Clinical trial NCT01858883: Safety Study of Itacitinib (INCB039110) in Combination With Gemcitabine and Nab-Paclitaxel in Subjects With Advanced Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Solid Tumors
Pancreatic Cancer
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2013-05-21
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 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).
measure: Identify the Maximum Tolerated Dose (MTD) or Pharmacologically Active Dose (PAD) within a defined dose range for itacitinib (INCB039110) in the treatment regimens administered
timeFrame: Each cohort will be observed for a minimum of 28 days.
Secondary outcomes:
measure: Pharmacokinetics of gemcitabine and paclitaxel administered with or without concurrent itacitinib (INCB039110)
timeFrame: Baseline up to 6 months.
measure: Clinical activity as measured by the greatest decrease in tumor burden compared to baseline.
timeFrame: Baseline and approximately every two cycles throughout the study until study completion or early termination (approximately 6 months).
Other outcomes:
Locations:
city: Scottsdale
country: United States
state: Arizona
city: Fayetteville
country: United States
state: Arkansas
city: Beverly Hills
country: United States
state: California
city: Southington
country: United States
state: Connecticut
city: Indianapolis
country: United States
state: Indiana
city: Baltimore
country: United States
state: Maryland
city: Lake Success
country: United States
state: New York
city: Philadelphia
country: United States
state: Pennsylvania
Study officials:
affiliation: Incyte Corporation
name: Albert Assad, M.D.
role: STUDY_DIRECTOR
References:
citation: Beatty GL, Shahda S, Beck T, Uppal N, Cohen SJ, Donehower R, Gabayan AE, Assad A, Switzky J, Zhen H, Von Hoff DD. A Phase Ib/II Study of the JAK1 Inhibitor, Itacitinib, plus nab-Paclitaxel and Gemcitabine in Advanced Solid Tumors. Oncologist. 2019 Jan;24(1):14-e10. doi: 10.1634/theoncologist.2017-0665. Epub 2018 Aug 16.