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A Pilot Trial of Cisplatin/Etoposide/Radiotherapy Followed by Consolidation Docetaxel and the Addition of Bevacizumab (NSC-704865) in Three Cohorts of Patients With Inoperable Locally Advanced Stage III Non-Small Cell Lung Cancer


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Both
Adenocarcinoma of the Lung, Adenosquamous Cell Lung Cancer, Bronchoalveolar Cell Lung Cancer, Large Cell Lung Cancer, Squamous Cell Lung Cancer, Stage IIIA Non-small Cell Lung Cancer, Stage IIIB Non-small Cell Lung Cancer

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Trial Information

A Pilot Trial of Cisplatin/Etoposide/Radiotherapy Followed by Consolidation Docetaxel and the Addition of Bevacizumab (NSC-704865) in Three Cohorts of Patients With Inoperable Locally Advanced Stage III Non-Small Cell Lung Cancer


PRIMARY OBJECTIVES:

I. Determine the frequency and severity of toxic effects of induction therapy comprising
cisplatin, etoposide, and radiotherapy with or without bevacizumab followed by consolidation
therapy comprising docetaxel and bevacizumab, in terms of grade 4 or 5 hemorrhage, in
patients with newly diagnosed, unresectable, stage III non-small cell lung cancer.

SECONDARY OBJECTIVES:

I. Determine progression-free and overall survival of patients treated with these regimens.

II. Determine response (confirmed, unconfirmed, partial, and complete) in patients with
measurable disease treated with these regimens.

OUTLINE: This is a pilot, multicenter study. Patients are stratified according to risk
(high* vs low).

NOTE: *High-risk stratum closed to accrual as of 2/20/09.

INDUCTION THERAPY: Patients in each stratum are assigned to 1 of 3 sequential treatment
groups.

GROUP 1: Patients receive cisplatin IV over 1 hour on days 1, 8, 29, and 36 and etoposide IV
over 1 hour on days 1-5 and 29-33. Patients undergo concurrent thoracic radiotherapy once
daily on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47.

GROUP 2: Patients receive cisplatin, etoposide, and thoracic radiotherapy as in group 1.
Patients also receive bevacizumab IV over 30-90 minutes on days 15, 36, and 57.

GROUP 3: Patients receive cisplatin, etoposide, and thoracic radiotherapy as in group 1.
Patients also receive bevacizumab IV over 30-90 minutes on days 1, 22, and 43.

CONSOLIDATION CHEMOTHERAPY: Beginning 3-6 weeks after completion of induction therapy, all
patients receive consolidation chemotherapy comprising docetaxel IV over 1 hour and
bevacizumab IV over 30-90 minutes on day 1. Patients also receive filgrastim (G-CSF)
subcutaneously (SC) beginning on day 2 and continuing until blood counts recover OR
pegfilgrastim SC once on day 2.

Treatment repeats every 21 days for 3 courses in the absence of disease progression or
unacceptable toxicity. After completion of study treatment, patients are followed
periodically for up to 4 years.


Inclusion Criteria:



- Histologically or cytologically confirmed single, primary, bronchogenic, non-small
cell lung cancer (NSCLC)

- Newly diagnosed disease

- Unresectable disease

- No more than 1 parenchymal lesions on same or opposite sides of the lungs

- Meets 1 of the following stage criteria:

- Stage IIIA (N2) disease meeting the following criteria:

- N2 mediastinal lymph nodes must be multiple and/or bulky on CT scan or
x-ray so that the patient is not a candidate for induction chemotherapy or
chemoradiotherapy followed by surgical resection

- N2 status must be documented by ≥ 1 of the following methods:

- Histologically or cytologically confirmed N2 disease by exploratory
thoracotomy, thoracoscopy, mediastinoscopy, mediastinotomy,
Chamberlain procedure, Wang needle biopsy (WNB), fine needle
aspiration (FNA) under bronchoscopic or CT guidance, or any other
method

- Node positive by fludeoxyglucose-positron emission tomography
(FDG-PET) scan

- Nodes > 3 cm on CT scan

- Paralyzed left true vocal cord with separate left lung primary
distinct from anterior-posterior window nodes on CT scan

- Stage IIIB disease meeting ≥ 1 of the following criteria:

- Histologically or radiographically confirmed positive N3 nodes*, documented
by ≥ 1 of the following methods:

- FNA, core needle biopsy (CNB), or excisional biopsy of supraclavicular
N3 nodes

