Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Hypoglycemic Agents

All Drugs and Chemicals

Pioglitazone

45 mg tablet daily by mouth for six weeks

Giuseppe Giaccone, M.D.

Background:

* Pioglitazone is a drug that belongs to the class of antidiabetic agents called thiazolidinediones. It is approved for treatment of type 2 diabetes mellitus.
* Research suggests that the thiazolidinediones may have anticancer activity that can reduce cancer risk or cause tumors to shrink.

Objectives:

-To test how a pioglitazone works as a treatment of Stage IA to IIB Non-Small Cell Lung Cancer (NSCLC) and to look at the effect of the drug on cancer cells.

Eligibility:

-Patients 18 years of age or older who will undergo surgery for Stage IA to IIB non-small cell lung cancer (NSCLC).

Design:

-The study includes a screening visit to determine eligibility, treatment with pioglitazone, a follow-up visit after 2 to 3 weeks of treatment and a post-surgery visit. Procedures include:

1. Medical history, physical examination, blood tests, electrocardiogram
2. Bronchoscopy to obtain cancer cells. This is done before pioglitazone treatment begins and again during lung surgery. Some patients may also require mediastinoscopy or biopsy to collect cells.
3. Treatment with pioglitazone tablets once a day for at least 2 weeks and no more than 6 weeks, depending on when surgery has been scheduled.
4. Positron emission tomography (PET) scan before starting pioglitazone treatment. National Cancer Institute (NCI) patients also have a follow-up PET scan after treatment but before surgery.

Background:

Lung cancer is the leading cause of cancer deaths in the United States (US). Chemoprevention is an active area of investigation for reducing the burden of this disease. However, the choice of chemopreventive targets requires sufficient human data to justify extensive clinical interventions.

Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a ligand activated nuclear transcription factor that is a key regulator of adipogenic differentiation. PPAR gamma ligands, particularly the thiazolidinedione class of antidiabetic agents exemplified by pioglitazone, are under investigation as chemopreventive agents.

PPAR gamma is expressed in normal lung and in NSCLC. PPAR gamma ligands induce apoptosis in NSCLC cell lines and modulate their differentiation status. Animal carcinogenesis studies, however, show equivocal efficacy in prevention of lung cancer.

Relevant human data are limited to an epidemiologic study showing that lung cancer risk is decreased in diabetics taking thiazolidinediones and a small phase IIa trial of pioglitazone in oral leukoplakia showing an 80% clinical response (partial response (PR)+ complete response (CR)). Further data are needed prior to engaging in a phase II lung chemoprevention trial.

Objectives:

The objectives of this pilot feasibility study are to evaluate the effect of pioglitazone on the expression of multiple biomarkers in NSCLC tumor tissue and in histologically normal and premalignant tissue.

* The primary endpoint will be the effect of pioglitazone on Ki-67, a marker of proliferation, in tumor tissue.
* The secondary objectives are to determine the effects of pioglitazone on multiple biomarkers in tumor, premalignant, and histologically normal bronchial epithelium and in serum:

  * Tumor tissue biomarkers: apoptotic index (AI), cyclin D1, p21/Waf1, PPAR gamma, mucin 1 (MUC1), gelsolin, proline oxidase, 15-hydroxyprostaglandin dehydrogenase (15-PGDH)
  * Premalignant tissue biomarkers: Ki-67, apoptotic index, PPAR gamma
  * Histologically normal tissue biomarkers: Ki-67, PPAR gamma
  * Serum markers affected by pioglitazone; C-reactive protein, CA 15-3
  * Serum tumor markers: carcinoembryonic antigen (CEA), cancer antigen 125 (CA-125)
* Additional secondary objectives are:

  * To evaluate the toxicity and safety of pioglitazone in this patient population,
  * To determine if limited treatment with pioglitazone affects tumor metabolic activity as determined by fludeoxyglucose positron-emission tomography (FDG-PET).

Eligibility:

Adult patients with newly diagnosed histologically confirmed stage Ia-IIb resectable non-small cell lung cancer who are eligible for and scheduled to undergo definitive surgery.

