Clinical trial NCT02900651: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Diffuse Large B-cell Lymphoma
Keywords: MAK683, DLBCL, EED - Embryonic ectoderm development, EZH2 - Enhancer of zeste homolog 2
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2016-09-14
Enrollment: 139
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Incidence of dose limiting toxicities (DLTs)
timeFrame: up to 28 days
measure: Safety and tolerability
timeFrame: up to approximately 3 years
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: up to 30 months
measure: Duration of overall response (DOR)
timeFrame: up to 30 months
measure: Progression-free survival (PFS)
timeFrame: up to 30 months
measure: Best Overall Response (BOR)
timeFrame: up to 30 months
measure: Peak Plasma Concentration (Cmax) of MAK683
timeFrame: 30 months
measure: Area Under the Plasma Concentration (AUC) Time Curve of MAK683
timeFrame: 30 months
measure: Half-Life of MAK683
timeFrame: 30 months
measure: H3K27 tri methylation level in PBMC
timeFrame: up to day 15
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF .
state: California
city: Santa Monica
country: United States
facility: UCLA Santa Monica Hematology Oncology
state: California
city: Houston
country: United States
facility: Uni Of TX MD Anderson Cancer Cntr Dept of Onc
state: Texas
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Chengdu
country: China
facility: Novartis Investigative Site
state: Sichuan
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Villejuif
country: France
facility: Novartis Investigative Site
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Koeln
country: Germany
facility: Novartis Investigative Site
city: Hong Kong
country: Hong Kong
facility: Novartis Investigative Site
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Rozzano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Fukuoka-city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Sunto Gun
country: Japan
facility: Novartis Investigative Site
state: Shizuoka
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
Study officials:
References: