Details

Details

Title LCCC 1123: Phase II Study of Stereotactic Radiosurgery or Other Local Ablation Followed by Erlotinib for Patients with EGFR Mutation Who Have Previously Progressed on an EGFR-TKI

IRB UNC1512

CC 12-1096

Hospital Main Campus

Stage Stage 4

Phase Phase 2

Disease Lung

Drug Erlotinib

Description

Description

  1. Primary
    • To estimate PFS after locally ablative therapy and erlotinib in EGFR-mutant NSCLC patients who progressed on prior EGFR-TKI therapy
  2. Secondary
    • To evaluate local control of sites previously progressive on erlotinib following SRS followed by erlotinib
    • To estimate OS after locally ablative therapy and erlotinib in EGFR-mutant NSCLC patients who progressed on prior EGFR-TKI therapy
    • To characterize the toxicity of SRS
    • To characterize the toxicity of erlotinib when preceded by SRS
Inclusion Criteria

Inclusion Criteria

  1. Written informed consent has been obtained.
  2. ≥18 years of age
  3. Histologically or cytologically confirmed stage IV EGFR-mutant NSCLC or, in the absence of availability of EGFR testing (for example, inadequate tissue), clinical response overwhelmingly consistent with EGFR mutation (PR plus at least 6 months free of progressive disease as a consequence of EGFR-TKI therapy).
  4. History of previous response to EGFR-TKI, defined as either a PR by RECIST1.1 criteria, or at least six months without progressive disease as a result of EGFR-TKI therapy
  5. Progressive disease as measured via RECIST1.1 following EGFR-TKI therapy (with ≤5 sites of disease amenable to SRS or other locally-ablative treatment)
  6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  7. Adequate organ and marrow function as defined below:
    • Absolute neutrophil count [ANC] ≥ 1,500 cells/μL
    • Hemoglobin ≥ 10 g/dL
    • Platelets ≥ 100,000/μL
    • Serum creatinine ≤ 1.5 mg/dL or calculated creatinine clearance ≥ 60 mL/min
    • Total bilirubin ≤ 3.0 x upper limit of normal [ULN]
    • Alanine aminotransferase [ALT] ≤ 2.5 x ULN
    • Aspartate aminotransferase [AST] ≤ 2.5 x ULN
  8. Female patients must have a negative urine or serum pregnancy test at screening(pregnancy test not required for patients with bilateral oophorectomy and/or hysterectomy or for those patients who are > 1 year postmenopausal).
  9. All patients of reproductive potential must agree to use adequate contraception
Exclusion Criteria

Exclusion Criteria

  1. Any unresolved chronic toxicities > grade 2, measured by CTCAE v4.
  2. Treatment with any FDA approved or experimental cancer treatment following progression on EGFR-TKI (e.g., radiation or chemotherapy; supportive regimens such as denosumab or zoledronic acid will not result in exclusion)
  3. Any history of previous ≥ grade 3 toxicity attributable to erlotinib (except dermatological toxicity)
  4. Pregnant or lactating female
  5. Any previous radiation to sites of planned SRS. A patient may be deemed eligible in this case if a non-radiation mode of local ablation such as surgical resection is deemed safe and feasible by the PI.
  6. History of another malignancy; exception: Subjects who have been disease-free for 3 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.
  7. Concomitant anticancer therapy, immunotherapy, or radiation therapy (no radiation within prior 4 weeks).
  8. Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory, hepatic, renal, or cardiac disease)
  9. Known hypersensitivity reaction or idiosyncrasy to erlotinib
  10. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol
  11. Any other concurrent condition that in the investigator's opinion would jeopardize compliance with the protocol