- Biopsy of contralateral mediastinal N3 nodes by mediastinoscopy,
mediastinotomy, or thoracotomy

- FNA, CNB, or WNB under CT or bronchoscopic fluoroscopic guidance of
enlarged contralateral N3 mediastinal nodes

- Contralateral mediastinal nodes > 3 cm on CT scan

- Node positivity by FDG-PET scan

- Right-sided primary with paralyzed left true vocal cord

- T4 lesions of any size that invade the mediastinum, heart, great vessels,
trachea, esophagus, vertebral body, or carina, documented by ≥ 1 of the
following methods:

- Written documentation of type of T4 extent if patient had a prior
exploratory thoracotomy or thoracoscopy

- T4 involvement of the trachea or carina by direct bronchoscopic
visualization

- T4 involvement of the heart, esophagus, aorta, or vertebral body by CT
scan, MRI, or transesophageal ultrasound

- T4 involvement of the mediastinum by CT scan or MRI if, in the absence
of the above organ involvement, there is soft tissue extension
directly into the mediastinal space**

- Meets 1 of the following risk criteria:

- Low risk disease, meeting the following criteria:

- Non-squamous cell NSCLC, including adenocarcinoma, bronchoalveolar cell
carcinoma, or large cell carcinoma

- If mixed histology, the squamous cell carcinoma component must be <
50%

- Histology or cytology from involved mediastinal or supraclavicular
lymph nodes allowed if a separate distal primary lesion is clearly
evident on radiographs (i.e., second biopsy not required)

- No primary tumor with cavitation and/or tumor within 1 cm of a major vessel

- No hemoptysis (i.e., bright red blood ≥ ½ teaspoon) in the past 28 days

- High-risk* disease, meeting ≥ 1 of the following criteria:

- Squamous cell NSCLC

- If mixed histology, the squamous cell component must be ≥ 50%

- Tumor with any histology that has cavitation or is located within 1 cm of a
major vessel

- No aortic involvement

- Any histology and hemoptysis (i.e., bright red blood ≥ ½ teaspoon) within
past 28 days

- Measurable or nonmeasurable disease by CT scan or MRI

- Pleural effusions, ascites, and laboratory parameters are not acceptable as the
only evidence of disease

- No pleural effusion except for small pleural effusion visible on CT scan or MRI alone

- No pericardial effusions

- No metastatic disease involving the contralateral chest, liver, or adrenals confirmed
by CT scan of the upper abdomen or by chest CT scan with complete liver and adrenals
in the report

- Patients must be offered participation in SWOG-S9925 (Lung Cancer Specimen Repository
Protocol)

- No brain metastases by CT scan or MRI

- No evidence of cavitation

- Creatinine normal

- Creatinine clearance ≥ 50 mL/min

- FEV_1 ≥ 2.0 liters OR predicted FEV_1 of the contralateral lung > 800 mL

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Urine protein: creatinine ratio ≤ 0.5 by urinalysis OR urine protein < 1,000 mg by
24-hour urine collection

- INR < 1.5

- Zubrod performance status 0-1

- No sensory neuropathy > grade 1

- No cerebrovascular accident within the past 6 months

- No myocardial infarction or unstable angina within the past 6 months

- No uncontrolled hypertension

- No New York Heart Association class II-IV congestive heart failure

- No serious cardiac arrhythmia requiring medication

- No clinically significant peripheral vascular disease

- No evidence of bleeding diathesis or coagulopathy

- No pathologic condition other than lung cancer that carries a high risk of bleeding

- No known hypersensitivity to Chinese hamster ovary cell products or other recombinant
human antibodies

- No serious, nonhealing wound, ulcer, or bone fracture

- No other prior malignancy except adequately treated basal cell or squamous cell skin
cancer, in situ cervical cancer, adequately treated stage I or II cancer for which
the patient is currently in complete remission, or other cancer for which the patient
has been disease-free for 5 years

- Not pregnant or nursing

- No nursing during and for ≥ 6 months after the last dose of bevacizumab

- Negative pregnancy test

- Fertile patients must use effective contraception during and for ≥ 6 months after the
last dose of bevacizumab

- Must have pre-treatment simulation demonstrating a V20 ≤ 35% with planned radiation
dose of 6,480 cGy

- No prior surgical resection

- Prior exploratory thoracotomy, mediastinoscopy, excisional biopsy, or similar
surgery allowed for diagnosing, staging, or determining potential resectability
of lung tumor

