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Safety and Efficacy of MAK683 in Adult Patients With Advanced Malignancies

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02900651
Recruitment Status : Active, not recruiting
First Posted : September 14, 2016
Last Update Posted : February 21, 2023
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Description
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Brief Summary:
The purpose of this Phase I/II study is to establish the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) and to evaluate the safety, antitumor activity and pharmacokinetic (PK) profile of MAK683 in patients with advanced malignancies such as Diffuse Large B cell Lymphoma (DLBCL), nasopharyngeal carcinoma (NPC) or other advanced solid tumors for whom no further effective standard treatment is available.

Condition or disease Intervention/treatment Phase
Diffuse Large B-cell Lymphoma Drug: MAK683 Phase 1

Detailed Description:

The purpose phase I of this trial is to characterize safety and tolerability and determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of MAK683.

The purpose of the phase II of this trial is to evaluate the anti-tumor activity of MAK683. Phase II part will not be opened.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 139 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II, Multicenter, Open-label Study of MAK683 in Adult Patients With Advanced Malignancies
Actual Study Start Date : October 3, 2016
Estimated Primary Completion Date : July 26, 2024
Estimated Study Completion Date : July 26, 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Phase I - All
advanced stage (relapsed/refractory or recurrent/metastatic) malignancy limited to the following malignancies; DLBCL, nasopharyngeal carcinoma, gastric cancer, ovarian cancer, prostate cancer and sarcoma.
 Drug: MAK683
Drug: MAK683


Outcome Measures
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Primary Outcome Measures :
  1. Incidence of dose limiting toxicities (DLTs) [ Time Frame: up to 28 days ]
    Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)

  2. Safety and tolerability [ Time Frame: up to approximately 3 years ]
    Incidence and severity of AEs, SAEs, changes in laboratory values, vital signs and ECGs, dose interruptions and reductions


Secondary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: up to 30 months ]
  2. Duration of overall response (DOR) [ Time Frame: up to 30 months ]
  3. Progression-free survival (PFS) [ Time Frame: up to 30 months ]
  4. Best Overall Response (BOR) [ Time Frame: up to 30 months ]
  5. Peak Plasma Concentration (Cmax) of MAK683 [ Time Frame: 30 months ]
    Pharmacokinetic profile of MAK683

  6. Area Under the Plasma Concentration (AUC) Time Curve of MAK683 [ Time Frame: 30 months ]
    Pharmacokinetic profile of MAK683

  7. Half-Life of MAK683 [ Time Frame: 30 months ]
    Pharmacokinetic profile of MAK683

  8. H3K27 tri methylation level in PBMC [ Time Frame: up to day 15 ]
    Cycle 1 Day 1,8,15 Cycle 2 Day1 Cycle 3 Day 1 End of treatment (EOT); Disease progression PBMC: peripheral blood mononuclear cell


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

Inclusion Criteria:

  1. Eastern Cooperative Oncology Group (ECOG): 0 to 2
  2. Relapsed or refractory diffuse large B cell lymphoma with measurable disease as determined by Non-Hodgkin's Lymphoma Cheson response criteria (2014)
  3. Advanced or recurrent/metastatic solid tumor, including nasopharyngeal carcinoma, castration-resistant prostate cancer, gastric cancer, ovarian clear cell carcinoma and sarcoma, with measurable disease as determined by RECIST 1.1.

Exclusion Criteria:

  1. Other malignant diseases than the ones being treated in this study
  2. Severe and/or uncontrolled medical conditions that in the investigator's opinion could affect the safety of individual or impair the assessment of study result.
  3. B-cell lymphoma patients who have received prior allogeneic stem cell transplant
  4. Patient have received anti-cancer therapies within defined time frames prior to the first dose of study treatment
  5. Symptomatic central nervous system (CNS) involvement which are neurologically unstable or requiring increasing doses of steroids to control.
  6. Patient having out of range laboratory values defined as:

1) Insufficient bone marrow function at screening:

  • Platelets ≤ 50,000/mm3
  • Hemoglobin (Hgb) ≤ 80 g/L
  • Absolute neutrophil count (ANC) ≤ 1000/mm3 2) Insufficient hepatic and renal function at screening:
  • ALP, ALT, and AST > 3 x ULN (>5 x ULN if subject has liver metastases)
  • Total bilirubin >1.5 x ULN
  • Serum creatinine > 1.5 x ULN and/or creatinine clearance ≤ 50 mL/min
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02900651


Locations
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United States, California
University of California San Francisco
San Francisco, California, United States, 94115
UCLA Santa Monica Hematology / Oncology
Santa Monica, California, United States, 90404
United States, Texas
University of Texas MD Anderson Cancer Center Dept of Onc
Houston, Texas, United States, 77030
Canada, Ontario
Novartis Investigative Site
Toronto, Ontario, Canada, M5G 2M9
China, Shanghai
Novartis Investigative Site
Shanghai, Shanghai, China, 200032
China, Sichuan
Novartis Investigative Site
Chengdu, Sichuan, China, 610041
France
Novartis Investigative Site
Villejuif Cedex, Île-de-France, France, 94800
Germany
Novartis Investigative Site
Freiburg, Germany, 79106
Novartis Investigative Site
Koeln, Germany, 50937
Hong Kong
Novartis Investigative Site
Hong Kong, Hong Kong
Italy
Novartis Investigative Site
Milano, MI, Italy, 20133
Novartis Investigative Site
Rozzano, MI, Italy, 20089
Japan
Novartis Investigative Site
Fukuoka-city, Fukuoka, Japan, 811-1395
Novartis Investigative Site
Sunto Gun, Shizuoka, Japan, 411 8777
Singapore
Novartis Investigative Site
Singapore, Singapore, 169610
Spain
Novartis Investigative Site
Madrid, Spain, 28041
Sponsors and Collaborators
Novartis Pharmaceuticals
More Information
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02900651    
Other Study ID Numbers: CMAK683X2101
2016-001860-12 ( EudraCT Number )
First Posted: September 14, 2016    Key Record Dates
Last Update Posted: February 21, 2023
Last Verified: February 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
MAK683, DLBCL, EED - Embryonic ectoderm development, EZH2 - Enhancer of zeste homolog 2
Additional relevant MeSH terms:
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Lymphoma, Large B-Cell, Diffuse
Neoplasms
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Lymphoma
 Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases