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Terminated
The decision of early termination was made due to business reasons, and was not based on any safety or tolerability concerns for MAK683

Safety and Efficacy of MAK683 in Adult Patients With Advanced Malignancies

ClinicalTrials.gov ID NCT02900651
Sponsor Novartis Pharmaceuticals
Information provided by Novartis (Novartis Pharmaceuticals) (Responsible Party)
Last Update Posted 2024-10-31
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Study Overview

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.
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.

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Official Title
A Phase I/II, Multicenter, Open-label Study of MAK683 in Adult Patients With Advanced Malignancies
Conditions
Diffuse Large B-cell Lymphoma
Intervention / Treatment
  • Drug: MAK683
  • Drug: MAK683
Other Study ID Numbers
  • CMAK683X2101
  • 2016-001860-12 ( EudraCT Number )
    2016-001860-12 ( EudraCT Number )
Study Start (Actual)
2016-10-03
Primary Completion (Actual)
2024-10-09
Study Completion (Actual)
2024-10-09
Enrollment (Actual)
139
Study Type
Interventional
Phase
Phase 1

Contacts and Locations

This section provides contact details for people who can answer questions about joining this study, and information on where this study is taking place.

To learn more, please see the Contacts and Locations section in How to Read a Study Record(https://clinicaltrials.gov/study-basics/how-to-read-study-record#contacts-and-locations).

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.

For general information about clinical research, read Learn About Studies(https://clinicaltrials.gov/study-basics/learn-about-studies).
Eligibility Criteria
Description

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
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Ages Eligible for Study
18 Years and older (AdultOlder Adult )
Sexes Eligible for Study
All
Accepts Healthy Volunteers
No

Study Plan

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

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Design Details
Primary Purpose : Treatment
Allocation : Non-Randomized
Interventional Model : Single Group Assignment
Masking : None (Open Label)

Arms and Interventions

Participant Group/Arm Intervention/Treatment
Participant Group/Arm 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.
Intervention/Treatment Drug: MAK683
  • Drug: MAK683

Primary Outcome Measures
Outcome Measure Measure Description Time Frame
Incidence of dose limiting toxicities (DLTs)Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)up to 28 days
Safety and tolerabilityIncidence and severity of AEs, SAEs, changes in laboratory values, vital signs and ECGs, dose interruptions and reductionsup to approximately 3 years
Secondary Outcome Measures
Outcome Measure Measure Description Time Frame
Overall Response Rate (ORR) up to 30 months
Duration of overall response (DOR) up to 30 months
Progression-free survival (PFS) up to 30 months
Best Overall Response (BOR) up to 30 months
Peak Plasma Concentration (Cmax) of MAK683Pharmacokinetic profile of MAK68330 months
Area Under the Plasma Concentration (AUC) Time Curve of MAK683Pharmacokinetic profile of MAK68330 months
Half-Life of MAK683Pharmacokinetic profile of MAK68330 months
H3K27 tri methylation level in PBMCCycle 1 Day 1,8,15 Cycle 2 Day1 Cycle 3 Day 1 End of treatment (EOT); Disease progression PBMC: peripheral blood mononuclear cellup to day 15

Collaborators and Investigators

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

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 Registration Dates
First Submitted
2016-09-02
First Submitted that Met QC Criteria
2016-09-09
First Posted (Estimated)
2016-09-14
Study Record Updates
Last Update Submitted that met QC Criteria
2024-10-29
Last Update Posted
2024-10-31
Last Verified
2024-10

More Information

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Keywords Provided by Novartis (Novartis Pharmaceuticals)
Additional Relevant MeSH Terms

Plan to Share Individual Participant Data (IPD)?
No
IPD 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