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Open-Label Safety and Tolerability Study of INCB057643 in Subjects 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: NCT02711137
Recruitment Status : Terminated (Study terminated due to safety issues.)
First Posted : March 17, 2016
Last Update Posted : December 10, 2019
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

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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
Actual Primary Completion Date : February 13, 2019
Actual Study Completion Date : February 13, 2019


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. 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 ]


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
Show Show 18 study locations
Sponsors and Collaborators
Incyte Corporation
Investigators
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Study Director: Fred Zheng, MD, PhD Incyte Corporation

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Responsible Party: Incyte Corporation
ClinicalTrials.gov Identifier: NCT02711137    
Other Study ID Numbers: INCB 57643-101
First Posted: March 17, 2016    Key Record Dates
Last Update Posted: December 10, 2019
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Incyte Corporation:
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)
NUT midline carcinoma
non-Hodgkin lymphoma
diffuse large B-cell lymphoma (DLBCL)
double-hit
triple-hit
myc
bromodomain and extra-terminal (BET) inhibitor
Additional relevant MeSH terms:
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Neoplasms
Gemcitabine
Azacitidine
Rucaparib
Antineoplastic Agents
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Poly(ADP-ribose) Polymerase Inhibitors