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Radiation Therapy, Chemotherapy, and Soy Isoflavones in Treating Patients With Stage IIIA-IIIB Non-Small Cell Lung Cancer

Primary Purpose

Adenocarcinoma of the Lung, Adenosquamous Cell Lung Cancer, Bronchoalveolar Cell Lung Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
soy isoflavones
cisplatin
etoposide
pemetrexed disodium
radiation therapy
Sponsored by
Barbara Ann Karmanos Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adenocarcinoma of the Lung

Eligibility Criteria

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

Inclusion Criteria:

  • Histologic or cytologic diagnosis of stage III non-small cell lung cancer; patients will need to meet the following criteria for stage IIIA or IIIB diagnosis:

    • IIIA

      • Histologic or cytologic diagnosis of ipsilateral mediastinal lymph node involvement, or
      • Tumors greater than 7 cm or with chest wall invasion, or involvement of one of the following diaphragm, phrenic nerve, mediastinal pleura or parietal pericardium with hilar or mediastinal lymph node involvement
      • More than one mediastinal lymph node enlarged on computed tomography (CT) scan and the same lymph nodes positive on positron emission tomography (PET) scans or
      • Paralyzed left vocal cord with separate lung primary distinct from the aorto-pulmonary lymph nodes on the CT scan

    • IIIB

      • Histologic or cytologic diagnosis of N3 lymph node involvement; or
      • Enlarged N3 lymph nodes on CT scan that are positive on PET scan as well; patient must not have extension of lymph node involvement to cervical lymph nodes other than supraclavicular lymph nodes; or
      • Right sided primary with left vocal cord paralysis; or
      • Evidence of tumor extension into the mediastinum and/or mediastinal structures either at the time of mediastinoscopy, bronchoscopy or on CT scans
      • Patients with a nodules in the same lung but no other areas of involvement
      • Patients with prior surgically resected stage I NSCLC who did not receive any adjuvant therapy, who now have stage IIIA or B NSCLC will be eligible
  • Southwestern Oncology Group (SWOG) performance status 0 or 1
  • Absolute neutrophil count of > 1.5 x 10^9/L
  • Platelet count > 100,000 x 10^9/L
  • Serum creatinine =< 1.5 times the institutional upper limit of normal (ULN)
  • Calculated creatinine clearance (Cockcroft-Gault formula) of >= 45mL/min
  • Serum bilirubin > ULN
  • Transaminases (serum glutamic oxaloacetic transaminase [SGOT] and/or serum glutamate pyruvate transaminase [SGPT]) > 1.5 times institutional ULN
  • Alkaline phosphatase >= 2.5 times ULN
  • Forced expiratory volume in one second (FEV1) of >= 1 liter and diffusion capacity of carbon monoxide (DLCO) >= 40% of predicted
  • Patient should undergo brain imaging (CT scan or magnetic resonance imaging [MRI ]) to rule out brain metastases
  • Signed informed consent that details the investigational nature of the study according to institutional and federal guidelines
  • Registered with Clinical Trials Office at Karmanos Cancer Institute/Wayne State University

Exclusion Criteria:

  • Prior chemotherapy, radiation for any malignancy in which they received any thoracic radiotherapy
  • Patients with concurrent malignancy; patients with prior or concurrent malignancy will be allowed as long as the treating physician considers it unlikely to impact the clinical outcome of the patient
  • Patients with peripheral neuropathy > 2
  • Serious medical illness including but not limited to uncontrolled congestive heart failure, uncontrolled angina, myocardial infarction or cerebrovascular event with 6 months of registration, history of chronic active hepatitis or history of human immunodeficiency virus (HIV) or an active bacterial infection will not be eligible
  • Inability or unwillingness to take folic acid or vitamin B12 or dexamethasone
  • Pregnant or lactating women; all pre-menopausal and peri-menopausal women should have a urine test for pregnancy within a week of starting therapy; all patients of child bearing potential should agree to use an effective contraceptive method
  • Patients should not participate in any other therapeutic investigational study while taking part in this study
  • Patients on warfarin will not be allowed on the study; patient on low molecular heparin or anti direct factor Xa inhibitor (Xa) drugs will be allowed
  • Patients with a soy allergy will be excluded

