Safety Study of Itacitinib (INCB039110) in Combination With Gemcitabine and Nab-Paclitaxel in Subjects With Advanced Solid Tumors

Study Overview
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Brief Summary
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Test the hypothesis that itacitinib (INCB039110) can be administered safely in combination with gemcitabine and nab-paclitaxel in subjects with advanced or metastatic cancer.

Detailed Description
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Study Part 1: This is a dose optimization phase designed to find a tolerated regimen that includes identifying the MTD of itacitinib (INCB039110) (within a defined pharmacologic range) in combination with doses of gemcitabine and nab-paclitaxel that have established safety and tolerability in subjects with advanced or metastatic solid tumors. Study Part 2 and Part 2A: This phase will explore the safety and tolerability of the MTD or PAD of itacitinib (INCB039110) when administered in combination with gemcitabine and nab-paclitaxel in subjects with untreated advanced or metastatic pancreatic cancer.

Official Title
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Official Title: A Phase 1B/2 Study of the Safety and Tolerability of Itacitinib (INCB039110) in Combination With Gemcitabine and Nab-Paclitaxel in Subjects With Advanced Solid Tumors

Conditions
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Solid Tumors, Pancreatic Cancer

Intervention / Treatment
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* Drug: itacitinib
* Drug: Gemcitabine
* Drug: nab-paclitaxel
* Drug: filgrastim


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed solid tumor (Part 1) or pancreatic adenocarcinoma (Part 2) Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 Received no more than 1 prior chemotherapy regimen for advanced or metastatic disease (not including neo-adjuvant and/or adjuvant therapy) (Part 1) Received no prior chemotherapy for advanced or metastatic disease (Part 2 and Part 2a) Adequate renal, hepatic, and bone marrow function without frequent blood product or hematopoietic growth factor support (eg use of erythropoietin or transfusions > 2 units packed red blood cells every 3 months) Ability to swallow and retain oral medication Exclusion Criteria: Any known contraindications to the use of a required comedication (gemcitabine or nab-paclitaxel). Evidence of uncontrolled brain metastases or history of uncontrolled seizures. Ongoing radiation therapy and/or radiation therapy administered within 28 days of enrollment or ongoing radiotherapy-related toxicities. Presence of ≥ Grade 2 neuropathy. Inability to swallow food or any condition of the upper GI tract that precludes administration of oral medications. Recent (≤ 3 months) history of partial or complete bowel obstruction. Unwillingness to be transfused with blood components. Known history of Hepatitis B or C infection or HIV infection

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: itacitinib, gemcitabine, nab-paclitaxel, filgrastim<br> | Drug: itacitinib<br> <br> * Other names: INCB039110;Drug: Gemcitabine<br> <br> * Other names: Gemzar®;Drug: nab-paclitaxel<br> <br> * Other names: Abraxane®;Drug: filgrastim<br> <br> * Other names: Neupogen®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of combination therapy study treatment itacitinib (INCB039110) plus nab-paclitaxel and gemcitabine as measured by the number of participants with adverse events |  | 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 (approximately 6 months). | 
| Identify the Maximum Tolerated Dose (MTD) or Pharmacologically Active Dose (PAD) within a defined dose range for itacitinib (INCB039110) in the treatment regimens administered |  | Each cohort will be observed for a minimum of 28 days. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of gemcitabine and paclitaxel administered with or without concurrent itacitinib (INCB039110) |  | Baseline up to 6 months. | 
| Clinical activity as measured by the greatest decrease in tumor burden compared to baseline. |  | Baseline and approximately every two cycles throughout the study until study completion or early termination (approximately 6 months). |