An Open-Label Study of Ruxolitinib Given With Chemotherapy in Patients With Advanced Solid Tumors

A Phase 1b Study of the Safety and Tolerability of Ruxolitinib in Combination With Gemcitabine With or Without Nab-Paclitaxel in Subjects With Advanced Solid Tumors

This is a study of ruxolitinib in combination with gemcitabine with or without nab-paclitaxel administered to patients with advanced or metastatic pancreatic cancer. The study will be conducted in two parts.

Part 1 of the study will evaluate the safety, tolerability and pharmacokinetics (PK) of ruxolitinib when given as described to patients with advanced or metastatic pancreatic cancer. A goal of Part 1 will be to identify the maximally tolerated dose (MTD) of ruxolitinib when given with gemcitabine with or without nab-paclitaxel. This dose will be selected for use in Part 2 of the study.

Part 2 of the study will further evaluate the safety, tolerability, PK and preliminary clinical activity of ruxolitinib at the dose defined in Part 1 used in combination with gemcitabine with or without nab-paclitaxel in subjects with advanced or metastatic pancreatic cancer.

After multiple challenges of trial conduct, by mutual agreement between investigators and sponsor, dose escalation ended after Cohort B1, RUX 10 mg twice daily (BID) - GCSF in October 2014. Therefore, the MTD was not reached. No safety issues led to the decision to stop further enrollment.

Because of the early study termination, samples for pharmacokinetics and pharmacodynamics, and computed tomography for tumor burden were collected, but not analyzed; analysis data are not available. The data cutoff for this posting is 22 SEP 2015. As of the data cutoff, 1 subject was receiving treatment in the study and had been enrolled for 47 weeks. This subject had their end of treatment visit in AUG 2016. A comparison of this subjects' safety data after the cutoff date showed no clinically meaningful differences (eg, adverse events) compared with safety results that are summarized here.

Inclusion Criteria:

• Male or female, 18 years or older

• Histologically or cytologically confirmed adenocarcinoma of the pancreas

• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1

• Requirements for prior therapy as outlined below:

  • Enrollment into Regimen A: received no more than 1 prior chemotherapy regimen for advanced or metastatic disease (not including neoadjuvant and/or adjuvant therapy)
  • Enrollment into Regimen B: received no prior chemotherapy for advanced or metastatic disease (not including neoadjuvant and/or adjuvant therapy)

• Adequate renal, hepatic, and bone marrow function without blood product or hematopoietic growth factor support:

• Able to swallow and retain oral medication

Exclusion Criteria:

• Any known contraindications to the use of gemcitabine (for enrollment in Regimen A or B) or nab-paclitaxel (for enrollment into Regimen B).
• Evidence of uncontrolled brain metastases or history of uncontrolled seizures.
• Ongoing radiation therapy and/or radiation therapy administered within 28 days of enrollment. Subjects who have received radiation to the spine, pelvis, ribs, or femur should be discussed with the sponsor, as extensive radiation to marrow forming region may compromise a subject's ability to tolerate myelosuppressive chemotherapy. Subjects who have ongoing radiotherapy-related toxicities are not eligible.
• Subjects who participated in any other study in which receipt of an investigational study drug occurred within 28 days or 5 half-lives (whichever is longer) prior to first dose.
• Current or previous other malignancy within 2 years of study entry, except cured basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix, or other noninvasive malignancy without sponsor approval.
• 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.
• Unwilling to be transfused with blood components.
• Known history of Hepatitis B or C infection or HIV infection.
• Presence of ≥ Grade 2 neuropathy