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Trial record 6 of 8 for:    nut midline carcinoma

Open-Label Safety and Tolerability Study of INCB057643 in Subjects With Advanced Malignancies

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ClinicalTrials.gov Identifier: NCT02711137
Recruitment Status : Active, not recruiting
First Posted : March 17, 2016
Last Update Posted : May 17, 2018
Sponsor:
Information provided by (Responsible Party):
Incyte Corporation

Brief Summary:

The purpose of the Study is to select a dose and assess the safety and tolerability of INCB057643 as a monotherapy (Part 1 and Part 2) and in combination with standard-of-care (SOC) agents (Part 3 and Part 4) for subjects with advanced malignancies.

Part 1 will determine the maximum tolerated dose of INCB057643 and/or a tolerated dose that demonstrates sufficient pharmacologic activity. Part 2 will further evaluate the safety, preliminary efficacy, PK, and PD of the dose(s) selected in Part 1 in select tumor types including solid tumors, lymphomas and other hematologic malignancies. Part 3 will determine the tolerated dose of INCB057643 in combination with select SOC agents; and assess the safety and tolerability of the combination therapy in select advanced solid tumors and hematologic malignancies. Part 4 will further evaluate the safety, preliminary efficacy, PK, and PD of the selected dose combination from Part 3 in 4 specific advanced solid tumor and hematologic malignancies.


Condition or disease Intervention/treatment Phase
Solid Tumors Drug: INCB057643 Drug: Gemcitabine Drug: Paclitaxel Drug: Rucaparib Drug: Abiraterone Drug: Ruxolitinib Drug: Azacitidine Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 136 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2, Open-Label, Dose-Escalation/Dose-Expansion, Safety and Tolerability Study of INCB057643 in Subjects With Advanced Malignancies
Study Start Date : May 2016
Estimated Primary Completion Date : November 2018
Estimated Study Completion Date : December 2018


Arm Intervention/treatment
Experimental: INCB057643 Drug: INCB057643
Initial cohort dose of INCB057643 at the protocol-specified starting dose (Part 1), with subsequent dose escalations based on protocol-specific criteria. The recommended treatment group-specific dose(s) will be taken forward into expansion cohorts (Part 2).

Experimental: INCB057643 + Standard of Care (SOC) agents Drug: INCB057643
Initial cohort dose of INCB057643 at the protocol-specified starting dose (Part 3), with subsequent dose escalations based on protocol-specific criteria. The recommended treatment group-specific dose(s) will be taken forward into expansion cohorts (Part 4).

Drug: Gemcitabine
Standard of Care (SOC) agents

Drug: Paclitaxel
Standard of Care (SOC) agents

Drug: Rucaparib
Standard of Care (SOC) agents

Drug: Abiraterone
Standard of Care (SOC) agents

Drug: Ruxolitinib
Standard of Care (SOC) agents

Drug: Azacitidine
Standard of Care (SOC) agents




Primary Outcome Measures :
  1. Safety and tolerability of INCB057643 as monotherapy and in combination with standard of care (SOC) agents in patients with advanced malignancies; assessed by clinical laboratory assessments, physical examinations, 12 lead ECGs, and adverse events (AEs) [ Time Frame: From screening through at least 30 days after end of treatment, up to approximately 24 months ]

Secondary Outcome Measures :
  1. Pharmacokinetics of INCB057643 as monotherapy in the fasted state and in the fed state (food effect; Part 2 only) and when administered in combination with Standard of Care (SOC) agents in the fasted state assessed by plasma and urine concentrations [ Time Frame: Protocol-defined timepoints in treatment Cycle 1 and 2, up to approximately 1 month. ]
  2. Measurement of cellular myc protein concentrations before and after administration of INCB057643 when administered as monotherapy [ Time Frame: PD in plasma at pre-dose and 0.5, 1, 2, 4, 6 and 8 hours postdose, up to approximately 1 month. ]
  3. Identify cell populations and changes in cell populations, including, but not limited to, markers for tumor cell or immune cell populations before and after administration of INCB057643 when administered as monotherapy [ Time Frame: Sparse correlative whole blood and plasma up to approximately 24 months. ]
  4. Efficacy of INCB057643 when administered as monotherapy and in combination with SOC agents based on the investigator assessment of response using criteria appropriate for each disease in subjects with advanced malignancies criteria [ Time Frame: Efficacy measures from screening through end of treatment and follow-up (every 9 weeks), up to approximately 24 months ]
  5. Measurement of biomarkers that may predict pharmacologic activity or response to INCB57643 when administered as monotherapy and in combination with SOC agents criteria [ Time Frame: Efficacy measures from screening through end of treatment and follow-up (every 9 weeks), up to approximately 24 months ]
  6. Efficacy assessed by progression-free survival (PFS) or event-free survival (EFS) per disease-specific response criteria [ Time Frame: Efficacy measures from screening through end of treatment and follow-up (every 9 weeks), up to approximately 24 months ]
  7. Efficacy assessed by duration of response (DOR) per disease-specific response criteria [ Time Frame: Efficacy measures from screening through end of treatment and follow-up (every 9 weeks), up to approximately 24 months ]
  8. Efficacy assessed by overall survival (OS) per disease-specific response criteria [ Time Frame: Efficacy measures from screening through end of treatment and follow-up (every 9 weeks), up to approximately 24 months ]
  9. Subjects' self-reported myelofibrosis (MF)-related symptom burden assessment in subjects with MF after administration of INCB057643 in combination with ruxolitinib. [ Time Frame: Protocol-defined time points up to approximately 24 months. ]