Eastern Cooperative Oncology Group (ECOG) 0-2

Normal organ function

Design:

Open label, multi-center, non-randomized pilot study to evaluate the effect of pioglitazone on the expression of multiple biomarkers in NSCLC tumor tissue and in histologically normal and premalignant tissue obtained from treatment-naive individuals who will receive oral pioglitazone prior to definitive surgery. The primary endpoint is Ki-67 measured in tumor tissue.

Patients will receive pioglitazone 45 mg po qd for a minimum of 2 weeks or a maximum of 6 weeks, with duration of treatment determined by standard of care and scheduling of surgery.

The study will consist of a screening visit, baseline bronchoscopy with tissue acquisition, pioglitazone treatment for 2-6 weeks, a 2-week on-treatment clinic visit, definitive surgical resection with bronchoscopy performed at the time of resection, and a post-surgery visit. Tissue (visually normal and abnormal areas identified during bronchoscopy) and tumor will be obtained at baseline and at the time of surgery. Patients who receive their treatment at NCI will also undergo a follow up FDG-PET scan after a minimum of 2 weeks of pioglitazone treatment.

Up to 25 patients are expected to be enrolled to identify 20 patients with adequate tissue for biomarker analysis.

Pioglitazone to Treat Adults Undergoing Surgery for Non-small Cell Lung Cancer

Pilot Trial of Pioglitazone in Adults Undergoing Surgical Resection of Non-Small Cell Lung Cancer

Antigen ki-67 (Ki-67) will be assessed by immunohistochemistry.

Apoptotic index (A1) will be assessed by terminal deoxynucleotidyl transferase dUTP end labeling (TUNEL) and cyclin D1, p21/Waf1, PPARy, MUC1, gelsolin, proline oxidase, and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) will be assessed by immunohistochemistry.

Here are the number of participants with adverse events. For details about the adverse events see the adverse event module.

Response will be evaluated by FDG-PET. Response is defined as a decrease of standardized uptake values (SUV) of more than one.

Premalignant tissue biomarkers ki-67, apoptotic index and peroxisome proliferator-activated receptor gamma (PPARgamma) will be assessed by immunohistochemistry.

ki-67 and peroxisome proliferator-activated receptor gamma (PPARgamma) will be assessed by immunohistochemistry.

C-reactive protein, cancer antigen 15-3 (CA 15-3), cancer antigen 125 (CA-125) and carcinoembryonic antigen (CEA) will be assessed by immunohistochemistry.

National Cancer Institute (NCI)

Giuseppe Giaccone, M.D./National Cancer Institute

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Study never published; terminated early due to low accrual.

Giuseppe Giaccone M.D.

No participants were analyzed because only one participant went on study and he did not undergo the requisite lung cancer resection due to disease progression, which means there was insufficient tissue to perform all the secondary tumor marker analyses. There is no statistical power to draw any conclusions and thus the data are not informative.

Number of Participants With a Change in Ki-67 Due to the Effect of Pioglitazone in Tumor Tissue

Number of Participants With Effects of Pioglitazone on Multiple Biomarkers in Tumor

Number of Participants With Adverse Events

Number of Participants With Metabolic Activity Determined by Fludeoxyglucose Positron-emission Tomography (FDG-PET)

Number of Participants With Effects of Pioglitazone on Premalignant Tissue Biomarkers

Number of Participants With Effects of Pioglitazone on Histologically Normal Tissue Biomarkers

Number of Participants With Effects of Pioglitazone on Serum Tumor Markers

Overall Study

Antineoplastic Agents

Micronutrients

Hematinics

Vitamins

Paclitaxel

Albumin-Bound Paclitaxel

Carboplatin

Antibodies

Pemetrexed

Immunoglobulins

Tubulin Modulators

Antimitotic Agents

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Folinic Acid

Folate

Vitamin B9

Patients with nonsquamous NSCLC (including adenocarcinoma, large cell carcinoma and unspecified type) : sintilimab + pemetrexed + carboplatin; Patients with squamous NSCLC : sintilimab + albumin-bound paclitaxel + carboplatin; Followed by surgery within the 4th week after the second dose of sintilimab; Followed by 2 cycles of adjuvant chemotherapy, the researcher will decide whether to radiotherapy or not according to the clinical situation and pathological stage of the patient; Followed by the maintenance treatment of sintilimab for up to 1 year according to the requirements of patients.

