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Summary

for people ages 18 years and up (full criteria)
at San Francisco, California and other locations
study started

Description

Summary

This randomized phase II trial studies how well chemotherapy and radiation therapy given with or without metformin hydrochloride works in treating patients with stage III non-small cell lung cancer. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Metformin hydrochloride may shrink tumors and keep them from coming back. It is not yet known whether chemotherapy and radiation therapy is more effective when given with or without metformin hydrochloride in treating stage III non-small cell lung cancer.

Official Title

Randomized Phase II Trial of Concurrent Chemoradiotherapy +/- Metformin HCL in Locally Advanced NSCLC

Details

PRIMARY OBJECTIVES:

I. To determine whether metformin hydrochloride (MET) added to chemoradiotherapy can improve progression-free survival (PFS) in patients with locally advanced non-small cell lung cancer (NSCLC).

SECONDARY OBJECTIVES:

I. Determine the effects of MET on overall survival (OS), time to local-regional progression (LRP), and time to distant metastasis (DM).

II. Evaluate the effect of MET on chemoradiotherapy toxicity (Common Terminology Criteria for Adverse Events, version 4 [CTCAE, v. 4]) within 1 year of completion of all treatment.

III. Collect biospecimens to develop biomarkers of MET activity.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive paclitaxel intravenously (IV) over 1 hour and carboplatin IV over 30 minutes on days 1, 8, 15, 22, 29, and 36 and undergo radiation therapy (3-dimensional conformal radiation therapy [3D-CRT] or intensity modulated radiation therapy [IMRT]) once daily (QD) 5 days a week for 6 weeks. Beginning 28-42 days after completion of radiation therapy, patients receive consolidation chemotherapy comprising paclitaxel IV and carboplatin IV on days 1 and 22. Treatment with consolidation chemotherapy repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive metformin hydrochloride orally (PO) twice daily (BID) or thrice daily (TID) for 14 days. Beginning on day 15, patients undergo radiation therapy and receive paclitaxel and carboplatin as in Arm I, and receive metformin hydrochloride BID or TID for 6 weeks. Beginning 28-42 days after completion of radiation therapy, patients receive consolidation chemotherapy as in Arm I and metformin hydrochloride PO BID or TID for 10 weeks.

After completion of study treatment, patients are followed up at 4-6 weeks, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Keywords

Adenosquamous Lung Carcinoma Bronchioloalveolar Carcinoma Large Cell Lung Carcinoma Lung Adenocarcinoma Non-Small Cell Lung Carcinoma Recurrent Non-Small Cell Lung Carcinoma Squamous Cell Lung Carcinoma Stage IIIA Non-Small Cell Lung Cancer Stage IIIB Non-Small Cell Lung Cancer Paclitaxel Albumin-Bound Paclitaxel Carboplatin Metformin

