Description:
Hypotheses:
Short-term - Targeted therapy with erlotinib or crizotinib plus PART (Personalized Adaptive
Radiation Therapy) will be safe and will yield favorable outcomes in patients with stage III,
EGFR (Epidermal Growth Factor Receptor) + or ALK (Anaplastic Lymphoma Kinase) + NSCLC
(Non-Small Cell Lung Cancer).
Long-term - In patients with stage III NSCLC harboring driver mutations, treatment with
relevant targeted agents plus PART will improve both local-regional and systemic tumor
control resulting in improved survival relative to standard chemoradiotherapy.
Title
- Brief Title: Personalized Adaptive Radiation Therapy With Individualized Systemic Targeted Therapy (PARTIST) for Locally Advanced, Non-small Cell Lung Cancer With Genomic Driver Mutations
- Official Title: Personalized Adaptive Radiation Therapy With Individualized Systemic Targeted Therapy (PARTIST) for Locally Advanced, Non-small Cell Lung Cancer With Genomic Driver Mutations
Clinical Trial IDs
- ORG STUDY ID:
UMCC 2014.117
- SECONDARY ID:
HUM00094166
- NCT ID:
NCT02277457
Conditions
- Non-Small Cell Lung Cancer
Interventions
| Drug | Synonyms | Arms |
|---|
| Erlotinib | | EGFR Mutation |
| Crizotinib | | ALK Rearrangement |
Purpose
Hypotheses:
Short-term - Targeted therapy with erlotinib or crizotinib plus PART (Personalized Adaptive
Radiation Therapy) will be safe and will yield favorable outcomes in patients with stage III,
EGFR (Epidermal Growth Factor Receptor) + or ALK (Anaplastic Lymphoma Kinase) + NSCLC
(Non-Small Cell Lung Cancer).
Long-term - In patients with stage III NSCLC harboring driver mutations, treatment with
relevant targeted agents plus PART will improve both local-regional and systemic tumor
control resulting in improved survival relative to standard chemoradiotherapy.
Detailed Description
The proposed trial is a pilot study that will accrue 30 patients with inoperable stage IIIA/B
NSCLC harboring either an EGFR mutation (n=20) or an ALK rearrangement (n=10). Patients with
EGFR+ tumors will be treated with erlotinib 150 mg orally QD; patients with ALK+ tumors will
be treated with crizotinib 250 mg orally BID. Treatment consists of six weeks of concurrent
PART plus erlotinib or crizotinib, followed by erlotinib or crizotinib for a total of 1 year.
All patients will be treated with response-driven PART with dose intensified to the active
(FDG-avid) region based on a mid-treatment FDG-PET/CT scan while maintaining dose limits for
organs-at-risk. The primary endpoints will be PFS and OS. Primary analyses will be performed
separately for ALK+ and EGFR+ patients. The secondary endpoint of treatment-related toxicity
will focus on pneumonitis and esophagitis with a strict stopping rule in place.
Current standard therapy affords suboptimal outcomes for patients with locally advanced NSCLC
due to both locoregional and distant recurrences. Since targeted therapy is more effective
than chemotherapy in patients with relevant driver mutations, the best way to significantly
improve outcomes in this subgroup of patients is to optimize systemic therapy with targeted
agents while improving local control with PET-adapted, high-dose RT.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| EGFR Mutation | Experimental | Patients with an identified EGFR mutation will receive PET (Positron Emission Tomography) - Adaptive RT (Radiation Therapy) plus concurrent Erlotinib followed by 1 year total of Erlotinib Treatment. | |
| ALK Rearrangement | Experimental | Patients with an identified EGFR mutation will receive PET (Positron Emission Tomography) - Adaptive RT (Radiation Therapy) plus concurrent Crizotinib followed by 1 year total ofCrizotinib Treatment. | |
Eligibility Criteria
Inclusion Criteria:
- Patients with FDG-avid (radioactive glucose) and pathologically proven stage IIA-IIB
or IIIA-IIIB non-small cell lung cancer (according to AJCC [American Joint Committee
on Cancer] staging, 7th edition).
- Patients with tumors that harbor either EGFR sensitizing mutations or ALK
rearrangement.
- Patients must be considered unresectable or medically inoperable; patients who decline
surgery are also eligible.
- Patients must be 18 years of age or older.
- Patients with ECOG (Eastern Cooperative Oncology Group) performance status of 0-2.
- Patients must have adequate organ function.
- Patients must be able to take oral medications.
- Women with reproductive capability must be willing to use effective contraception.
- Patients must be informed of the investigational nature of this study and sign written
informed consent in accordance with institutional and federal guidelines.
- Patients must be willing to comply with study procedures.
Exclusion Criteria:
- Patients with tumors that have a component of small cell carcinoma.
- Patients wtih stage I, II, or IV disease, including malignant pleural or pericardial
effusion.
- Prior radiotherapy to the thorax such that composite radiation would significantly
over-dose critical structures, either per estimation of the treating radiation
oncologist or defined by failure to meet normal tissue tolerance constraints.
- Patients who cannot tolerate thoracic radiotherapy or targeted therapy.
- Patients wtih a prior diagnosis of interstitial lung disease or pulmonary fibrosis.
- Patients who cannot take oral medication, require intravenous alimentation, had prior
surgical procedures affecting gastrointestinal absorption, or have active peptic ulcer
disease.
- Hypersensitivity to erlotinib, crizotinib, or to any of the excipients.
- Pregnant women are excluded from this study because radiation has the potential for
teratogenic or abortifacient effects.
- Prisoners are excluded from this study.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Time to Progression From the Initiation of Study Treatment For ALK + and EGFR + Patients |
| Time Frame: | 5 Years |
| Safety Issue: | |
| Description: | |
Secondary Outcome Measures
| Measure: | The Number of Patients Experiencing Pneumonitis and Esophagitis |
| Time Frame: | 5 Years |
| Safety Issue: | |
| Description: | |
| Measure: | The Number of Patients Experiencing Grade 3 or Higher Toxicities |
| Time Frame: | 5 Years |
| Safety Issue: | |
| Description: | |
Details
| Phase: | Early Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Withdrawn |
| Lead Sponsor: | University of Michigan Rogel Cancer Center |
Last Updated
June 24, 2016
