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Personalized Adaptive Radiation Therapy With Individualized Systemic Targeted Therapy (PARTIST) for Locally Advanced, Non-small Cell Lung Cancer With Genomic Driver Mutations

Primary Purpose

Non-Small Cell Lung Cancer

Status
Withdrawn
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
PET-Adaptive RT
Erlotinib
Crizotinib
Sponsored by
University of Michigan Rogel Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Small Cell Lung Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Michigan Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

EGFR Mutation

ALK Rearrangement

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Time to Progression From the Initiation of Study Treatment For ALK + and EGFR + Patients
Time to Death From Initiation of Study Treatment For ALK + and EGFR + Patients

Secondary Outcome Measures

The Number of Patients Experiencing Pneumonitis and Esophagitis
The Number of Patients Experiencing Grade 3 or Higher Toxicities

Full Information

First Posted
October 24, 2014
Last Updated
June 23, 2016
Sponsor
University of Michigan Rogel Cancer Center
Collaborators
Augusta University
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1. Study Identification

Unique Protocol Identification Number
NCT02277457
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2016
Overall Recruitment Status
Withdrawn
Study Start Date
September 2015 (undefined)
Primary Completion Date
June 2021 (Anticipated)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Michigan Rogel Cancer Center
Collaborators
Augusta University

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Small Cell Lung Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
EGFR Mutation
Arm Type
Experimental
Arm Description
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.
Arm Title
ALK Rearrangement
Arm Type
Experimental
Arm Description
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.
Intervention Type
Radiation
Intervention Name(s)
PET-Adaptive RT
Intervention Description
All patients will be treated with response-driven PET-adaptive RT. The radiation dose will be delivered in greater than or equal to 2.2 Gy per daily fraction to FDG-PET/CT-guided target volumes with the treatment duration limited to 30 fractions and total radiation dose limited to 66-80.4 Gy.
Intervention Type
Drug
Intervention Name(s)
Erlotinib
Intervention Description
150 mg once daily
Intervention Type
Drug
Intervention Name(s)
Crizotinib
Intervention Description
250 mg twice daily
Primary Outcome Measure Information:
Title
Time to Progression From the Initiation of Study Treatment For ALK + and EGFR + Patients
Time Frame
5 Years
Title
Time to Death From Initiation of Study Treatment For ALK + and EGFR + Patients
Time Frame
5 Years
Secondary Outcome Measure Information:
Title
The Number of Patients Experiencing Pneumonitis and Esophagitis
Time Frame
5 Years
Title
The Number of Patients Experiencing Grade 3 or Higher Toxicities
Time Frame
5 Years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gregory Kalemkerian, M.D.
Organizational Affiliation
University of Michigan Rogel Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Michigan Comprehensive Cancer Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48187
Country
United States

12. IPD Sharing Statement

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Personalized Adaptive Radiation Therapy With Individualized Systemic Targeted Therapy (PARTIST) for Locally Advanced, Non-small Cell Lung Cancer With Genomic Driver Mutations

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