Symptoms and General Pathology

All Conditions

Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Recurrence

Carcinoma

Adenocarcinoma

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Adenocarcinoma of Lung

Adenocarcinoma, Bronchiolo-Alveolar

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Lung Adenocarcinoma

Hypoglycemic Agents

All Drugs and Chemicals

Antineoplastic Agents

Metformin

Paclitaxel

Albumin-Bound Paclitaxel

Carboplatin

Tubulin Modulators

Antimitotic Agents

60 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin

Metformin plus 60 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin

Radiation therapy (RT) is given in 2 Gy fractions once daily 5 days per week to a total of 30 fractions and 60 Gy. Photons required; 3-dimensional conformal radiation therapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) permitted. Starts within 14 days of randomization (Chemoradiation arm) or 14 days after metformin starts (Chemoradiation + Metformin arm).

Radiation Therapy

2 AUC (area under the curve) via IV weekly on days 1, 8, 15, 22, 29, and 36 from start of radiation therapy. Two 21 day cycles of 6 AUC via IV starting 28-42 days after the end of radiation therapy.

Metformin is taken orally. Dose escalation begins 2 weeks prior to the initiation of chemoradiation. 500 mg twice daily days 1-7 of metformin. 500 mg three times daily days 8-14 of metformin. Three times a day with the following dosage: 500mg in the morning, 1000mg at noon, and 500mg in the evening concurrent with chemoradiation and through consolidation chemotherapy (days 15-126 of metformin),

50 mg/m2 via IV weekly on days 1, 8, 15, 22, 29, and 36 from start of radiation therapy. Two 21 day cycles of 200 mg/m2 via IV 28-42 days after the end of radiation therapy.

Theodoros Tsakiridis

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.

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.

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.

Chemotherapy and Radiation Therapy With or Without Metformin Hydrochloride in Treating Patients With Stage III Non-small Cell Lung Cancer

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

Progression is defined per RECIST v1.1 as change in a known lesion(s) meeting one of the following criteria: \[1\] At least a 20% increase in the sum of the longest diameter of target lesions such that the absolute increase must be \> 5 mm. \[2\] Appearance of ≥1 new lesions. Progression-free survival time is defined as time from randomization to the date of first progression, death, or last known follow-up (censored). Progression-free survival rates are estimated using the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. One-year rates are provided. Analysis occurred after 102 progression-free survival events were reported.

Overall survival time is defined as time from randomization to the date of death from any cause or last known follow-up (censored). Overall survival rates are estimated using the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. One-year rates are provided. Analysis occurred after 102 progression-free survival events were reported.

Local-regional progression (LRP) is defined as progression within the planned treatment volume (PTV) or outside the PTV but within the same lobe(s) of the lung as the primary tumor or in regional lymph nodes. Progression is defined as change in a known lesion(s) meeting one of the following criteria: \[1\] ≥ 20% increase in the sum of the longest diameter of target lesions such that the absolute increase must be \> 5 mm. \[2\] Appearance of ≥1 new lesions. LRP time is defined as time from randomization to the date of first LRP, death without LRP (competing risk), or last known follow-up (censored). LRP rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. One-year rates are provided. Analysis occurred after 102 LRP events were reported.

Distant metastasis (DM) is defined as the appearance of ≥ 1 new lesions at any site (including pleural or pericardial effusion) outside of the following: the planned treatment volume, the same lobe(s) of the lung as the primary tumor, or regional lymph nodes. Time to DM is defined as time from randomization to the date of first DM, death without DM (competing risk), or last known follow-up (censored). DM rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. One-year rates are provided. Analysis occurred after 102 progression-free survival events were reported.

Adverse events (AE) were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to adverse event. "Treatment-related" is defined definitely, probably, or possibly related to treatment.

National Cancer Institute (NCI)

NRG Oncology

Chemoradiation

Metformin + Chemoradiation

Total

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

0 = Asymptomatic; 1 = Symptomatic but completely ambulatory; 2 = Symptomatic, \<50% in bed during the day; 3 = Symptomatic, \>50% in bed, but not bed bound; 4 = Bedbound; 5 = Death

Zubrod performance status

Tumor stage refers to the size and/or extent of the main tumor. The higher the number after the T, the larger the tumor or the more it has grown into nearby tissues. T's may be further divided to provide more detail, such as T3a and T3b.TX=Primary tumor not visualized by imaging or bronchoscopy. Regional lymph nodes staging refers to the number and/or extent of spread of lymph nodes that contain cancer. The higher the number after the N, the greater the involvement of regional lymph nodes. M0=No distant metastasis

American Joint Committee on Cancer (AJCC ) Stage, 7th edition

Histology

Did the patient use cigarettes?

Wendy Seiferheld

The study was powered to detect an improvement of the 1-year progression-free survival rate from 50% (no metformin) to 65% (metformin) or equivalently a hazard ratio (HR) of 0.622, at one-sided type 1 error of 0.1 and 85% power with at least 102 progression-free survival events.