Sites / Locations

  • Karmanos Cancer Institute at McLaren Bay Region
  • Barbara Ann Karmanos Cancer Institute
  • Karmanos Cancer Institute at McLaren Lapeer Region
  • Karmanos Cancer Institute at McLaren Central Michigan
  • Karmanos Cancer Institute at McLaren Northern

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Group I (squamous cell histology)

Group II (non-squamous cell histology)

Arm Description

Patients receive etoposide IV over 1 hour on days 1-5 and 29-33, cisplatin IV over 1 hour on days 1, 8, 29, and 36, and undergo RT 5 days a week for 6.6 weeks. Within 48 hours of initiating treatment, patients receive soy isoflavones PO daily on days 1-90.

Patients receive pemetrexed disodium IV over 10 minutes on days 1, 22, and 43 and cisplatin IV over 1 hour on days 1, 22, and 43. Patients also undergo RT and receive soy isoflavones as in Group I.

Outcomes

Primary Outcome Measures

Safety, in terms of dose-limiting toxicity of adding oral soy isoflavone supplementation to concurrent chemotherapy and radiotherapy, graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4
Survival proportion

Secondary Outcome Measures

Grade 3-4 toxicity rate graded according to NCI CTCAE version 4.0
Point and exact confidence interval estimates of the grade 3-4 toxicity rate will be computed for each type of toxicity encountered.
Response (complete response [CR] and partial response [PR]) rate according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Point and exact confidence interval estimates of the (complete + partial) response rate will be computed.
Time to tumor progression (TTP)
TTP will be estimated using standard Kaplan-Meier methods for censored data, from which the median and other statistics of interest will be calculated (e.g., rates at 3 months, 6 months, 12 months).
Overall survival (OS)
OS will be estimated using standard Kaplan-Meier methods for censored data, from which the median and other statistics of interest will be calculated (e.g., rates at 3 months, 6 months, 12 months).
Response duration
Response duration will be estimated using standard Kaplan-Meier methods for censored data, from which the median and other statistics of interest will be calculated (e.g., rates at 3 months, 6 months, 12 months).

Full Information

First Posted
October 7, 2013
Last Updated
November 19, 2020
Sponsor
Barbara Ann Karmanos Cancer Institute
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT01958372
Brief Title
Radiation Therapy, Chemotherapy, and Soy Isoflavones in Treating Patients With Stage IIIA-IIIB Non-Small Cell Lung Cancer
Official Title
Phase I Study of Thoracic Radiotherapy and Concurrent Chemotherapy With Soy Isoflavones in Stage III NSCLC (Non-Small Cell Lung Cancer) Patients
Study Type
Interventional

