Clinical Trials /

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

NCT02277457

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Withdrawn

Phase:

Early Phase 1

Trial Eligibility

Document

Personalized Adaptive <span class="go-doc-concept go-doc-intervention">Radiation</span> Therapy With Individualized Systemic <span class="go-doc-concept go-doc-intervention">Targeted Therapy</span> (PARTIST) for Locally Advanced, Non-small Cell <span class="go-doc-concept go-doc-disease">Lung Cancer</span> With Genomic Driver <span class="go-doc-concept go-doc-keyword">Mutations</span>

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

    NCT ID: NCT02277457

    ORG ID: UMCC 2014.117

    NCI ID: HUM00094166

    Trial Conditions

    Non-Small Cell Lung Cancer

    Trial Interventions

    Drug Synonyms Arms
    Erlotinib EGFR Mutation
    Crizotinib ALK Rearrangement

    Trial 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. Erlotinib
    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. Crizotinib

    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.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    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

    Trial Keywords