Ignite Creation Date:
2025-12-25 @ 12:34 AM
Ignite Modification Date:
2026-02-12 @ 6:41 AM
Study NCT ID:
NCT02098967
Status:
COMPLETED
Last Update Posted:
2018-05-17
First Post:
2014-03-25
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
A Study of the Safety and Pharmacokinetics of RO6839921, An MDM2 Antagonist, in Patients With Advanced Cancers, Including Acute Myeloid Leukemia.
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D007951', 'term': 'Leukemia, Myeloid'}], 'ancestors': [{'id': 'D007938', 'term': 'Leukemia'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D006402', 'term': 'Hematologic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C000719090', 'term': 'RO6839921'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 68}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2014-04-21', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2018-05', 'completionDateStruct': {'date': '2018-05-07', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2018-05-16', 'studyFirstSubmitDate': '2014-03-25', 'studyFirstSubmitQcDate': '2014-03-25', 'lastUpdatePostDateStruct': {'date': '2018-05-17', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2014-03-28', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2018-05-07', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Incidence of adverse events', 'timeFrame': 'Approximately 1 year'}, {'measure': 'Incidence of dose-limiting toxicities', 'timeFrame': 'Approximately 1 year'}], 'secondaryOutcomes': [{'measure': 'Plasma area under the concentration-time curve (AUC) of RO6839921.', 'timeFrame': 'Up to Day 22'}, {'measure': 'Changes in serum macrophage inhibitory cytokine-1 (MIC-1) expression measured by enzyme-linked immunosorbent assay (ELISA)', 'timeFrame': 'Up to Day 22'}]}, 'conditionsModule': {'conditions': ['Neoplasms, Myelogenous Leukemia, Acute']}, 'referencesModule': {'references': [{'pmid': '32020437', 'type': 'DERIVED', 'citation': 'Uy GL, Assouline S, Young AM, Blotner S, Higgins B, Chen LC, Yee K. Phase 1 study of the MDM2 antagonist RO6839921 in patients with acute myeloid leukemia. Invest New Drugs. 2020 Oct;38(5):1430-1441. doi: 10.1007/s10637-020-00907-4. Epub 2020 Feb 4.'}, {'pmid': '31734832', 'type': 'DERIVED', 'citation': 'Abdul Razak AR, Miller WH Jr, Uy GL, Blotner S, Young AM, Higgins B, Chen LC, Gore L. A phase 1 study of the MDM2 antagonist RO6839921, a pegylated prodrug of idasanutlin, in patients with advanced solid tumors. Invest New Drugs. 2020 Aug;38(4):1156-1165. doi: 10.1007/s10637-019-00869-2. Epub 2019 Nov 16.'}]}, 'descriptionModule': {'briefSummary': '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.\n\nIn 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.\n\nIn both arms, RO6839921 will be administered by IV infusion on Days 1-5 of 28-day cycles.\n\nThere will be no intrapatient dose escalation. All patients may be treated until disease progression/relapse or unacceptable toxicity.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\nCohort 0 and Arm A\n\n* 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.\n* Measureable disease according to RECIST criteria version 1.1.\n* ECOG performance status of 0 to 1.\n* Adequate bone marrow function.\n\nArm B\n\n* Patients with documented acute myeloid leukemia (AML), except for acute promyelocytic leukemia.\n* Patients with relapsed/refractory AML or patients who have not received prior therapy who are high risk according to European LeukemiaNet (ELN) criteria.\n* ECOG performance status of 0 to 2.\n\nFor Cohort 0, Arms A and B\n\n* Life expectancy of \\>/= 12 weeks.\n* Age \\>/= 18 years or older.\n* 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.\n* Adequate renal and hepatic function.\n* Patients with stable central nervous system (CNS) tumors are eligible.