Solid TumorsPhase 1NCT01822756
An Open-Label Study of Ruxolitinib Given With Chemotherapy in Patients With Advanced Solid Tumors
A Phase 1 study testing ruxolitinib, gemcitabine and nab-paclitaxel in people with Solid Tumors and Pancreatic Cancer, run by Incyte Corporation at 5 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors, Pancreatic Cancer
- What is being tested?
- ruxolitinib, gemcitabine and nab-paclitaxel
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 5 sitesUnited States
- Study dates
- Apr 2013to Aug 2016
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 10Show fewer
- 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
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Study site
Birmingham, Alabama
Study site
Durham, North Carolina
Study site
Gainesville, Florida
Study site
Nashville, Tennessee
Study site
Sarasota, Florida
About this study
Official title: 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.
Read more
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
- Being tested
- ruxolitinib, gemcitabine, nab-paclitaxel, filgrastim
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ruxolitinibDrug
gemcitabineDrug
Other names: Gemzar®
nab-paclitaxelDrug
Other names: Abraxane®
filgrastimDrug
Also called Neupogen®
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.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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. Receives: Drug: ruxolitinib; Drug: gemcitabine; Drug: nab-paclitaxel; Drug: filgrastim |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
Measured: Day 1 and Day 8
Plasma Concentration of Tumor Specific Biomarkers and Cytokines Before and During Treatment.
Measured: Up to 6 months
Clinical Activity as Measured by the Greatest Decrease in Tumor Burden Compared to Baseline.
Measured: Approximately 6 months
Percentage of Participants With a Best Response by RECIST Criteria
Best response was determined on the subject level using the highest overall response achieved post-baseline. In the case of stable disease (SD), measurements had to meet the SD criterion at least once after study entry at a minimum interval of 49 days. Subjects who failed to meet this criterion had best response of progressive disease (PD) if the next available RECIST evaluation after the initial scan indicated PD or not evaluable (NE) if no additional RECIST evaluations were available.
Complete Response (CR) and Partial Response (PR) defined by the Response Evaluation Criteria in Solid Tumor (RECIST) criteria. CR: Disappearance of all target and nontarget lesions. PR: At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter, or persistence of 1 or more nontarget lesion(s) or/and maintenance of tumor marker level above the normal limits.
Measured: every 2 cycles starting at Cycle 3 Day 1 up to approximately 4 to 6 months
Percentage of Responders
Duration of response was measured as the time from the first overall response contributing to an objective response to the first overall response of progressive disease (PD) occurring after the first overall response contributing to the objective response.
Measured: Randomization to clinical cutoff 22Sept2015 (approx 244 days)
Duration of Response
Duration of response was the time from the first overall response contributing to an objective response to the first overall response of progressive disease (PD) occurring after the first overall response contributing to the objective response. Confidence intervals for median duration of response were calculated using the method of Brookmeyer and Crowley (1982).
Measured: Randomization to clinical cutoff 22Sept2015 (approx 244 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2013 (estimated)
- Study startApr 2013
- Primary completionSep 2015
- Study completionAug 2016
Why it stopped: Dose escalation ended after Cohort B1, RUX 10 mg BID - GCSF in October 2014.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Solid TumorsStudies of the same condition, open and under way.
- More trials run by Incyte CorporationThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Incyte Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Fitzroy Dawkins, M.D., Study director, Incyte Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01822756
- Sponsor's protocol ID
- INCB 18424-144
- Status last verified
- Jan 2018
- First submitted
- 28 Mar 2013
- Last updated
- 12 Feb 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01822756
- Acronym / sponsor ID
- INCB 18424-144
- Conditions
- Solid Tumors, Pancreatic Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Dose escalation ended after Cohort B1, RUX 10 mg BID - GCSF in October 2014.
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Incyte CorporationIndustry (pharma, biotech, devices)
- Study start
- Apr 2013
- Primary completion
- Sep 2015 (actual)
- Study completion
- Aug 2016 (actual)
- First posted
- 2 Apr 2013 (estimated)
- Results
- Posted 13 Apr 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Regimen A -ruxolitinib, gemcitabine | Experimental | Drug: ruxolitinib, Drug: gemcitabineRuxolitinib (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). |
| Regimen B-ruxolitinib, gemcitabine, nab-paclitaxel, filgrastim | Experimental | Drug: ruxolitinib, Drug: gemcitabine, Drug: nab-paclitaxel, Drug: filgrastimRuxolitinib (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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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:
- Adequate renal, hepatic, and bone marrow function without blood product or hematopoietic growth factor support:
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ruxolitinib | Drug | Regimen A -ruxolitinib, gemcitabine, Regimen B-ruxolitinib, gemcitabine, nab-paclitaxel, filgrastim |
| gemcitabineOther names: Gemzar® | Drug | Regimen A -ruxolitinib, gemcitabine, Regimen B-ruxolitinib, gemcitabine, nab-paclitaxel, filgrastim |
| nab-paclitaxelOther names: Abraxane® | Drug | Regimen B-ruxolitinib, gemcitabine, nab-paclitaxel, filgrastim |
| filgrastimAlso: Neupogen®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. | Drug | Regimen B-ruxolitinib, gemcitabine, nab-paclitaxel, filgrastim |
Primary outcome
Percentage of Participants With Adverse Events That Are Defined as Dose Limiting Toxicities (DLTs)
Time frame: Approximately 28 days
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.
6 secondary outcomes
Plasma Concentrations Will be Used to Estimate Peak Plasma Concentration (Cmax) and Area Under the Plasma Concentration Curve (AUC).
Time frame: Day 1 and Day 8
Plasma Concentration of Tumor Specific Biomarkers and Cytokines Before and During Treatment.
Time frame: Up to 6 months
Clinical Activity as Measured by the Greatest Decrease in Tumor Burden Compared to Baseline.
Time frame: Approximately 6 months
Percentage of Participants With a Best Response by RECIST Criteria
Time frame: every 2 cycles starting at Cycle 3 Day 1 up to approximately 4 to 6 months
Percentage of Responders
Time frame: Randomization to clinical cutoff 22Sept2015 (approx 244 days)
Duration of Response
Time frame: Randomization to clinical cutoff 22Sept2015 (approx 244 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Fitzroy Dawkins, M.D. study director
Incyte Corporation
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ruxolitinib, gemcitabine and nab-paclitaxel in people with Solid Tumors and Pancreatic Cancer, run by Incyte Corporation at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 12 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Apr 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Adverse Events That Are Defined as Dose Limiting Toxicities (DLTs) (time frame: Approximately 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2018.