Information from the National Library of Medicine

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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:

  • Histologically or cytologically confirmed diagnosis of relapsed or refractory advanced or metastatic malignancies:

    • Part 1: solid tumors or lymphomas, or hematologic malignancies
    • Part 2: histologically confirmed disease in specific tumor types
    • Part 3: advanced solid tumor or hematologic malignancy
    • Part 4: select advanced solid tumor or hematologic malignancy
  • For Part 1 and 2, subjects must have progressed following at least 1 line of prior therapy and there is no further established therapy that is known to provide clinical benefit (including subjects who are intolerant to the established therapy)
  • For Parts 3 and 4, subjects must have progressed following at least 1 line of prior therapy, and the treatment with the select SOC agent is relevant for the specific disease cohort.
  • Life expectancy > 12 weeks, for MF subjects in Parts 3 and 4, life expectancy > 24 weeks
  • Eastern Cooperative Oncology Group (ECOG) performance status

    • Parts 1 and 3: 0 or 1
    • Parts 2 and 4: 0, 1, or 2
  • Willingness to avoid pregnancy or fathering children

Exclusion Criteria:

  • Inadequate bone marrow function per protocol-specified hemoglobin, platelet count, and absolute neutrophil count
  • Inadequate organ function per protocol-specified total bilirubin, AST and ALT, creatinine clearance and alkaline phosphatase.
  • Receipt of anticancer medications or investigational drugs within protocol-specified intervals
  • Unless approved by the medical monitor, may not have received an allogeneic hematopoietic stem cell transplant within 6 months before treatment, or have active graft-versus-host-disease following allogeneic transplant
  • Unless approved by the medical monitor, may not have received autologous hematopoietic stem cell transplant within 3 months before treatment
  • Any unresolved toxicity ≥ Grade 2 (except stable Grade 2 peripheral neuropathy or alopecia) from previous anticancer therapy
  • Radiotherapy within the 2 weeks before initiation of treatment. Palliative radiation treatment to nonindex or bone lesions performed less than 2 weeks before treatment initiation may be considered with medical monitor approval
  • Currently active and uncontrolled infectious disease requiring systemic antibiotic, antifungal, or antiviral treatment
  • Untreated brain or central nervous system (CNS) metastases or brain/CNS metastases that have progressed
  • History or presence of abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful
  • Type 1 diabetes or uncontrolled Type 2 diabetes
  • HbA1c of ≥ 8% (all subjects will have HbA1c test at screening)
  • Any sign of clinically significant bleeding
  • Coagulation panel within protocol-specified parameters

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): NCT02711137


Locations
United States, Alabama
University of Alabama
Birmingham, Alabama, United States, 35294-3300
United States, California
University of California
La Jolla, California, United States, 92093
United States, Colorado
Sarah Cannon Research Institute at Health One
Denver, Colorado, United States, 80218
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06510
United States, Florida
Sylvester Comprehensive Cancer Center
Miami, Florida, United States, 33136
Hematology - Oncology Associates of Treasure Coast
Port Saint Lucie, Florida, United States, 34952
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Washington University
Saint Louis, Missouri, United States, 63110
United States, New York
University of Rochester, Wilmot Cancer Center
Rochester, New York, United States, 14642
United States, North Carolina
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 27599
Wake Forest Baptist Health
Winston-Salem, North Carolina, United States, 27157
United States, Texas
Oncology Consultants, P.A.
Houston, Texas, United States, 77030
The Methodist Hospital
Houston, Texas, United States, 77030
United States, Utah
Huntsman Cancer Institute
Salt Lake City, Utah, United States, 84112
United States, Washington
MultiCare Institute for Research and Innovation
Tacoma, Washington, United States, 98405
Belgium
Institut Jules Bordet, Clinical Trial Conduct Unit
Brussels, Belgium, B-1000
France
HÔPITAL SAINT-LOUIS, Service Hématologie Adultes
Paris, France, 75010
Sponsors and Collaborators
Incyte Corporation
Investigators
Study Director: Fred Zheng, MD, PhD Incyte Corporation

Responsible Party: Incyte Corporation
ClinicalTrials.gov Identifier: NCT02711137     History of Changes
Other Study ID Numbers: INCB 57643-101
First Posted: March 17, 2016    Key Record Dates
Last Update Posted: May 17, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Incyte Corporation:
NUT midline carcinoma
Solid tumor
lymphoma
leukemia
AML
myelodysplastic syndrome (MDS)
multiple myeloma
myeloproliferative neoplasm (MPN)
MDS/MPN
myelofibrosis (MF)
pancreatic cancer
colorectal cancer
non-small cell lung cancer
prostate cancer
breast cancer
ovarian cancer
glioblastoma multiforme (GBM)
non-Hodgkin lymphoma
diffuse large B-cell lymphoma (DLBCL)
double-hit
triple-hit
myc
bromodomain and extra-terminal (BET) inhibitor

Additional relevant MeSH terms:
Gemcitabine
Azacitidine
Rucaparib
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Poly(ADP-ribose) Polymerase Inhibitors