- No prior chemotherapy or radiotherapy for lung cancer

- No prior radiotherapy to the neck or thorax

- At least 4 weeks since prior thoracic or other major surgery (excluding
mediastinoscopy) and recovered

- More than 7 days since prior FNA, CNB, or mediastinoscopy

- No other concurrent anticancer therapy, including chemotherapy, radiotherapy, or
biologic agents

- No other concurrent investigational drugs

- No concurrent major surgical procedures

- No concurrent full-dose anticoagulants (e.g., low-molecular weight and unfractionated
heparin or warfarin)

- Low-dose warfarin (i.e., 1 mg) is allowed to prevent clotting of an infusaport
or central line

- No concurrent brachytherapy, radiopharmaceuticals, high linear energy transfer
radiation (i.e., fast neutrons), particle therapy (i.e., protons, carbon, or helium),
and/or altered fractionation schemes

- No concurrent intensity-modulated radiotherapy

- No concurrent prophylactic contralateral hilar or supraclavicular lymph node
radiotherapy

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Incidence of grade 4 or higher hemorrhage

Outcome Time Frame:

Up to 1 year

Safety Issue:

Yes

Principal Investigator

Antoinette Wozniak

Investigator Role:

Principal Investigator

Investigator Affiliation:

Southwest Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-01097

NCT ID:

NCT00334815

Start Date:

June 2006

Completion Date:

Related Keywords:

  • Adenocarcinoma of the Lung
  • Adenosquamous Cell Lung Cancer
  • Bronchoalveolar Cell Lung Cancer
  • Large Cell Lung Cancer
  • Squamous Cell Lung Cancer
  • Stage IIIA Non-Small Cell Lung Cancer
  • Stage IIIB Non-Small Cell Lung Cancer
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Adenocarcinoma, Bronchiolo-Alveolar
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms

Name

Location

University of Mississippi Medical CenterJackson, Mississippi  39216-4505
University of Texas Health Science Center at San AntonioSan Antonio, Texas  78284-7811
Loyola University Medical CenterMaywood, Illinois  60153
University of Arkansas for Medical SciencesLittle Rock, Arkansas  72205
Salina Regional Health CenterSalina, Kansas  67401
Danville Regional Medical CenterDanville, Virginia  24541
Denver Health Medical CenterDenver, Colorado  80204-4507
Presbyterian HospitalCharlotte, North Carolina  28233-3549
Providence HospitalMobile, Alabama  36608
Tahoe Forest Cancer CenterTruckee, California  96161
University of RochesterRochester, New York  14642
Wayne State UniversityDetroit, Michigan  48202
Valley View Hospital Cancer CenterGlenwood Springs, Colorado  81601
Hays Medical CenterHays, Kansas  67601
Highlands Oncology Group-BentonvilleBentonville, Arkansas  72712
Northbay Cancer CenterFairfield, California  94533
Fremont - Rideout Cancer CenterMarysville, California  95901
Cancer Centers of Central Florida PALeesburg, Florida  34788
Saint Francis Hospital and Medical Center - TopekaTopeka, Kansas  66606
Highland ClinicShreveport, Louisiana  71105
Kansas City Veterans Affairs Medical CenterKansas City, Missouri  64128
Highland HospitalRochester, New York  14620
Audie L Murphy Veterans Affairs HospitalSan Antonio, Texas  78209
University HospitalSan Antonio, Texas  78229
Olathe Cancer CenterOlathe, Kansas  66061
University of Colorado Cancer Center - Anschutz Cancer PavilionAurora, Colorado  80045
Denver Veterans Administration Medical CenterDenver, Colorado  80220
The Shaw Regional Cancer CenterEdwards, Colorado  81632
Montrose Memorial HospitalMontrose, Colorado  81401
Saint Bernards Regional Medical CenterJonesboro, Arkansas  72401
Mount Clemens Regional Medical CenterMount Clemens, Michigan  48043
Arnot Ogden Medical CenterElmira, New York  14905
University of Tennessee - MemphisMemphis, Tennessee  38163
Southwest Oncology GroupSan Antonio, Texas  78245
Edward Hospital/Cancer CenterNaperville, Illinois  60540
Promise Regional Medical Center-HutchinsonHutchinson, Kansas  65702
Portland Veterans Administration Medical CenterPortland, Oregon  97239