Eligibility

You can join if…

Open to people ages 18 years and up

  • Pathologically (histologically or cytologically) proven diagnosis of stage IIIA or IIIB non-small cell lung cancer within 84 days of registration; eligible histologies include adenocarcinoma, adenosquamous, large cell carcinoma, squamous carcinoma,non-lobar and non-diffuse bronchoalveolar cell carcinoma or non-small cell lung cancer not otherwise specified [NOS])
  • Patients must have measurable disease
  • Patients must have unresectable disease, be medically inoperable, or unwilling to undergo surgical management
  • Appropriate stage for protocol entry, including no distant metastases, based upon the following minimum diagnostic workup:
  • History/physical examination, including documentation of height, weight, body surface area [BSA], and vital signs, within 30 days prior to registration
  • Computed tomography (CT) with IV contrast or magnetic resonance imaging (MRI)imaging (if CT scan with contrast is medically contraindicated) of the lung and upper abdomen through the adrenal glands, required within 45 days prior to registration (recommended within 30 days prior to registration
  • MRI of the brain with contrast (or CT with contrast if MRI is medically contraindicated) within 30 days prior to registration; note: the use of intravenous contrast is required for the MRI or CT; an MRI without contrast is only permitted if the patient has a contrast allergy
  • Whole-body fludeoxyglucose F 18 (FDG)-positron emission tomography (PET)/CT required within 45 days prior to registration (recommended within 30 days prior to registration; note: patients do not need to have a separate CT of the chest and upper abdomen with contrast if PET/CT imaging includes a high quality CT with contrast
  • Zubrod performance status 0-1
  • Absolute neutrophil count (ANC)>= 1,500 cells/mm^3
  • Platelets>= 100,000 cells/mm^3
  • Hemoglobin>= 8.0 g/dl (note: the use of transfusion or other intervention to achieve hemoglobin [Hgb]>= 8.0 g/dl is acceptable)
  • Serum creatinine within normal institutional limits or creatinine clearance must be at least 60 ml/min
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) for the institution
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN for the institution
  • Alkaline phosphatase =< 2.5 x ULN for the institution
  • Fasting blood glucose =< 125 mg/dL within 14 days prior to registration
  • Serum albumin> 3.0 g/dl within 14 days prior to registration
  • For women of childbearing potential, a serum pregnancy test within 72 hours prior to registration
  • Patients with post-obstructive pneumonia are eligible provided they no longer require intravenous antibiotics at registration
  • Patients must be at least 3 weeks from prior thoracotomy (if performed)
  • If a pleural effusion is present, the following criteria must be met at registration to exclude malignant involvement (incurable M1a disease):
  • When pleural fluid is visible on both the CT scan and on a chest x-ray, a pleuracentesis is required to confirm that the pleural fluid is cytologically negative
  • Effusions that are minimal (i.e. not visible under ultrasound guidance) and that are too small to safely tap are eligible
  • Women of childbearing potential and male participants must practice adequate contraception throughout the study
  • Patient must provide study specific informed consent prior to study entry

You CAN'T join if...

  • Patients with mixed small cell and non-small cell histologies
  • Patients with distant metastasis
  • Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years (for example, carcinoma in situ of the breast, oral cavity,or cervix are all permissible)
  • Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable
  • Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
  • Patients currently using metformin (metformin hydrochloride), other oral hypoglycemic agents or insulin
  • Patients with any history of allergic reaction to paclitaxel or other taxanes or carboplatin
  • Patients with a history of chronic kidney disease or lactic acidosis
  • Patients with>= 10% weight loss within the past month
  • Severe, active co-morbidity, defined as follows:
  • Diagnosis of type I or type II diabetes mellitus
  • Uncontrolled neuropathy>= grade 2 regardless of cause
  • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
  • Transmural myocardial infarction within the last 6 months
  • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
  • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration
  • Severe hepatic disease, defined as a diagnosis of Child-Pugh class B or C hepatic disease
  • Human immunodeficiency virus (HIV) positive with cluster of differentiation (CD)4 count < 200 cells/microliter; note that patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count>= 200 cells/microliter within 30 days prior to registration; note also that HIV testing is not required for eligibility for this protocol
  • End-stage renal disease (ie, on dialysis or dialysis has been recommended)
  • Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception

Locations

  • Kaiser Permanente Cancer Treatment Center
    South San Francisco, California, 94080, United States
  • Kaiser Permanente Oakland-Broadway
    Oakland, California, 94611, United States
  • Eden Hospital Medical Center
    Castro Valley, California, 94546, United States
  • Rohnert Park Cancer Center
    Rohnert Park, California, 94928, United States
  • Sutter Cancer Centers Radiation Oncology Services-Vacaville
    Vacaville, California, 95687, United States
  • Sutter General Hospital
    Sacramento, California, 95816, United States
  • Kaiser Permanente-Rancho Cordova Cancer Center
    Rancho Cordova, California, 95670, United States
  • The Permanente Medical Group-Roseville Radiation Oncology
    Roseville, California, 95678, United States
  • Sutter Cancer Centers Radiation Oncology Services-Roseville
    Roseville, California, 95661, United States
  • Sutter Cancer Centers Radiation Oncology Services-Cameron Park
    Cameron Park, California, 95682, United States
  • Sutter Cancer Centers Radiation Oncology Services-Auburn
    Auburn, California, 95603, United States

Details

Status
in progress, not accepting new patients
Start Date
Sponsor
NRG Oncology
ID
NCT02186847
Phase
Phase 2
Study Type
Interventional
Last Updated
December 1, 2016