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An Open-Label Study of a Novel JAK-inhibitor, INCB047986, Given in Patients With Advanced Malignancies

Primary Purpose

Solid Tumor, Hodgkin's Lymphoma, NHL (Non-Hodgkin Lymphoma)

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

INCB047986

Gemcitabine

nab-paclitaxel

About this trial

This is an interventional treatment trial for Solid Tumor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Group 1

Aged 18 years or older, with histologically or cytologically confirmed solid tumor, Hodgkin's lymphoma, aggressive or indolent non-Hodgkin's lymphoma. (NOTE: Patients with acute and chronic leukemia, Burkitt's lymphoma, precursor B lymphoblastic leukemia/lymphoma, and myeloma are excluded)
Life expectancy of 12 weeks or longer.
Subject must have received ≥ 1 prior treatment regimen.
The subject must not be a candidate for potentially curative therapy, including transplant.

Group 2

Aged 18 years or older
Part 1 - Histologically or cytologically confirmed pancreatic adenocarcinoma (first or second line), triple-negative breast cancer (second line), or urothelial cancer (second line)
Part 2 - Histologically or cytologically confirmed pancreatic adenocarcinoma
No more than 1 prior chemotherapy regimen for advanced or metastatic disease (not including neoadjuvant and/or adjuvant therapy).
There is no restriction on the number of prior non-myelosuppressive targeted therapies or hormonal agents (e.g., epidermal growth factor receptor-targeted therapy for lung cancer and hormonal therapy for breast cancer or ovarian cancer); NOTE: Targeted and/or hormonal therapy alone will not be considered chemotherapy for the purposes of this study.

Exclusion Criteria:

Group 1 and 2

Received an investigational study drug within 28 days or 5 half-lives (whichever is longer) prior to receiving their first dose of study drug.
Received any approved anticancer medications within 21 days or 5 half-lives (whichever is longer) prior to receiving the first dose of study drug (42 days for nitrosoureas) EXCEPT steroids at ≤ 10 mg prednisone daily (or equivalent).
Has any unresolved toxicity ≥ Grade 2 from previous anticancer therapy without medical monitor approval.
o Subjects with ongoing chronic toxicities such as fatigue or neuropathy may be allowed after approval from the sponsor's medical monitor
Evidence of uncontrolled brain metastases or history of spinal cord compression, or primary central nervous system (CNS) tumors.
Has an Eastern Cooperative Oncology Group (ECOG) performance status of ≥ 2.
Received allogeneic hematopoietic stem cell transplant within the last 6 months, or has active graft versus host disease (GVHD) following allogeneic transplant, or is currently receiving immunosuppressive therapy following allogeneic transplant.
Received autologous hematopoietic stem cell transplant within the last 3 months.
Radiation treatment within the previous 4 weeks.
History of active hepatitis or positive serology for hepatitis B (unless due to vaccination) or C

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Group 1 INCB047986

Group 2 Experimental: INCB047986, gemcitabine, nab-paclitaxel

Arm Description

Outcomes

Primary Outcome Measures

Adverse events that are defined as dose limiting toxicities occurring in the first 21 days of treatment in Group 1 and the first 28 days of treatment in Group 2.

Safety and tolerability of INCB047986 monotherapy and in combination with gemcitabine and nab-paclitaxel as assessed by summary of clinical laboratory assessments, Electrocardiogram (ECG), and Adverse Events (AEs).

Group 1: Baseline and weekly for Cycle 1 and then Day 1 for all subsequent cycles until the End of Treatment visit. Group 2: Baseline and weekly for Cycle 1 and then Day 1, Week 8 and Week 15 for all subsequent cycles until the End of Treatment visit.

