Lung Cancer
Conditions
Keywords
Ruxolitinib, Erlotinib, EGFR-mutant, 14-043
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.
Interventions
DRUGErlotinib
Erlotinib 150mg PO QD
DRUGRuxolitinib
Ruxolitinib 10mg PO BID Ruxolitinib 15mg PO BID Ruxolitinib 20mg PO BID
Sponsors
Incyte Corporation
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximally Tolerated Dose (MTD) (Phase I) | 1 year | — |
| Assess Overall Response Rate | 1 year | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With NCI CTCAE Toxicity | 2 years | Toxicity grading will be performed in accordance with NCI CTCAE, version 4.0. |
| Progression-free Survival | 2 years | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Phase 1: Level 1 Level 1 (10mg Ruxolitinib PO bid/ 150mg PO qd Erlotinib) | 3 |
| Phase 1: Level 2 Level 2 (15mg Ruxolitinib PO bid/ 150mg PO qd Erlotinib) | 3 |
| Phase 1: Level 3 Level 3 (20mg Ruxolitinib PO bid/ 150mg PO qd Erlotinib) | 6 |
| Phase 2: 20mg Ruxolitinib PO BID/ 75 mg Erlotinib PO QD 20mg Ruxolitinib PO BID/ 75 mg Erlotinib PO QD | 2 |
| PHASE 2: 20mg Ruxolitinib PO BID / 50 mg Erlotinib PO qd 20mg Ruxolitinib PO BID / 50 mg Erlotinib PO qd | 1 |
| PHASE 2 MTD: 20mg Ruxolitinib PO BID / 150 mg Erlotinib PO qd 20mg Ruxolitinib PO BID / 150 mg Erlotinib PO qd | 2 |
| PHASE 2 MTD: 20mg Ruxolitinib PO BID / 100 mg Erlotinib PO qd 20mg Ruxolitinib PO BID / 100 mg Erlotinib PO qd | 5 |
| Total | 22 |
Baseline characteristics
| Characteristic | Phase 1: Level 1 | Phase 1: Level 2 | Phase 1: Level 3 | Phase 2: 20mg Ruxolitinib PO BID/ 75 mg Erlotinib PO QD | PHASE 2: 20mg Ruxolitinib PO BID / 50 mg Erlotinib PO qd | PHASE 2 MTD: 20mg Ruxolitinib PO BID / 150 mg Erlotinib PO qd | PHASE 2 MTD: 20mg Ruxolitinib PO BID / 100 mg Erlotinib PO qd | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 10 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 1 Participants | 5 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants | 12 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 2 Participants | 2 Participants | 5 Participants | 1 Participants | 1 Participants | 2 Participants | 4 Participants | 17 Participants |
| Region of Enrollment United States | 3 Participants | 3 Participants | 6 Participants | 2 Participants | 1 Participants | 2 Participants | 5 Participants | 22 Participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 4 Participants | 1 Participants | 1 Participants | 0 Participants | 4 Participants | 13 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 0 Participants | 2 Participants | 1 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 3 | 1 / 3 | 5 / 6 | 2 / 2 | 1 / 1 | 1 / 2 | 3 / 5 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 5 / 6 | 2 / 2 | 1 / 1 | 2 / 2 | 5 / 5 |
| serious Total, serious adverse events | 2 / 3 | 2 / 3 | 2 / 6 | 0 / 2 | 1 / 1 | 0 / 2 | 1 / 5 |
Outcome results
Primary
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
Time frame: 1 year
Population: Participants response to study treatment were combined and evaluated to determine an overall response rate.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase I Participants | Assess Overall Response Rate | 5 % of participants with partial response |
Primary
Maximally Tolerated Dose (MTD) (Phase I)
Time frame: 1 year
Population: Maximally Tolerated Dose (MTD) is determined by evaluating all Phase I participants as a whole. All Phase I participants are evaluated together to determine the MTD.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase I Participants | Maximally Tolerated Dose (MTD) (Phase I) | Erlotinib Daily | 150 mg |
| Phase I Participants | Maximally Tolerated Dose (MTD) (Phase I) | Ruxolitinib Twice Daily | 20 mg |
Secondary
Number of Participants With NCI CTCAE Toxicity
Toxicity grading will be performed in accordance with NCI CTCAE, version 4.0.
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase I Participants | Number of Participants With NCI CTCAE Toxicity | 3 Participants |
| Phase II Participants | Number of Participants With NCI CTCAE Toxicity | 3 Participants |
| Phase 1: Level 3 | Number of Participants With NCI CTCAE Toxicity | 6 Participants |
| Phase 2: 20mg Ruxolitinib PO BID/ 75 mg Erlotinib PO QD | Number of Participants With NCI CTCAE Toxicity | 2 Participants |
| Phase 2: 20mg Ruxolitinib PO BID / 50 mg Erlotinib PO qd | Number of Participants With NCI CTCAE Toxicity | 1 Participants |
| PHASE 2 MTD: 20mg Ruxolitinib PO BID / 150 mg Erlotinib PO qd | Number of Participants With NCI CTCAE Toxicity | 2 Participants |
| PHASE 2 MTD: 20mg Ruxolitinib PO BID / 100 mg Erlotinib PO qd | Number of Participants With NCI CTCAE Toxicity | 5 Participants |
Secondary
Progression-free Survival
Time frame: 2 years
Population: Participants response to study treatment were combined and evaluated to determine an overall progression-free survival.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase I Participants | Progression-free Survival | 2.2 months |