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

NCT02155465 | Completed Phase 1 Results

• 1 other identifier: 14-043
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 6

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.

Conditions

Lung Cancer

Keywords

Ruxolitinib; Erlotinib; EGFR-mutant; 14-043

Outcome Measures

Primary Outcomes (2)

• Maximally Tolerated Dose (MTD) (Phase I)

  1 year

• Assess Overall Response Rate

  Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), at least a 30% decrease in the sum of the longest diameter of target lesions; Progressive disease (PD), at least a 20% increase in the sum of the diameter of the target lesions or the appearance of one or more new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD

  1 year

Secondary Outcomes (2)

• Number of Participants With NCI CTCAE Toxicity

  2 years

• Progression-free Survival

  2 years

Study Arms (1)

Ruxolitinib and Erlotinib

EXPERIMENTAL

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; Drug: Erlotinib

Interventions

Ruxolitinib DRUG

Ruxolitinib 10mg PO BID Ruxolitinib 15mg PO BID Ruxolitinib 20mg PO BID

Ruxolitinib and Erlotinib

Erlotinib DRUG

Erlotinib 150mg PO QD

Ruxolitinib and Erlotinib

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Incyte Corporation: collaborator

Study Sites (6)

Memoral Sloan Kettering Cancer Center

Basking Ridge, New Jersey, United States

Location

Memorial Sloan Kettering Cancer Center @ Suffolk

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering West Harrison

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering at Mercy Medical Center

Rockville Centre, New York, United States

Location

Memoral Sloan Kettering Cancer Center at Phelps

Sleepy Hollow, New York, 10591, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Lung Neoplasms

Interventions

ruxolitinib; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Helena Yu, MD
• Organization: Memorial Sloan Kettering Cancer Center

YuH@mskcc.org

646-888-4274

Study Officials

• Helena Yu, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: June 2, 2014
• First Posted: June 4, 2014
• Study Start: June 1, 2014
• Primary Completion: October 1, 2017
• Study Completion: October 1, 2017
• Last Updated: January 16, 2019
• Results First Posted: January 3, 2019

Record last verified: 2017-10

Locations

US (6)