Secondary Outcome Measures

Tumor response rates will be derived from investigator assessment of response in subjects with measurable disease

Plasma concentrations will be used to estimate peak plasma concentration (cmax) and area under the plasma concentration curve (AUC)

Duration of Response (DOR) and Progression Free Survival (PFS) in subjects with measureable disease

Plasma concentration of biomarkers and cytokines before and during treatment

Change in body weight

Change in Eastern Cooperative Oncology Group (ECOG) status from baseline to each visit where the variable is measured

Full Information

NCT ID

NCT01929941

First Posted

August 22, 2013

Last Updated

January 15, 2018

Sponsor

Incyte Corporation

1. Study Identification

Unique Protocol Identification Number

NCT01929941

Brief Title

An Open-Label Study of a Novel JAK-inhibitor, INCB047986, Given in Patients With Advanced Malignancies

Official Title

A Phase 1, Open-Label, Dose-Escalation, Safety and Tolerability Study of INCB047986 in Subjects With Advanced Malignancies

Study Type

Interventional

2. Study Status

Record Verification Date

January 2018

Overall Recruitment Status

Terminated

Why Stopped

Business decision.

Study Start Date

September 2013 (undefined)

Primary Completion Date

August 2014 (Actual)

Study Completion Date

August 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Incyte Corporation

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

This is an open-label study of INCB047986 given to two distinct groups of patients (Group 1 and Group 2) with advanced malignancies. The purpose of the study is to evaluate the safety, tolerability and pharmacokinetics of INCB047986 and to determine the maximum tolerated dose of INCB047986 in combination with gemcitabine and nab paclitaxel in a select group of patients with solid tumors. Each patient group will participate in a phase of the study which is divided into two parts. The patient groups will be enrolled in a sequential manner starting with Patient Group 1. Patient Group 1 Group 1 will be comprised of patients with advanced malignancies who will receive INCB047986 as monotherapy. Part 1: Dose Escalation Phase - This phase will evaluate the safety, tolerability and pharmacokinetics (PK) of INCB047986 when given as described to patients with advanced malignancies. A goal of Part 1 will be to identify the maximally tolerated dose (MTD) of INCB047986 and/or other dose(s) that are tolerated doses and produce a substantial pharmacologic effect. These doses will be used in Part 2 of the study. Part 2: Expansion Phase - This phase will further explore the safety, tolerability, PK, and preliminary clinical activity of INCB047986 using the doses identified in Part 1. Group 2 Group 2 will be in subjects with advanced or metastatic pancreatic cancer, breast cancer or urothelial cancer. Part 1: Dose Optimization Phase - This phase will identify the MTD of INCB047986 in combination with gemcitabine and nab-paclitaxel in patients with advanced or metastatic solid tumors. Specifically, these will be patients with pancreatic adenocarcinoma (first or second line), triple-negative breast cancer (second line) or urothelial cancer (second line). Part 2: Expansion Phase - This phase will explore the safety, tolerability, PK, biomarkers, and preliminary clinical activity of the dose regimen(s) identified in Part 1. Patients enrolled in this phase will be limited to those with advanced or metastatic pancreatic cancer.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Solid Tumor, Hodgkin's Lymphoma, NHL (Non-Hodgkin Lymphoma), Pancreatic Cancer, Breast Cancer, UC (Ureter and Urethera), Advanced Cancer, Metastatic Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

5 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Group 1 INCB047986

Arm Type

Experimental

Arm Title

Group 2 Experimental: INCB047986, gemcitabine, nab-paclitaxel

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

INCB047986

Intervention Description

Initial cohort dose of INCB047986 monotherapy at the protocol-specified starting dose, with subsequent cohort escalations based on protocol-specific criteria

Intervention Type

Drug

Intervention Name(s)

INCB047986

Intervention Description

INCB047986 tablets administered orally at the protocol specified dose and frequency

Intervention Type

Drug

Intervention Name(s)

Gemcitabine

Other Intervention Name(s)

Gemzar®

Intervention Description

Gemcitabine administered intravenously over 30 minutes at the protocol-specified dose and frequency

Intervention Type

Drug

Intervention Name(s)

nab-paclitaxel

Other Intervention Name(s)

Abraxane®

Intervention Description

nab-paclitaxel administered intravenously over 30 minutes at the protocol-specified dose and frequency

Primary Outcome Measure Information:

Title

Adverse events that are defined as dose limiting toxicities occurring in the first 21 days of treatment in Group 1 and the first 28 days of treatment in Group 2.