Patients with nonsquamous NSCLC (including adenocarcinoma, large cell carcinoma and unspecified type) : sintilimab + pemetrexed + carboplatin; Patients with squamous NSCLC : sintilimab + albumin-bound paclitaxel + carboplatin; Followed by surgery within the 4th week after the third dose of sintilimab; Followed by 1 cycles of adjuvant chemotherapy, the researcher will decide whether to radiotherapy or not according to the clinical situation and pathological stage of the patient; Followed by the maintenance treatment of sintilimab for up to 1 year according to the requirements of patients.

200 mg by IV infusion every 3 weeks (Q3W), given on cycle day 1.

sintilimab

500 mg/m\^2 by IV infusion Q3W, given on cycle day 1.

pemetrexed

AUC 5 mg/mL/min by IV infusion Q3W, given on cycle day 1.

260 mg/m\^2 by IV infusion Q3W, given on cycle day 1.

albumin-bound paclitaxel

This is a Phase 2, prospective, randomized, open-Label, single-center international study that assesses the efficacy and safety of neoadjuvant therapy with different cycles of sintilimab combined with chemotherapy for resectable NSCLC. This trial will also explore the biomarkers of neoadjuvant immunochemotherapy.

This is a Phase 2, prospective, randomized, open-Label, single-center international study that assesses the efficacy and safety of neoadjuvant therapy with different cycles of sintilimab combined with chemotherapy for resectable NSCLC. In this trial, eligible subjects will be randomly assigned to arm A and arm B (1:1). Subjects in arm A will receive 2 cycles of neoadjuvant chemotherapy with sintilimab + chemotherapy and arm B will receive 3 cycles of neoadjuvant chemotherapy with sintilimab + chemotherapy, followed by surgery within the 4th week after the last dose of sintilimab. After operation, subjects in arm A will receive 2 cycles of adjuvant chemotherapy and arm B will receive 1 cycle of adjuvant chemotherapy, followed by the maintenance treatment of sintilimab for up to 1 year according to the requirements of patients. The primary purpose is MPR rate of neoadjuvant chemotherapy of resectable NSCLC with different cycles of sintilimab combined with platinum-based chemotherapy, which is defined as the percentage of participants having ≤10% viable tumor cells in the pathological examination of resected specimens.

Neoadjuvant of Sintilimab Combined With Chemotherapy for Resectable NSCLC（neoSCORE）

Neoadjuvant of Sintilimab Combined With Chemotherapy for Resectable NSCLC（neoSCORE）：A Prospective, Randomized, Open-Label, Single-Center Phase 2 Trial

MPR rate is defined as the percentage of participants having ≤10% viable tumor cells in the pathological examination of resected specimens.

pCR rate is defined as the percentage of participants lacking of evidence of viable tumor cells in the pathological examination of resected specimens.

ORR is defined as the percentage of participants having a complete response or a partial response, measured by RECIST 1.1.

2 years DFS rate is defined as the percentage of participants having no recurrence, distant metastasis or death within 2 years after operation.

2 years OS rate is defined as the percentage of participants having no death of any cause within 2 years after operation.The Kaplan-Meier estimator will be used to estimate median OS and its 95%CI and the survival curve.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pioglitazone to Treat Adults Undergoing Surgery for Non-small Cell Lung Cancer	NCT00923949	Non-Small-Cell ...	Pioglitazone	18 Years -	National Institutes of Health Clinical Center (CC)
Neoadjuvant of Sintilimab Combined With Chemotherapy for Resectable NSCLC（neoSCORE）	NCT04459611	Non-small Cell ...	sintilimab pemetrexed Carboplatin albumin-bound p...	18 Years - 75 Years	Second Affiliated Hospital, School of Medicine, Zhejiang University
Neoadjuvant of Sintilimab Combined With Chemotherapy for Resectable NSCLC（neoSCORE）	NCT04459611	Non-small Cell ...	sintilimab pemetrexed Carboplatin albumin-bound p...	18 Years - 75 Years	Second Affiliated Hospital, School of Medicine, Zhejiang University
Pioglitazone to Treat Adults Undergoing Surgery for Non-small Cell Lung Cancer	NCT00923949	Non-Small-Cell ...	Pioglitazone	18 Years -	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for resectable nsclc