Trial of Ruxolitinib and Erlotinib in Patients With EGFR-mutant Lung Adenocarcinoma With Acquired Resistance to Erlotinib

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02155465
Recruitment Status : Completed
First Posted : June 4, 2014
Last Update Posted : October 19, 2017
Incyte Corporation
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Brief Summary:
This is a phase 2 study. The goal of this study is to find out what effects, good and/or bad, taking erlotinib and ruxolitinib has on the patients and on lung cancer. Erlotinib and ruxolitinib are FDA approved for other indications, but the use of erlotinib and ruxolitinib together has not been studied before and is not FDA-approved.

Condition or disease Intervention/treatment Phase
Lung Cancer Drug: Ruxolitinib Drug: Erlotinib Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Trial of Ruxolitinib and Erlotinib in Patients With EGFR-mutant Lung Adenocarcinoma With Acquired Resistance to Erlotinib
Actual Study Start Date : June 2014
Actual Primary Completion Date : October 2017
Actual Study Completion Date : October 2017

Arm Intervention/treatment
Experimental: Ruxolitinib and Erlotinib

Phase I The study will follow a standard 3+3 dose escalation trial design. Three to six patients will need to be enrolled at each dose level and assessed for DLT for 1 full cycle (21 days) before a dose escalation decision is made.

Phase II Once the MTD has been determined, patients will be enrolled in the phase 2 portion of the single-arm, two-stage, open-label study to determine efficacy of erlotinib and ruxolitinib. Patients will receive erlotinib and ruxolitinib at the MTD established in the phase I portion. The patient take their previous dose of erlotinib if it is less than 150mg daily.

Drug: Ruxolitinib

Ruxolitinib 10mg PO BID

Ruxolitinib 15mg PO BID

Ruxolitinib 20mg PO BID

Drug: Erlotinib
Erlotinib 150mg PO QD

Primary Outcome Measures :
  1. maximally tolerated dose (MTD) (Phase I) [ Time Frame: 1 year ]
    All patients will receive erlotinib at 150mg orally daily along with doses of ruxolitinib orally twice daily. Patients in dose level 1 will receive erlotinib 150mg orally daily and ruxolitinib 10mg orally twice daily. In dose level 2, patients will receive erlotinib 150mg orally daily and ruxolitinib 15mg orally twice daily. In dose level 3, patients will receive erlotinib 150mg orally daily and ruxolitinib 20mg orally twice daily.

  2. Assess overall response rate (Phase I) [ Time Frame: 1 year ]
    Tumor response will be assessed using RECIST 1.1.

Secondary Outcome Measures :
  1. toxicity profile (Phase I) [ Time Frame: 2 years ]
    Toxicity grading will be performed in accordance with NCI CTCAE, version 4.0.

  2. survival (Phase II) [ Time Frame: 2 years ]
    Overall survival and time to progression will be estimated using the Kaplan-Meier method, with the follow-up starting at the initiation of therapy.

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Ages Eligible for Study:   19 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Pathologic evidence of advanced (non-operable or metastatic) biopsy-proven stage IV or recurrent lung cancer reviewed at MSKCC.
  • a documented somatic activating mutation in EGFR (including but not limited to Exon 19 deletion or L858R)
  • Radiographic progression during treatment with erlotinib. Prior chemotherapy regimens are permitted.
  • Received erlotinib or other EGFR TK treatment for at least 2 weeks prior to enrollment
  • Measurable (RECIST 1.1) indicator lesion not previously irradiated
  • Must have undergone biopsy after development of acquired resistance to erlotinib (which is performed as standard of care) with adequate tissue to determine EGFR T790M and tumor histology. Slides from an outside institution may be used.
  • KPS ≥ 70%
  • Age>18 years old
  • Patients must have adequate organ function:

    • AST, ALT, Alk phos ≤ 3.0 x ULN
    • Total bilirubin ≤ 2.0 x ULN
    • Creatinine <2.0 X upper limit of normal and/or a creatinine clearance ≥ 60ml/min
    • Absolute neutrophil count (ANC) ≥1,000 cells/mm³.
    • Platelet count ≥ 100,000/mm³
    • Hemoglobin ≥ 9.0g/dL.

Exclusion Criteria:

  • Concurrent therapy with a potent CYP3A4 inducer or inhibitor. Subjects may enter screening when therapy with the potent inhibitor or inducer is completed and may begin study treatment after 1 week or 5 half-lives, whichever is longer.
  • Patients with symptomatic brain metastasis requiring escalating doses of steroids.
  • Any type of systemic therapy (chemotherapy or experimental drugs) within 3 weeks of starting treatment on protocol except for erlotinib or other EGFR TKI.
  • Any radiation within 2 weeks prior to starting treatment on protocol
  • Patients with ≥ grade 2 or greater diarrhea despite maximal medical management due to medications or a medical condition such as Crohn's disease, malabsorption.
  • Inadequate recovery from any toxicities related to prior treatment (to Grade 1 or baseline).
  • Pregnant or lactating women
  • Patients who have received prior treatment with JAK inhibitor
  • Previously or current malignancies at other sites within the last 2 years, with the exception of adequately treated in situ carcinoma of the cervix, basal or squamous cell carcinoma of the skin, prostate cancer that does not require active treatment per National Comprehensive Cancer Network (NCCN) guidelines, superficial bladder cancer or other noninvasive indolent or stage 1 malignancy without sponsor approval.
  • Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months from Day 1 of study drug administration, New York Heart Association Class III or IV congestive heart failure, or symptomatic arrythmias requiring therapy,
  • Chronic or current active infections requiring systemic antibiotics, antifungals or antiviral therapy.
  • Known human immunodeficiency virus infection, or hepatitis B virus (HBV) viremia or hepatitis C virus (HCV) viremia. Screening for the study does not require assessment for these infections if not already known.
  • Any other condition that, in the opinion of the Investigator, may compromise the safety, compliance of the patient, or would preclude the patient from successful completion of the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02155465

United States, New Jersey
Memoral Sloan Kettering Cancer Center
Basking Ridge, New Jersey, United States
United States, New York
Memorial Sloan Kettering Cancer Center @ Suffolk
Commack, New York, United States, 11725
Memorial Sloan Kettering West Harrison
Harrison, New York, United States, 10604
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Memorial Sloan Kettering at Mercy Medical Center
Rockville Centre, New York, United States
Memoral Sloan Kettering Cancer Center at Phelps
Sleepy Hollow, New York, United States, 10591
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Incyte Corporation
Principal Investigator: Helena Yu, MD Memorial Sloan Kettering Cancer Center

Additional Information:
Responsible Party: Memorial Sloan Kettering Cancer Center Identifier: NCT02155465     History of Changes
Other Study ID Numbers: 14-043
First Posted: June 4, 2014    Key Record Dates
Last Update Posted: October 19, 2017
Last Verified: October 2017

Keywords provided by Memorial Sloan Kettering Cancer Center:

Additional relevant MeSH terms:
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Erlotinib Hydrochloride
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action