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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Collaborator:
Incyte Corporation
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT02155465
First received: June 2, 2014
Last updated: June 3, 2014
Last verified: June 2014
  Purpose

This is a phase 1 study. The goal of this study is to test the safety of combining the drugs erlotinib and ruxolitinib at different dose levels. The investigators want 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 Intervention Phase
Lung Cancer
Drug: Ruxolitinib
Drug: Erlotinib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • maximally tolerated dose (MTD) (Phase I) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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.

  • Assess overall response rate (Phase I) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Tumor response will be assessed using RECIST 1.1.


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

  • survival (Phase II) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Overall survival and time to progression will be estimated using the Kaplan-Meier method, with the follow-up starting at the initiation of therapy.


Estimated Enrollment: 43
Study Start Date: June 2014
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Drug: Ruxolitinib

Ruxolitinib 10mg PO BID

Ruxolitinib 15mg PO BID

Ruxolitinib 20mg PO BID

Drug: Erlotinib
Erlotinib 150mg PO QD

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 by RECIST 1.1 during treatment with erlotinib. Prior chemotherapy regimens are permitted.
  • Received erlotinib treatment for at least 1 month 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02155465

Contacts
Contact: Helena Yu, MD 646-888-4274
Contact: Gregory Riely, MD, PhD 646-888-4199

Locations
United States, New Jersey
Memoral Sloan Kettering Cancer Center Recruiting
Basking Ridge, New Jersey, United States
Contact: Helena Yu, MD    646-888-4274      
United States, New York
Memorial Sloan Kettering Cancer Center @ Suffolk Recruiting
Commack, New York, United States, 11725
Contact: Helena Yu, MD    646-888-4274      
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Helena Yu, MD    646-888-4274      
Contact: Gregory Riely, MD, PhD    646-888-4199      
Principal Investigator: Helena Yu, MD         
Memorial Sloan Kettering at Mercy Medical Center Recruiting
Rockville Centre, New York, United States
Contact: Helena Yu, MD    646-888-4274      
Memoral Sloan Kettering Cancer Center at Phelps Recruiting
Sleepy Hollow, New York, United States, 10591
Contact: Helena Yu, MD    646-888-4274      
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Incyte Corporation
Investigators
Principal Investigator: Helena Yu, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT02155465     History of Changes
Other Study ID Numbers: 14-043
Study First Received: June 2, 2014
Last Updated: June 3, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
Ruxolitinib
Erlotinib
EGFR-mutant
14-043

Additional relevant MeSH terms:
Adenocarcinoma
Lung Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Erlotinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014