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A Randomized Phase II Study of Individualized Combined Modality Therapy for Stage III Non-Small Cell Lung Cancer (NSCLC)


Phase 2
18 Years
N/A
Not Enrolling
Both
Stage IIIA Non-small Cell Lung Cancer, Stage IIIB Non-small Cell Lung Cancer

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Trial Information

A Randomized Phase II Study of Individualized Combined Modality Therapy for Stage III Non-Small Cell Lung Cancer (NSCLC)


PRIMARY OBJECTIVES:

I. To assess whether patients with unresectable local-regionally advanced non-small cell
lung cancer (NSCLC) treated with targeted agents based on molecular characteristics have a
longer progression-free survival than those treated with standard care therapy alone.

SECONDARY OBJECTIVES:

I. To evaluate response rate. II. To assess toxicity. III. To assess overall survival. IV.
To correlate clinical outcomes with tumor molecular aberrations identified from deep
sequencing of selected kinomes in patients from whom adequate baseline tissue is available.

OUTLINE: Patients are randomized to 1 of 4 treatment arms. Patients are stratified according
to mutation status.

CHEMORADIATION: In all treatment arms, patients undergo concurrent intensity modulated
radiation therapy (IMRT) or 3-dimensional conformal radiation therapy (3-D CRT) once daily
(QD) 5 days a week for 6 weeks. Patients receive 1 of 2 chemotherapy regimens based on the
discretion of the treating physician. Patients receive cisplatin intravenously (IV) over 1-2
hours on days 1, 8, 29, and 36 and etoposide IV over 1 hour on days 1-5 and 29-33. Treatment
repeats every 4 weeks for up to 2 courses in the absence of disease progression or
unacceptable toxicity. Some patients receive paclitaxel IV on days 1, 8, 15, 22, 29, and 36
and carboplatin IV weekly during radiation therapy for 6 weeks. Two courses of consolidation
treatment will begin 4-6 weeks after completion of radiation therapy with paclitaxel IV on
days 1 and 22 and carboplatin IV on days 1 and 22 in the absence of disease progression or
unacceptable toxicity.

ARM I (induction therapy): Patients receive erlotinib hydrochloride orally (PO) QD for up to
12 weeks. Patients achieving disease progression after 6 weeks undergo concurrent
chemoradiation therapy.

ARM III (induction therapy): Patients receive crizotinib PO twice daily (BID) for up to 12
weeks. Patients achieving disease progression after 6 weeks undergo concurrent
chemoradiation therapy.

ARMS II AND IV (concurrent chemoradiation): Patients receive concurrent chemotherapy with
thoracic radiation therapy beginning on day 1. Treatment continues in the absence of disease
progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 1 month, every 3 months for
2 years, every 6 months for 3 years and then yearly thereafter.


Inclusion Criteria:



- Histologically or cytologically confirmed, newly diagnosed non-squamous NSCLC

- Unresectable stage IIIA or IIIB disease; patients must be surgically staged to
confirm N2 or N3 disease; patients may have invasive mediastinal staging by
mediastinoscopy, mediastinotomy, EBUS-TBNA, EUS, or VATS within 30 days prior to
registration

- Patients with any T with N2 or N3 are eligible; patients with T3, N1-N3 disease are
eligible if deemed unresectable; patients with T4, any N are eligible

- Patients must have measurable disease, i.e., lesions that can be accurately measured
in at least 1 dimension (longest dimension in the plane of measurement is to be
recorded) with a minimum size of 10 mm by CT scan (CT scan slice thickness no greater
than 5 mm); tumor measurements must be taken within 42 days prior to registration

- Patients with a pleural effusion, which is a transudate, cytologically negative and
non-bloody, are eligible if the radiation oncologist feels the tumor can be
encompassed within a reasonable field of radiotherapy

- If a pleural effusion can be seen on the chest CT but not on chest x-ray and is too
small to tap, the patient will be eligible; patients who develop a new pleural
effusion after thoracotomy or other invasive thoracic procedure will be eligible

- The institution's pre-enrollment biomarker screening at a CLIA certified lab
documents presence of known "sensitive" mutations in EGFR TK domain (exon 19
deletion, L858) and EML4-ALK fusion arrangement; either the primary tumor or the
metastatic lymph node tissue may be used for testing of mutations

