyurea may be taken until first administration of the study drug. Patients must also have recovered from severe side effects due to prior treatment before study start.

For Cohort 0, Arms A and B

  • Patients receiving any other test drugs within 30 days of start of study medication
  • Patients receiving the cytochrome P450 inhibitors, substrates or inducers specified in the protocol.
  • Anticoagulation or antiplatelet treatment must be discontinued 7 days prior to start of study medication.
  • Patients who have received hormonal therapy (except for prostate cancer treatment and hormone replacement therapy) within the 2 weeks prior to start of study medication.
  • Patients with evidence of electrolyte imbalance, which may be treated to meet eligibility.
  • Serum albumin < 2.8 g/dL.
  • HIV-positive patients who are currently receiving combination antiretroviral therapy.
  • Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 0
Drug: RO6839921
Non-escalating IV doses given on Days 1-5 of Cycle 1.
Drug: RO6839921
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.
Drug: RO6839921
Escalating IV doses of RO6839921 in AML patients. Escalation will follow an adapted rolling 6 design. Starting dose
Experimental: Acute myeloid leukemia patients
Drug: RO6839921
Non-escalating IV doses given on Days 1-5 of Cycle 1.
Drug: RO6839921
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.
Drug: RO6839921
Escalating IV doses of RO6839921 in AML patients. Escalation will follow an adapted rolling 6 design. Starting dose
Experimental: Solid tumor patients
Drug: RO6839921
Non-escalating IV doses given on Days 1-5 of Cycle 1.
Drug: RO6839921
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.
Drug: RO6839921
Escalating IV doses of RO6839921 in AML patients. Escalation will follow an adapted rolling 6 design. Starting dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence of adverse events
Time Frame: Approximately 1 year
Approximately 1 year
Incidence of dose-limiting toxicities
Time Frame: Approximately 1 year
Approximately 1 year

Secondary Outcome Measures

Outcome Measure
Time Frame
Plasma area under the concentration-time curve (AUC) of RO6839921.
Time Frame: Up to Day 22
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
Up to Day 22

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hoffmann-La Roche

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 21, 2014

Primary Completion (Actual)

May 7, 2018

Study Completion (Actual)

May 7, 2018

Study Registration Dates

First Submitted

March 25, 2014

First Submitted That Met QC Criteria

March 25, 2014

First Posted (Estimate)

March 28, 2014

Study Record Updates

Last Update Posted (Actual)

May 17, 2018

Last Update Submitted That Met QC Criteria

May 16, 2018

Last Verified

May 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NP28903
  • RG7775 (Other Identifier: Roche)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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