\n* There are no requirements or limitations on the amount or type of prior anti-tumor/anti-leukemia therapy.\n\nExclusion Criteria:\n\nCohort 0 and Arm A\n\n* Patients with a history of any form of leukemia except for Stage 0 and 1 chronic lymphocytic leukemia (CLL) not requiring treatment.\n* 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.\n* Patients with known bone marrow disorders that may interfere with bone marrow recovery, or patients with delayed recovery from prior chemoradiotherapy.\n* Patients with known bleeding or clotting disorders or non-drug-induced low platelet count.\n\nArm B\n\n\\- 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.\n\nFor Cohort 0, Arms A and B\n\n* Patients receiving any other test drugs within 30 days of start of study medication\n* Patients receiving the cytochrome P450 inhibitors, substrates or inducers specified in the protocol.\n* Anticoagulation or antiplatelet treatment must be discontinued 7 days prior to start of study medication.\n* 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.\n* Patients with evidence of electrolyte imbalance, which may be treated to meet eligibility.\n* Serum albumin \\< 2.8 g/dL.\n* HIV-positive patients who are currently receiving combination antiretroviral therapy.\n* Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study.'}, 'identificationModule': {'nctId': 'NCT02098967', 'briefTitle': 'A Study of the Safety and Pharmacokinetics of RO6839921, An MDM2 Antagonist, in Patients With Advanced Cancers, Including Acute Myeloid Leukemia.', 'organization': {'class': 'INDUSTRY', 'fullName': 'Hoffmann-La Roche'}, 'officialTitle': '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)', 'orgStudyIdInfo': {'id': 'NP28903'}, 'secondaryIdInfos': [{'id': 'RG7775', 'type': 'OTHER', 'domain': 'Roche'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Acute myeloid leukemia patients', 'interventionNames': ['Drug: RO6839921']}, {'type': 'EXPERIMENTAL', 'label': 'Cohort 0', 'interventionNames': ['Drug: RO6839921']}, {'type': 'EXPERIMENTAL', 'label': 'Solid tumor patients', 'interventionNames': ['Drug: RO6839921']}], 'interventions': [{'name': 'RO6839921', 'type': 'DRUG', 'description': 'Non-escalating IV doses given on Days 1-5 of Cycle 1.', 'armGroupLabels': ['Cohort 0']}, {'name': 'RO6839921', 'type': 'DRUG', 'description': '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.', 'armGroupLabels': ['Solid tumor patients']}, {'name': 'RO6839921', 'type': 'DRUG', 'description': '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.', 'armGroupLabels': ['Acute myeloid leukemia patients']}]}, 'contactsLocationsModule': {'locations': [{'zip': '80045', 'city': 'Aurora', 'state': 'Colorado', 'country': 'United States', 'facility': 'University of Colorado', 'geoPoint': {'lat': 39.72943, 'lon': -104.83192}}, {'zip': '63110', 'city': 'St Louis', 'state': 'Missouri', 'country': 'United States', 'facility': 'Washington University', 'geoPoint': {'lat': 38.62727, 'lon': -90.19789}}, {'zip': '29425', 'city': 'Charleston', 'state': 'South Carolina', 'country': 'United States', 'facility': 'Medical University of South Carolina; Hollings Cancer Center', 'geoPoint': {'lat': 32.77632, 'lon': -79.93275}}, {'zip': 'M5G 2M9', 'city': 'Toronto', 'state': 'Ontario', 'country': 'Canada', 'facility': 'University Health Network; Princess Margaret Hospital; Medical Oncology Dept', 'geoPoint': {'lat': 43.70643, 'lon': -79.39864}}, {'zip': 'H3T 1E2', 'city': 'Montreal', 'state': 'Quebec', 'country': 'Canada', 'facility': 'Jewish General Hospital / McGill University', 'geoPoint': {'lat': 45.50884, 'lon': -73.58781}}], 'overallOfficials': [{'name': 'Clinical Trials', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Hoffmann-La Roche'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Hoffmann-La Roche', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}