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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT02098967
First received: March 25, 2014
Last updated: November 1, 2016
Last verified: November 2016
  Purpose

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.


Condition Intervention Phase
Neoplasms, Myelogenous Leukemia, Acute Drug: RO6839921 Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
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)

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Incidence of adverse events [ Time Frame: Approximately 1 year ]
  • Incidence of dose-limiting toxicities [ Time Frame: Approximately 1 year ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 68
Study Start Date: April 2014
Estimated Study Completion Date: May 2017
Estimated Primary Completion Date: May 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Acute myeloid leukemia patients Drug: RO6839921
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 Drug: RO6839921
Non-escalating IV doses given on Days 1-5 of Cycle 1.
Experimental: Solid tumor patients 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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02098967

Locations
United States, Colorado
Aurora, Colorado, United States, 80045
United States, Missouri
Saint Louis, Missouri, United States, 63110
United States, South Carolina
Charleston, South Carolina, United States, 29425
Canada, Ontario
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Montreal, Quebec, Canada, H3T 1E2
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02098967     History of Changes
Other Study ID Numbers: NP28903
RG7775 ( Other Identifier: Roche )
Study First Received: March 25, 2014
Last Updated: November 1, 2016

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms

ClinicalTrials.gov processed this record on June 22, 2017