Time Frame

Approximately 21 days (Group 1); Approximately 28 days (Group 2)

Title

Description

Time Frame

Group 1 and Group 2: up to 6 months

Secondary Outcome Measure Information:

Title

Tumor response rates will be derived from investigator assessment of response in subjects with measurable disease

Time Frame

Approximately 6 months

Title

Plasma concentrations will be used to estimate peak plasma concentration (cmax) and area under the plasma concentration curve (AUC)

Time Frame

Day 15 of treatment at a given dose

Title

Duration of Response (DOR) and Progression Free Survival (PFS) in subjects with measureable disease

Time Frame

Approximately 6 months

Title

Plasma concentration of biomarkers and cytokines before and during treatment

Time Frame

Approximately 6 months

Title

Change in body weight

Time Frame

Approximately 6 months

Title

Change in Eastern Cooperative Oncology Group (ECOG) status from baseline to each visit where the variable is measured

Time Frame

Approximately 6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Group 1 Aged 18 years or older, with histologically or cytologically confirmed solid tumor, Hodgkin's lymphoma, aggressive or indolent non-Hodgkin's lymphoma. (NOTE: Patients with acute and chronic leukemia, Burkitt's lymphoma, precursor B lymphoblastic leukemia/lymphoma, and myeloma are excluded) Life expectancy of 12 weeks or longer. Subject must have received ≥ 1 prior treatment regimen. The subject must not be a candidate for potentially curative therapy, including transplant. Group 2 Aged 18 years or older Part 1 - Histologically or cytologically confirmed pancreatic adenocarcinoma (first or second line), triple-negative breast cancer (second line), or urothelial cancer (second line) Part 2 - Histologically or cytologically confirmed pancreatic adenocarcinoma No more than 1 prior chemotherapy regimen for advanced or metastatic disease (not including neoadjuvant and/or adjuvant therapy). There is no restriction on the number of prior non-myelosuppressive targeted therapies or hormonal agents (e.g., epidermal growth factor receptor-targeted therapy for lung cancer and hormonal therapy for breast cancer or ovarian cancer); NOTE: Targeted and/or hormonal therapy alone will not be considered chemotherapy for the purposes of this study. Exclusion Criteria: Group 1 and 2 Received an investigational study drug within 28 days or 5 half-lives (whichever is longer) prior to receiving their first dose of study drug. Received any approved anticancer medications within 21 days or 5 half-lives (whichever is longer) prior to receiving the first dose of study drug (42 days for nitrosoureas) EXCEPT steroids at ≤ 10 mg prednisone daily (or equivalent). Has any unresolved toxicity ≥ Grade 2 from previous anticancer therapy without medical monitor approval. o Subjects with ongoing chronic toxicities such as fatigue or neuropathy may be allowed after approval from the sponsor's medical monitor Evidence of uncontrolled brain metastases or history of spinal cord compression, or primary central nervous system (CNS) tumors. Has an Eastern Cooperative Oncology Group (ECOG) performance status of ≥ 2. Received allogeneic hematopoietic stem cell transplant within the last 6 months, or has active graft versus host disease (GVHD) following allogeneic transplant, or is currently receiving immunosuppressive therapy following allogeneic transplant. Received autologous hematopoietic stem cell transplant within the last 3 months. Radiation treatment within the previous 4 weeks. History of active hepatitis or positive serology for hepatitis B (unless due to vaccination) or C

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

William Williams, M.D.

Organizational Affiliation

Incyte Corporation

Official's Role

Study Director

Facility Information:

City

Atlanta

State/Province

Georgia

Country

United States

City

Nashville

State/Province

Tennessee

Country

United States

City

Dallas

State/Province

Texas

Country

United States

12. IPD Sharing Statement

Learn more about this trial

An Open-Label Study of a Novel JAK-inhibitor, INCB047986, Given in Patients With Advanced Malignancies

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