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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2016 by Barbara Ann Karmanos Cancer Institute
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Shirish M. Gadgeel, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier:
NCT01958372
First received: October 7, 2013
Last updated: February 8, 2016
Last verified: February 2016
  Purpose
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.

Condition Intervention Phase
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
Dietary Supplement: soy isoflavones
Drug: cisplatin
Drug: etoposide
Drug: pemetrexed disodium
Radiation: radiation therapy
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Thoracic Radiotherapy and Concurrent Chemotherapy With Soy Isoflavones in Stage III NSCLC (Non-Small Cell Lung Cancer) Patients

Resource links provided by NLM:


Further study details as provided by Barbara Ann Karmanos Cancer Institute:

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 [ Time Frame: Up to 90 days ] [ Designated as safety issue: Yes ]
  • Survival proportion [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Grade 3-4 toxicity rate graded according to NCI CTCAE version 4.0 [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Point and exact confidence interval estimates of the (complete + partial) response rate will be computed.

  • Time to tumor progression (TTP) [ Time Frame: From the date of registration until the date that PD (progressive disease) or death is first reported, assessed up to 2 years ] [ Designated as safety issue: No ]
    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) [ Time Frame: From the date of registration to the date of death, assessed up to 2 years ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    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).


Estimated Enrollment: 24
Study Start Date: August 2014
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group I (squamous cell histology)
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.
Dietary Supplement: soy isoflavones
Given PO
Drug: cisplatin
Given IV
Drug: etoposide
Given IV
Radiation: radiation therapy
Undergo RT
Experimental: 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.
Dietary Supplement: soy isoflavones
Given PO
Drug: cisplatin
Given IV
Drug: pemetrexed disodium
Given IV
Radiation: radiation therapy
Undergo RT

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT01958372

Locations
United States, Michigan
Karmanos Cancer Institute at McLaren Bay Region Recruiting
Bay City, Michigan, United States, 48706
Contact: John Bachman, R.N., CCRP    989-667-2389    John.bachman@mclaren.org   
Principal Investigator: David Cook, M.D.         
Sub-Investigator: Jonathan Abramson, M.D.         
Sub-Investigator: Muhammad Moid, M.D.         
Sub-Investigator: Shalini Thoutreddy, M.D.         
Barbara Ann Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Shirish M. Gadgeel    313-576-8753    gadgeels@karmanos.org   
Principal Investigator: Shirish M. Gadgeel         
Sub-Investigator: Gilda Hillman, Ph.D.         
Sub-Investigator: Michael Joiner, Ph.D.         
Sub-Investigator: Harold Kim, M.D.         
Sub-Investigator: Ammar Sukari, M.D.         
Sub-Investigator: Antionette Wozniak, M.D.         
Sub-Investigator: Jordan Maier, M.D.         
Sub-Investigator: Peter Paximadis, M.D.         
Karmanos Cancer Institute at McLaren Lapeer Region Recruiting
Lapeer, Michigan, United States, 48446
Contact: Valentyna Onishchuk, Ph.D.    810-245-5326    Valentyna.onishchuk@mclaren.org   
Principal Investigator: Sai Bikkina, M.D.         
Sub-Investigator: Soe Maunglay, M.D.         
Karmanos Cancer Institute at McLaren Central Michigan Recruiting
Mt. Pleasant, Michigan, United States, 48858
Contact: Stephanie Walczak, B.A., CCRP    979-953-5178    Stephanie.walczak@mclaren.org   
Principal Investigator: Somdev Roy, M.D.         
Sub-Investigator: William E. Naill, M.D.         
Karmanos Cancer Institute at McLaren Northern Recruiting
Petoskey, Michigan, United States, 49770
Contact: Sandy Sampson, R.N., O.C.N.    231-487-7380    ssampson@northernhealth.org   
Contact: Betsy Johnson, R.N.    231-487-7966    bjohnson@northernhealth.org   
Principal Investigator: Thomas Boike, M.D.         
Sub-Investigator: Lisa Galloway, M.D.         
Sub-Investigator: Ervin Hire, M.D.         
Sub-Investigator: Irene Connolly, M.D.         
Sub-Investigator: Timothy Cox, M.D.         
Sub-Investigator: Elena Coppola, D.O.         
Sub-Investigator: Isaac Kaufman, M.D.         
Sponsors and Collaborators
Barbara Ann Karmanos Cancer Institute
National Cancer Institute (NCI)
Investigators
Principal Investigator: Shirish Gadgeel Barbara Ann Karmanos Cancer Institute
  More Information

Responsible Party: Shirish M. Gadgeel, Principal Investigator, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier: NCT01958372     History of Changes
Other Study ID Numbers: 2013-021  NCI-2013-01835  1307012220  2013-021  P30CA022453 
Study First Received: October 7, 2013
Last Updated: February 8, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Adenocarcinoma
Adenocarcinoma, Bronchiolo-Alveolar
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Etoposide phosphate
Cisplatin
Pemetrexed
Etoposide
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on August 25, 2016