- The institution's pre-enrollment biomarker screening at a CLIA certified lab
documents absence of T790M mutation in the EGFR TK domain

- Appropriate stage for protocol entry, including no distant metastases, based upon the
following minimum diagnostic workup:

- History/physical examination, including recording of pulse, blood pressure (BP),
weight, and body surface area, within 45 days prior to registration

- Whole body fludeoxyglucose-positron emission tomography (FDG-PET)/CT (orbits to
mid-thighs) within 30 days prior to registration; PET/CT must be negative for
distant metastasis

- CT scan of the chest with contrast (unless medically contraindicated) within 30
days prior to registration;

- Magnetic resonance imaging (MRI) of the brain with contrast (or CT scan with
contrast, if MRI medically contraindicated) within 30 days prior to registration

- Zubrod performance status 0-1 within 14 days prior to registration

- Absolute neutrophil count (ANC) >= 1,500 cells/mm^3

- Platelets >= 100,000 cells/mm^3

- Hemoglobin >= 8.0 g/dl (Note: the use of transfusion or other intervention to achieve
hemoglobin [Hgb] >= 8.0 g/dl is acceptable)

- Calculated creatinine clearance >= 50 ml/min (by Cockroft-Gault formula) within 14
days prior to registration

- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 3 X upper limit of
normal (ULN) within 14 days prior to registration

- Bilirubin < 3 X ULN within 14 days prior to registration

- Negative serum pregnancy test within 14 days prior to registration for women of
childbearing potential

- Patient must provide study specific informed consent prior to study entry, including
consent for mandatory screening of tissue

Exclusion Criteria:

- Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free
for a minimum of 730 days (2 years) (for example, carcinoma in situ of the breast,
oral cavity, or cervix are all permissible)

- Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a
different cancer is allowable

- Prior radiotherapy to the region of the study cancer that would result in overlap of
radiation therapy fields

- Atelectasis of the entire lung

- Contralateral hilar node involvement

- Exudative, bloody, or cytologically malignant effusions

- Severe, active co-morbidity, defined as follows:

- Unstable angina and/or congestive heart failure requiring hospitalization within
the last 6 months

- Transmural myocardial infarction within the last 6 months

- Acute bacterial or fungal infection requiring intravenous antibiotics at the
time of registration

- Chronic obstructive pulmonary disease exacerbation or other respiratory illness
requiring hospitalization or precluding study therapy at the time of
registration; hepatic insufficiency resulting in clinical jaundice and/or
coagulation defects; note, however, that laboratory tests for liver function and
coagulation parameters are not required for entry into this protocol

- Acquired immune deficiency syndrome (AIDS) based upon current Centers for
Disease and Control (CDC) definition; note, however, that human immunodeficiency
virus (HIV) testing is not required for entry into this protocol; the need to
exclude patients with AIDS from this protocol is necessary because the
treatments involved in this protocol may be significantly immunosuppressive;
protocol-specific requirements may also exclude immuno-compromised patients

- Pregnancy or women of childbearing potential and men who are sexually active and not
willing/able to use medically acceptable forms of contraception; this exclusion is
necessary because the treatment involved in this study may be significantly
teratogenic

- Prior allergic reaction to the study drug(s) involved in this protocol

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival (PFS)

Outcome Description:

The product limit estimator developed by Kaplan and Meier will be used. Their 95% confidence intervals will be estimated. Comparisons between arms will be conducted using a log rank test.

Outcome Time Frame:

Occurrence of local or regional progression, distant metastases, or death from any cause from the time of randomization to the occurrence of one of the failure events, whichever occurs first, assessed up to 12 months

Safety Issue:

No

Principal Investigator

Ramaswamy Govindan

Investigator Role:

Principal Investigator

Investigator Affiliation:

Radiation Therapy Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2013-00737

NCT ID:

NCT01822496

Start Date:

April 2013

Completion Date:

Related Keywords:

  • Stage IIIA Non-Small Cell Lung Cancer
  • Stage IIIB Non-Small Cell Lung Cancer
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms

Name

Location

Radiation Therapy Oncology GroupPhiladelphia, Pennsylvania  19107