2. Study Status

Record Verification Date
November 2020
Overall Recruitment Status
Completed
Study Start Date
August 2014 (undefined)
Primary Completion Date
October 9, 2017 (Actual)
Study Completion Date
November 11, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Barbara Ann Karmanos Cancer Institute
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
This phase I trial studies the side effects of soy isoflavones when given together with radiation therapy and chemotherapy in treating patients with stage IIIA-IIIB non-small cell lung cancer. Radiation therapy uses high energy x rays to kill tumor cells. Drugs used in chemotherapy, such as cisplatin, pemetrexed sodium, and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Soy isoflavones may help radiation therapy, cisplatin, pemetrexed sodium, and etoposide work better by making tumor cells more sensitive to the drug. Soy isoflavones may also protect normal cells from the side effects of radiation therapy and chemotherapy.
Detailed Description
PRIMARY OBJECTIVES: I. To evaluate the safety of adding oral soy isoflavone to concurrent chemotherapy and radiotherapy for the treatment of patients with unresectable stage III non-small cell lung cancer (NSCLC). OUTLINE: Patients are assigned to 1 of 2 treatment groups. GROUP I (SQUAMOUS CELL HISTOLOGY): Patients receive etoposide intravenously (IV) over 1 hour on days 1-5 and 29-33, cisplatin IV over 1 hour on days 1, 8, 29, and 36, and undergo radiation therapy (RT) 5 days a week for 6.6 weeks. Within 48 hours of initiating treatment, patients receive soy isoflavones orally (PO) daily on days 1-90. GROUP II (NON-SQUAMOUS CELL HISTOLOGY): Patients receive pemetrexed disodium IV over 10 minutes on days 1, 22, and 43 and cisplatin IV over 1 hour on days 1, 22, and 43. Patients also undergo RT and receive soy isoflavones as in Group I. After completion of study treatment, patients are followed up at 4 weeks and then every 4 months for 1 year, every 6 months for 1 year, and then yearly thereafter.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adenocarcinoma of the Lung, Adenosquamous Cell Lung Cancer, Bronchoalveolar Cell Lung Cancer, Large Cell Lung Cancer, Recurrent Non-small Cell Lung Cancer, Squamous Cell Lung Cancer, Stage IIIA Non-small Cell Lung Cancer, Stage IIIB Non-small Cell Lung Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
11 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group I (squamous cell histology)
Arm Type
Experimental
Arm Description
Patients receive etoposide IV over 1 hour on days 1-5 and 29-33, cisplatin IV over 1 hour on days 1, 8, 29, and 36, and undergo RT 5 days a week for 6.6 weeks. Within 48 hours of initiating treatment, patients receive soy isoflavones PO daily on days 1-90.
Arm Title
Group II (non-squamous cell histology)
Arm Type
Experimental
Arm Description
Patients receive pemetrexed disodium IV over 10 minutes on days 1, 22, and 43 and cisplatin IV over 1 hour on days 1, 22, and 43. Patients also undergo RT and receive soy isoflavones as in Group I.
Intervention Type
Dietary Supplement
Intervention Name(s)
soy isoflavones
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
cisplatin
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
etoposide
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
pemetrexed disodium
Intervention Description
Given IV
Intervention Type
Radiation
Intervention Name(s)
radiation therapy
Intervention Description
Undergo RT
Primary Outcome Measure Information:
Title
Safety, in terms of dose-limiting toxicity of adding oral soy isoflavone supplementation to concurrent chemotherapy and radiotherapy, graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4
Time Frame
Up to 90 days
Title
Survival proportion
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Grade 3-4 toxicity rate graded according to NCI CTCAE version 4.0
Description
Point and exact confidence interval estimates of the grade 3-4 toxicity rate will be computed for each type of toxicity encountered.
Time Frame
Up to 2 years
Title
Response (complete response [CR] and partial response [PR]) rate according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Description
Point and exact confidence interval estimates of the (complete + partial) response rate will be computed.
Time Frame
Up to 2 years
Title
Time to tumor progression (TTP)
Description
TTP will be estimated using standard Kaplan-Meier methods for censored data, from which the median and other statistics of interest will be calculated (e.g., rates at 3 months, 6 months, 12 months).
Time Frame
From the date of registration until the date that PD (progressive disease) or death is first reported, assessed up to 2 years
Title
Overall survival (OS)
Description
OS will be estimated using standard Kaplan-Meier methods for censored data, from which the median and other statistics of interest will be calculated (e.g., rates at 3 months, 6 months, 12 months).
Time Frame
From the date of registration to the date of death, assessed up to 2 years
Title
Response duration
Description
