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

October 8, 2010
October 18, 2014
December 2010
March 2012   (final data collection date for primary outcome measure)
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

  • Phase I: Maximally Tolerated Dose (MTD) of Stereotactic Boost Radiotherapy [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    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 Following Stereotactic Boost Radiotherapy [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Local failure is defined as biopsy-proven recurrent disease, or if a biopsy is not attainable, by increasing fludeoxyglucose (FDG)-avidity on positron emission tomography-computed tomography (PET-CT) on 2 consecutive scans at least 1 month apart
Complete list of historical versions of study NCT01222572 on ClinicalTrials.gov Archive Site
Not Provided
  • Risk of Grade 2-3 Radiation Pneumonitis [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    To evaluate the risk of radiation pneumonitis following stereotactic boost radiotherapy
  • Overall Survival Rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To determine the 2-year overall survival following stereotactic boost radiotherapy
  • Disease-free Survival Rate [ Time Frame: 2 year ] [ Designated as safety issue: No ]
    To determine the 2-year disease-free survival
  • Regional Control Rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To determine the 2-year regional control rate.
  • Change in Pulmonary Function [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To characterize the change in pulmonary function tests over the first 2 years after chemoradiotherapy
Not Provided
Not Provided
 
Stereotactic Boost for Locally Advanced Non-Small Cell Lung Cancer
Stereotactic Boost for Locally Advanced Non-Small Cell Lung Cancer

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.

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.

Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Non-small Cell Lung Cancer
  • Lung Cancer
  • NSCLC
  • Radiation: Stereotactic boost
    Other Name: Stereotactic Body Radiotherapy (SBRT)
  • Radiation: Conventional RT
  • Drug: Etoposide
  • Drug: Cisplatin
  • 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.

    Interventions:
    • Radiation: Stereotactic boost
    • 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.

    Interventions:
    • Radiation: Stereotactic boost
    • 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.

    Interventions:
    • Radiation: Stereotactic boost
    • Radiation: Conventional RT
    • Drug: Etoposide
    • Drug: Cisplatin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
1
October 2012
March 2012   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01222572
10-240
Yes
Raymond H. Mak, Dana-Farber Cancer Institute
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Principal Investigator: Raymond H. Mak, MD Dana-Farber Cancer Institute/Brigham and Women's Hospital
Dana-Farber Cancer Institute
October 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP