Stereotactic Boost for Locally Advanced Non-Small Cell Lung Cancer

This study has been terminated.
(Slow accrual due to restrictive eligibility criteria)
Sponsor:
Collaborator:
Brigham and Women's Hospital
Information provided by (Responsible Party):
Raymond H. Mak, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT01222572
First received: October 8, 2010
Last updated: October 18, 2014
Last verified: October 2014
  Purpose

In this research study the investigators are looking for the highest dose of a stereotactic radiation boost that can be given safely. Because stereotactic radiation is so precise, the investigators are testing whether it can be used to increase the dose to the primary tumor without significantly increasing the side effects the participant experiences; the goal is to improve the likelihood of killing the tumor.


Condition Intervention Phase
Non-small Cell Lung Cancer
Lung Cancer
NSCLC
Radiation: Stereotactic boost
Radiation: Conventional RT
Drug: Etoposide
Drug: Cisplatin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Stereotactic Boost for Locally Advanced Non-Small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) [ Time Frame: 7-week chemoradiotherapy period and the subsequent 8-week recovery period ] [ Designated as safety issue: Yes ]

    The MTD is determined by the number of patients who experience a dose limiting toxicity (DLT). The MTD is defined as the highest dose at which fewer than one-third of patients experience a DLT. If no DLTs are observed, the MTD is not reached.

    DLTs were defined as follows (CTCAE v4.0):

    Grade 2 non-hematologic toxicities: Myelitis; Esophageal fistula, perforation, hemorrhage

    Grade 3 non-hematologic toxicities considered to be a direct result of therapy:

    Radiation pneumonitis; Pericarditis, pericardial effusion, pericardial tamponade; Esophageal necrosis, stenosis, ulcer; Dyspnea; Myelitis Grade 4 non-hematologic toxicities: Radiation pneumonitis; Pericarditis, pericardial effusion, pericardial tamponade; Esophagitis (not due to mediastinal irradiation unrelated to the stereotactic boost), esophageal necrosis, stenosis, ulcer; Dyspnea; Myelitis Grade 5 non-hematologic toxicity: Any



Enrollment: 1
Study Start Date: December 2010
Study Completion Date: October 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Stereotactic Boost to Chemoradiotherapy (Dose Level 1)

Chemotherapy: Etoposide 50 mg/m2, d1-5, 29-33 and Cisplatin 50 mg/m2, d1, 8, 29, 36; Conventional RT Dose to Primary: 54 Gy; Stereotactic Boost to Primary: 10 Gy; Total Dose to Primary: 64 Gy

- Patients were to start radiation to the primary tumor site and to the lymph nodes and chemotherapy in the same week. The treatment was identical to standard chemotherapy and radiation treatment until the 5th week. During the fifth week, patents would undergo another radiation mapping session to prepare for the stereotactic boost. After that, the radiation treatments to the lymph nodes would continue but the radiation treatment to the primary cancer site would stop until the last week (week 7). During week 7, participants would receive 2 doses of stereotactic radiotherapy to the site of the primary tumor instead of the lower doses of radiotherapy that they were treated with up to that point.

Radiation: Stereotactic boost
Other Name: Stereotactic Body Radiotherapy (SBRT)
Radiation: Conventional RT Drug: Etoposide Drug: Cisplatin
Experimental: Stereotactic Boost to Chemoradiotherapy (Dose Level 2)

Chemotherapy: Etoposide 50 mg/m2, d1-5, 29-33 and Cisplatin 50 mg/m2, d1, 8, 29, 36; Conventional RT Dose to Primary: 50 Gy; Stereotactic Boost to Primary: 15 Gy; Total Dose to Primary: 65 Gy

- Patients were to start radiation to the primary tumor site and to the lymph nodes and chemotherapy in the same week. The treatment was identical to standard chemotherapy and radiation treatment until the 5th week. During the fifth week, patents would undergo another radiation mapping session to prepare for the stereotactic boost. After that, the radiation treatments to the lymph nodes would continue but the radiation treatment to the primary cancer site would stop until the last week (week 7). During week 7, participants would receive 2 doses of stereotactic radiotherapy to the site of the primary tumor instead of the lower doses of radiotherapy that they were treated with up to that point.

Radiation: Stereotactic boost
Other Name: Stereotactic Body Radiotherapy (SBRT)
Radiation: Conventional RT Drug: Etoposide Drug: Cisplatin
Experimental: Stereotactic Boost to Chemoradiotherapy (Dose Level 3)

Chemotherapy: Etoposide 50 mg/m2, d1-5, 29-33 and Cisplatin 50 mg/m2, d1, 8, 29, 36; Conventional RT Dose to Primary: 46 Gy; Stereotactic Boost to Primary: 20 Gy; Total Dose to Primary: 66 Gy

- Patients were to start radiation to the primary tumor site and to the lymph nodes and chemotherapy in the same week. The treatment was identical to standard chemotherapy and radiation treatment until the 5th week. During the fifth week, patents would undergo another radiation mapping session to prepare for the stereotactic boost. After that, the radiation treatments to the lymph nodes would continue but the radiation treatment to the primary cancer site would stop until the last week (week 7). During week 7, participants would receive 2 doses of stereotactic radiotherapy to the site of the primary tumor instead of the lower doses of radiotherapy that they were treated with up to that point.

Radiation: Stereotactic boost
Other Name: Stereotactic Body Radiotherapy (SBRT)
Radiation: Conventional RT Drug: Etoposide Drug: Cisplatin

Detailed Description:

Primary Objectives Phase I: Determination of the MTD and dose-limiting toxicities of a stereotactic boost to chemoradiotherapy for stage II/III non-small cell lung cancer.

Phase II: Two-year local control rate

Secondary Objectives

  • To evaluate the safety and tolerability of a stereotactic boost to chemoradiotherapy.
  • To determine the 2-year overall survival.
  • To determine the 2-year disease-free survival.
  • To determine the 2-year regional control rate.
  • To characterize the change in pulmonary function tests over the first 2 years after chemoradiotherapy.

Statistical Design The Phase I study followed a standard 3+3 dose escalation design. Three dose levels were evaluated. The DLT observation period was the 7-week chemoradiotherapy period and the subsequent 8-week recovery period.

To better study the toxicity at the MTD of the stereotactic boost, there was a 10 patient expansion cohort.The primary endpoint of the phase II portion of the study was two-year local failure rate of the protocol treatment. Local failure was defined as biopsy-proven recurrent disease, or if a biopsy was not attainable, by increasing FDG-avidity on PET-CT on 2 consecutive scans at least 1 month apart. Based on prior studies, a 2-year local failure rate of 15% would be worthy of further study, while a 2-year local failure rate of 35% would not justify further utilization of the treatment. With 32 eligible patients on this study, the treatment will be deemed promising if at least 25 patients are free of local failure at 2 years. Using this design, there was an 8% probability of declaring the treatment worthy of further study if the true 2-year local failure rate was 35%, and a 90% probability of declaring the treatment worthy of further study if the true 2-year local failure rate was 15% by using a one-sided one-sample exact binomial test.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed stage II or stage III non-small cell lung cancer, or stage IV non-small cell lung cancer that will be treated with curative intent
  • Evaluated by a surgeon and deemed inoperable
  • Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension as 10mm or greater with chest CT scan.
  • No active malignancy within the past 5 years, except for non-melanoma skin cancers or carcinoma in situ of the cervix
  • 18 years or older
  • Life expectancy of greater then 6 months
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
  • Normal organ and marrow function as outlined in the protocol
  • Forced expiratory volume (FEV1) of 1 L or greater OR 50% or greater of predicted

Exclusion Criteria:

  • Primary tumor size greater then 6cm
  • Prior history of thoracic radiotherapy
  • May not be receiving any other study agents
  • History of pulmonary fibrosis
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to cisplatin or etoposide
  • Primary tumor < 1.5 cm beyond hilar lymphadenopathy (if any) and 1.5 cm from proximal bronchial tree, defined as the trachea, right and left mainstem bronchus, and lobar bronchi until the 1st lobar segment
  • Uncontrolled intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant or breast feeding women
  • Individuals with a history of a different malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin
  • Human immunodeficiency virus (HIV)-positive individuals on combination antiretroviral therapy
  • Patients who are planned to receive the following medication: granulocyte colony-stimulating factor (G-CSF), bevacizumab, cetuximab, cyclosporine, anti-tumor necrosis factor agents, amifostine.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01222572

Locations
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Investigators
Principal Investigator: Raymond H. Mak, MD Dana-Farber Cancer Institute/Brigham and Women's Hospital
  More Information

No publications provided

Responsible Party: Raymond H. Mak, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT01222572     History of Changes
Other Study ID Numbers: 10-240
Study First Received: October 8, 2010
Results First Received: August 25, 2014
Last Updated: October 18, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Dana-Farber Cancer Institute:
radiation therapy
stereotactic radiotherapy
stereotactic boost

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Etoposide phosphate
Cisplatin
Etoposide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 19, 2014