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

NCT01822756 | Terminated Phase 1 Results

• 1 other identifier: INCB 18424-144
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Solid Tumors; Pancreatic Cancer

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Adverse Events That Are Defined as Dose Limiting Toxicities (DLTs)

  Toxicities occurring during the first treatment cycle (Cycle 1) defined tolerability. Within each cohort, subjects were considered evaluable if they had received at least 40 of 56 planned doses of RUX during the 28-day surveillance period and received 2 of the 3 planned doses of chemotherapy (gemcitabine and/or gemcitabine and nab-paclitaxel) at the assigned dose level, or they had experienced a DLT.

  Approximately 28 days

Secondary Outcomes (6)

• Plasma Concentrations Will be Used to Estimate Peak Plasma Concentration (Cmax) and Area Under the Plasma Concentration Curve (AUC).

  Day 1 and Day 8

• Plasma Concentration of Tumor Specific Biomarkers and Cytokines Before and During Treatment.

  Up to 6 months

• Clinical Activity as Measured by the Greatest Decrease in Tumor Burden Compared to Baseline.

  Approximately 6 months

• Percentage of Participants With a Best Response by RECIST Criteria

  every 2 cycles starting at Cycle 3 Day 1 up to approximately 4 to 6 months

• Percentage of Responders

  Randomization to clinical cutoff 22Sept2015 (approx 244 days)

Study Arms (2)

Regimen A -ruxolitinib, gemcitabine

EXPERIMENTAL

Ruxolitinib (RUX) was self-administered by the subject orally in the morning and evening, approximately 12 hours apart, without regard to food. The morning dose of RUX was to be taken before the chemotherapy infusion, Gemcitabine IV, on days when they were given together (Days 1, 8, and 15 of each cycle).

Drug: ruxolitinib; Drug: gemcitabine

Regimen B-ruxolitinib, gemcitabine, nab-paclitaxel, filgrastim

EXPERIMENTAL

Ruxolitinib (RUX) was self-administered by the subject orally in the morning and evening, approximately 12 hours apart, without regard to food. Gemcitabine was provided as open-label, commercial product and was administered intravenously (IV) over 30 minutes on Days 1, 8, and 15 of each 28-day cycle. Reduced doses of gemcitabine administered IV over 30 minutes on Days 1, 8, and 15 of each 28-day cycle could also be explored. nab-Paclitaxel, as open-label, commercial product, was administered IV over 30 minutes on Days 1, 8, and 15 of each 28-day cycle.

Drug: ruxolitinib; Drug: gemcitabine; Drug: nab-paclitaxel; Drug: filgrastim

Interventions

ruxolitinib DRUG

Regimen A -ruxolitinib, gemcitabine; Regimen B-ruxolitinib, gemcitabine, nab-paclitaxel, filgrastim

gemcitabine DRUG

Other names: Gemzar®

Regimen A -ruxolitinib, gemcitabine; Regimen B-ruxolitinib, gemcitabine, nab-paclitaxel, filgrastim

nab-paclitaxel DRUG

Other names: Abraxane®

Regimen B-ruxolitinib, gemcitabine, nab-paclitaxel, filgrastim

filgrastim DRUG

Prophylactic GCSF support was filgrastim and was given in Cycle 1 on Days 2 to 5, 9 to 12, and 16 to 19, unless chemotherapy was held for toxicity, then prophylactic GCSF support was also held.

Also known as: Neupogen®

Regimen B-ruxolitinib, gemcitabine, nab-paclitaxel, filgrastim

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Incyte Corporation: lead

Study Sites (5)

Unknown Facility

Birmingham, Alabama, United States

Location

Unknown Facility

Gainesville, Florida, United States

Location

Unknown Facility

Sarasota, Florida, United States

Location

Unknown Facility

Durham, North Carolina, United States

Location

Unknown Facility

Nashville, Tennessee, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

ruxolitinib; Gemcitabine; 130-nm albumin-bound paclitaxel; Filgrastim

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Limitations and Caveats

In October 2014, further enrollment of additional study cohorts was stopped; Part 2 of the study wasn't conducted. Pharmacokinetic and Pharmacodynamics analyses weren't performed due to early termination. Maximum tolerated dose (MTD) was not reached.

Results Point of Contact

• Title: Study Director
• Organization: Incyte Corporation

1-855-463-3463

Study Officials

• Fitzroy Dawkins, M.D.

  Incyte Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2013
• First Posted: April 2, 2013
• Study Start: April 1, 2013
• Primary Completion: September 1, 2015
• Study Completion: August 1, 2016
• Last Updated: February 12, 2018
• Results First Posted: April 13, 2017

Record last verified: 2018-01

Locations

US (5)