Stereotactic Boost for Locally Advanced Non-Small Cell Lung Cancer

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Primary Purpose

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Stereotactic boost

Conventional RT

Etoposide

Cisplatin

About this trial

This is an interventional treatment trial for Non-small Cell Lung Cancer focused on measuring radiation therapy, stereotactic radiotherapy, stereotactic boost

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Dana-Farber Cancer Institute

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Stereotactic Boost to Chemoradiotherapy (Dose Level 1)

Stereotactic Boost to Chemoradiotherapy (Dose Level 2)

Stereotactic Boost to Chemoradiotherapy (Dose Level 3)

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

Maximum Tolerated Dose (MTD)

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

Secondary Outcome Measures

Full Information

NCT ID

NCT01222572

First Posted

October 8, 2010

Last Updated

May 11, 2015

Sponsor

Dana-Farber Cancer Institute

Collaborators

Brigham and Women's Hospital

1. Study Identification

Unique Protocol Identification Number

NCT01222572

Brief Title

Stereotactic Boost for Locally Advanced Non-Small Cell Lung Cancer

Official Title

Stereotactic Boost for Locally Advanced Non-Small Cell Lung Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

May 2015

Overall Recruitment Status

Terminated

Why Stopped

Slow accrual due to restrictive eligibility criteria

Study Start Date

December 2010 (undefined)

Primary Completion Date

March 2012 (Actual)

Study Completion Date

October 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Dana-Farber Cancer Institute

Collaborators

Brigham and Women's Hospital

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Non-small Cell Lung Cancer, Lung Cancer, NSCLC

Keywords

radiation therapy, stereotactic radiotherapy, stereotactic boost

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

1 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Stereotactic Boost to Chemoradiotherapy (Dose Level 1)

Arm Type

Experimental

Arm Description

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.

Arm Title

Stereotactic Boost to Chemoradiotherapy (Dose Level 2)

Arm Type

Experimental

Arm Description

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.

Arm Title

Stereotactic Boost to Chemoradiotherapy (Dose Level 3)

Arm Type

Experimental

Arm Description

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.

Intervention Type

Radiation

Intervention Name(s)

Stereotactic boost

Other Intervention Name(s)

Stereotactic Body Radiotherapy (SBRT)

Intervention Type

Radiation

Intervention Name(s)

Conventional RT

Intervention Type

Drug

Intervention Name(s)

Etoposide

Intervention Type

Drug

Intervention Name(s)

Cisplatin

Primary Outcome Measure Information:

Title

Maximum Tolerated Dose (MTD)

Description

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

Time Frame

7-week chemoradiotherapy period and the subsequent 8-week recovery period

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Raymond H. Mak, MD

Organizational Affiliation

Dana-Farber Cancer Institute/Brigham and Women's Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Dana-Farber Cancer Institute

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02115

Country

United States

Non-small Cell Lung Cancer, Lung Cancer, NSCLC

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial