Local Therapies for Oligometastatic Non-Small Cell Lung Cancer Harboring Sensitizing EGFR Mutations

Pilot Study of Local Therapies for Oligometastatic Non-Small Cell Lung Cancer Harboring Sensitizing EGFR Mutations

This study will test if local therapies in addition to erlotinib can improve responses and delay the time until new treatment is required. This study will also collect blood samples for research blood tests.

Study Overview

• Status: Completed
• Conditions: Oligometastatic Lung Adenocarcinoma
• Intervention / Treatment: Drug: Erlotinib; Other: Local Therapies

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Basking Ridge, New Jersey, United States
      • Memoral Sloan Kettering Cancer Center
    • Middletown, New Jersey, United States, 07748
      • Memorial Sloan Kettering Monmouth
  • New York
    • Commack, New York, United States, 11725
      • Memorial Sloan Kettering Cancer Center @ Suffolk
    • Harrison, New York, United States, 10604
      • Memorial Sloan Kettering Westchester
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • Rockville Centre, New York, United States
      • Memorial Sloan Kettering at Mercy Medical Center
    • Sleepy Hollow, New York, United States, 10591
      • Memoral Sloan Kettering Cancer Center at Phelps

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Newly diagnosed metastatic lung adenocarcinoma (recurrent or de novo) harboring sensitizing EGFR mutations (L858R, exon 19 deletion, G719A, L861Q, S768I, exon 19 insertions) with oligometastatic disease (≤5 discrete lesions of disease irrespective of location, inclusive of the primary lesion):
• all sites of disease must be amenable to definitive treatment with a local therapy (surgical resection, stereotactic radiosurgery, ablation and conventional radiation therapy) as determined by surgery, interventional radiology and radiation oncology
• all intrathoracic lymph nodes (including hilar, mediastinal, and supraclavicular nodal disease) are considered 1 discrete lesion.
• Each brain metastasis is included as a distinct lesion.
• Patients already started on erlotinib are eligible as long as their sites of disease are determined to be eligible for definitive local therapy by consensus of the principal investigators within 12 weeks of the patient first taking erlotinib.
• Lung adenocarcinoma histology confirmed at MSKCC.
• Available archived tissue to perform molecular analysis
• Patients without available archived tissue can have repeat biopsies to determine EGFR status as per standard clinical care guidelines
• Age 18 years or older
• Karnofsky Performance Status ≥ 70%
• Adequate bone marrow, liver and renal function, as specified below:
• Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L
• Hemoglobin ≥ 8 g/dL
• Platelets ≥ 100 x 109/L
• Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN) (except for patients with documented Gilbert's Syndrome)
• AST and ALT ≤ 2.5 x ULN or ≤ 5 x ULN if liver metastases are present
• Serum creatinine ≤ 1.5 x upper limit of normal or creatinine clearance ≥ 60ml/min for patients with creatinine levels above institutional normal.
• For women of child-bearing potential, negative pregnancy test within 14 days prior to starting treatment
• Men and women of childbearing age must be willing to use effective contraception while on treatment and for at least 3 months thereafter

Exclusion Criteria:

• Treatment with erlotinib prior to developing metastatic disease
• Patients with activating but not sensitizing mutations (exon 20 insertions, EGFR T790M)
• Malignant pleural effusion or pleural disease
• Leptomeningeal disease
• Any site of disease that is not amenable to definitively local therapy including surgery or radiation therapy
• Women who are breastfeeding or pregnant
• Concurrent malignancies other than non-melanoma skin cancer that require active ongoing treatment.
• Any medical co-morbidities that would preclude surgery or radiation therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Oligometastatic Non-Small Cell Lung Cancer; Patients will be placed on EGFR-TKI for their metastatic EGFR-mutant stage IV oligometastatic disease. All patients will undergo induction TKI for 12 weeks. At the conclusion of 12 weeks on erlotinib, patients without disease progression [partial response (PR) or stable disease (SD)] will undergo definitive local treatment to all remaining sites of disease. After local therapy, erlotinib will be resumed until progression of disease (POD) by RECIST criteria. All assessments completed during the 12 week TKI induction phase are to be performed per protocol with a ± 7 day window.

Drug: Erlotinib; Other: Local Therapies; Definitive local therapies include surgical resection, stereotactic radiosurgery, ablation and conventional radiation therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility as Measured by at Least Five Patients Will Need to Complete Local Therapy.	At least five patients will need to complete local therapy within 2 years of the study being open to accrual for the primary endpoint to be met.	2 years

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2015
• Primary Completion (Actual): December 11, 2017
• Study Completion (Actual): December 11, 2017

Study Registration Dates

• First Submitted: May 14, 2015
• First Submitted That Met QC Criteria: May 18, 2015
• First Posted (Estimate): May 21, 2015

Study Record Updates

• Last Update Posted (Actual): May 21, 2018
• Last Update Submitted That Met QC Criteria: April 20, 2018
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: Surgery; Erlotinib; Radiation Therapy; Sensitizing EGFR Mutations; 15-067
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Adenocarcinoma of Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Erlotinib Hydrochloride
• Other Study ID Numbers: 15-067

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No