Response duration will be estimated using standard Kaplan-Meier methods for censored data, from which the median and other statistics of interest will be calculated (e.g., rates at 3 months, 6 months, 12 months).
Time Frame
From the time that measurement criteria are first met for CR until the date that PD is objectively documented, assessed up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologic or cytologic diagnosis of stage III non-small cell lung cancer; patients will need to meet the following criteria for stage IIIA or IIIB diagnosis: IIIA Histologic or cytologic diagnosis of ipsilateral mediastinal lymph node involvement, or Tumors greater than 7 cm or with chest wall invasion, or involvement of one of the following diaphragm, phrenic nerve, mediastinal pleura or parietal pericardium with hilar or mediastinal lymph node involvement More than one mediastinal lymph node enlarged on computed tomography (CT) scan and the same lymph nodes positive on positron emission tomography (PET) scans or Paralyzed left vocal cord with separate lung primary distinct from the aorto-pulmonary lymph nodes on the CT scan IIIB Histologic or cytologic diagnosis of N3 lymph node involvement; or Enlarged N3 lymph nodes on CT scan that are positive on PET scan as well; patient must not have extension of lymph node involvement to cervical lymph nodes other than supraclavicular lymph nodes; or Right sided primary with left vocal cord paralysis; or Evidence of tumor extension into the mediastinum and/or mediastinal structures either at the time of mediastinoscopy, bronchoscopy or on CT scans Patients with a nodules in the same lung but no other areas of involvement Patients with prior surgically resected stage I NSCLC who did not receive any adjuvant therapy, who now have stage IIIA or B NSCLC will be eligible Southwestern Oncology Group (SWOG) performance status 0 or 1 Absolute neutrophil count of > 1.5 x 10^9/L Platelet count > 100,000 x 10^9/L Serum creatinine =< 1.5 times the institutional upper limit of normal (ULN) Calculated creatinine clearance (Cockcroft-Gault formula) of >= 45mL/min Serum bilirubin > ULN Transaminases (serum glutamic oxaloacetic transaminase [SGOT] and/or serum glutamate pyruvate transaminase [SGPT]) > 1.5 times institutional ULN Alkaline phosphatase >= 2.5 times ULN Forced expiratory volume in one second (FEV1) of >= 1 liter and diffusion capacity of carbon monoxide (DLCO) >= 40% of predicted Patient should undergo brain imaging (CT scan or magnetic resonance imaging [MRI ]) to rule out brain metastases Signed informed consent that details the investigational nature of the study according to institutional and federal guidelines Registered with Clinical Trials Office at Karmanos Cancer Institute/Wayne State University Exclusion Criteria: Prior chemotherapy, radiation for any malignancy in which they received any thoracic radiotherapy Patients with concurrent malignancy; patients with prior or concurrent malignancy will be allowed as long as the treating physician considers it unlikely to impact the clinical outcome of the patient Patients with peripheral neuropathy > 2 Serious medical illness including but not limited to uncontrolled congestive heart failure, uncontrolled angina, myocardial infarction or cerebrovascular event with 6 months of registration, history of chronic active hepatitis or history of human immunodeficiency virus (HIV) or an active bacterial infection will not be eligible Inability or unwillingness to take folic acid or vitamin B12 or dexamethasone Pregnant or lactating women; all pre-menopausal and peri-menopausal women should have a urine test for pregnancy within a week of starting therapy; all patients of child bearing potential should agree to use an effective contraceptive method Patients should not participate in any other therapeutic investigational study while taking part in this study Patients on warfarin will not be allowed on the study; patient on low molecular heparin or anti direct factor Xa inhibitor (Xa) drugs will be allowed Patients with a soy allergy will be excluded
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shirish Gadgeel
Organizational Affiliation
Barbara Ann Karmanos Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Karmanos Cancer Institute at McLaren Bay Region
City
Bay City
State/Province
Michigan
ZIP/Postal Code
48706
Country
United States
Facility Name
Barbara Ann Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Karmanos Cancer Institute at McLaren Lapeer Region
City
Lapeer
State/Province
Michigan
ZIP/Postal Code
48446
Country
United States
Facility Name
Karmanos Cancer Institute at McLaren Central Michigan
City
Mount Pleasant
State/Province
Michigan
ZIP/Postal Code
48858
Country
United States
Facility Name
Karmanos Cancer Institute at McLaren Northern
City
Petoskey
State/Province
Michigan
ZIP/Postal Code
49770
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Radiation Therapy, Chemotherapy, and Soy Isoflavones in Treating Patients With Stage IIIA-IIIB Non-Small Cell Lung Cancer

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