Clinical Trials /

Safety and Efficacy of MAK683 in Adult Patients With Advanced Malignancies

NCT02900651

Description:

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.

Related Conditions:
  • Borderline Ovarian Clear Cell Tumor
  • Diffuse Large B-Cell Lymphoma
  • Gastric Carcinoma
  • Nasopharyngeal Carcinoma
  • Prostate Carcinoma
  • Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Safety and Efficacy of MAK683 in Adult Patients With Advanced Malignancies
  • Official Title: A Phase I/II, Multicenter, Open-label Study of MAK683 in Adult Patients With Advanced Malignancies

Clinical Trial IDs

  • ORG STUDY ID: CMAK683X2101
  • SECONDARY ID: 2016-001860-12
  • NCT ID: NCT02900651

Conditions

  • Diffuse Large B-cell Lymphoma

Interventions

DrugSynonymsArms
MAK683Phase I - All

Purpose

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 will be to evaluate the anti-tumor activity of
      MAK683.
    

Trial Arms

NameTypeDescriptionInterventions
Phase I - AllExperimentaladvanced stage (relapsed/refractory or recurrent/metastatic) malignancy limited to the following malignancies; DLBCL, nasopharyngeal carcinoma, gastric cancer, ovarian cancer, prostate cancer and sarcoma.
  • MAK683

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of dose limiting toxicities (DLTs)
Time Frame:up to 28 days
Safety Issue:
Description:Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)

Secondary Outcome Measures

Measure:Overall Response Rate (ORR)
Time Frame:up to 30 months
Safety Issue:
Description:
Measure:Duration of overall response (DOR)
Time Frame:up to 30 months
Safety Issue:
Description:
Measure:Progression-free survival (PFS)
Time Frame:up to 30 months
Safety Issue:
Description:
Measure:Best Overall Response (BOR)
Time Frame:up to 30 months
Safety Issue:
Description:
Measure:Peak Plasma Concentration (Cmax) of MAK683
Time Frame:30 months
Safety Issue:
Description:Pharmacokinetic profile of MAK683
Measure:Area Under the Plasma Concentration (AUC) Time Curve of MAK683
Time Frame:30 months
Safety Issue:
Description:Pharmacokinetic profile of MAK683
Measure:Half-Life of MAK683
Time Frame:30 months
Safety Issue:
Description:Pharmacokinetic profile of MAK683
Measure:H3K27 tri methylation level in PBMC
Time Frame:up to day 15
Safety Issue:
Description:Cycle 1 Day 1,8,15 Cycle 2 Day1 Cycle 3 Day 1 End of treatment (EOT); Disease progression PBMC: peripheral blood mononuclear cell

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • MAK683, DLBCL, EED - Embryonic ectoderm development, EZH2 - Enhancer of zeste homolog 2

Last Updated

November 1, 2019