Percentage of Participants Alive Without Progression (Progression-free Survival)

Percentage of Participants Alive (Overall Survival)

Percentage of Participants With Local-regional Progression

Percentage of Participants With Distant Metastases

Eligible participants who started protocol treatment

Percentage of Participants With Treatment-related Grade 3 or Higher Adverse Events

Overall Study

Amino Acids

Erlotinib Hydrochloride

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Patients receive Akt inhibitor MK2206 PO QOD of a 28-day course, and erlotinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Akt Inhibitor MK2206

Laboratory Biomarker Analysis

Pharmacological Study

Primo Lara

This phase II trial studies the side effects and how well Akt inhibitor MK2206 (MK2206) and erlotinib hydrochloride works in treating patients with advanced non-small cell lung cancer who have progressed after previous response to erlotinib hydrochloride therapy. MK2206 and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To evaluate the efficacy (with the primary endpoint of disease control at 12 weeks) and tolerability of the combination of MK2206 plus erlotinib (erlotinib hydrochloride) in previously erlotinib-treated patients with recurrent or progressive advanced non-small cell lung cancer (NSCLC) whose tumors are either epidermal growth factor receptor (EGFR) mutated or EGFR wild-type.

SECONDARY OBJECTIVES:

I. To determine progression-free survival of previously erlotinib-treated patients with NSCLC who are treated with MK2206 plus erlotinib. II. To determine the overall survival of previously erlotinib-treated patients with NSCLC who are treated with MK2206 plus erlotinib.

III. To assess the toxicity experienced by previously erlotinib-treated patients with NSCLC treated with MK2206 plus erlotinib. IV. To perform correlative analysis of tumor biomarkers to assess, in a preliminary manner, the association between tumor mutations and/or abnormalities and clinical outcome of previously erlotinib-treated patients with NSCLC treated with MK2206 plus erlotinib.

OUTLINE:

Patients receive Akt inhibitor MK2206 orally (PO) every other day (QOD) of a 28-day course, and erlotinib hydrochloride PO once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up every 12 weeks for one year and then annually thereafter.

MK2206 and Erlotinib Hydrochloride in Treating Patients With Advanced Non-Small Cell Lung Cancer Who Have Progressed After Previous Response to Erlotinib Hydrochloride Therapy

Phase II Trial of the Akt Inhibitor MK-2206 Plus Erlotinib (OSI-774) in Patients With Advanced Non-small Cell Lung Cancer Who Have Progressed After Previous Response (Including Stable Disease) With Erlotinib Therapy

Disease-control rate defined as response rate + stable disease at 12 weeks. Stable disease must have been achieved for 12 weeks or longer. Response evaluated per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Objective Response = CR + PR

Estimated using the product-limit method of Kaplan and Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Toxicities of Grade 3 or higher Attributed to Akt inhibitor MK2206 plus erlotinib hydrochloride, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

Estimated using the product-limit method of Kaplan and Meier. Event defined as death due to any cause.

Includes all adverse events regardless of attribution and grade.

EGFR-Mutated Tumors

EGFR Wild-Type Tumors

Age, Continuous

United States

Region of Enrollment

DCC Project Administrator

Disease-control Rate

Objective Response

Median Progression-free Survival

Anemia

Diarrhea

Mucositis

Nausea

Vomiting

Fatigue

Skin infection

Lung infection

Urinary tract infection

Creatinine increased

Lymphocyte count decreased

Anorexia

Dehydration

Hyperglycemia

Hypokalemia

Hyponatremia

Hypophophatemia

Myalgia

Neoplasm

Dyspnea

Dry skin

Erythema multiforme

Skin peeling (feet)

Pruritus

Rash

Hypertension

Toxicity of Akt Inhibitor MK2206 Plus Erlotinib Hydrochloride

Median Overall Survival

Disease Attributes

Micronutrients

Hematinics

Vitamins

Pemetrexed

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Glutamic Acid

Folinic Acid

Folate

Vitamin B9

Patients receive pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients receive pemetrexed disodium IV as in Arm A and erlotinib hydrochloride PO QD on days 2-17. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Pemetrexed Disodium

Roman Perez-Soler

This randomized phase II trial studies how well pemetrexed disodium with or without erlotinib hydrochloride works in treating patients with stage IIIB-IV or recurrent non-small cell lung cancer. Drugs used in chemotherapy, such as pemetrexed disodium, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether pemetrexed disodium is more effective with or without erlotinib hydrochloride in treating non-small cell lung cancer.

PRIMARY OBJECTIVES:

I. To evaluate progression free survival (PFS) in the schedule-modulated concomitant administration of erlotinib (erlotinib hydrochloride) and pemetrexed (pemetrexed disodium), and in single agent pemetrexed in patients with advanced non-small cell lung cancer (NSCLC) as second-line chemotherapy.

SECONDARY OBJECTIVES:

I. To evaluate antitumor objective response rate (complete response \[CR\] + partial response \[PR\]) per Response Evaluation Criteria in Solid Tumors (RECIST) criteria.

II. To evaluate disease control rate (response rate + stable disease, i.e., CR+PR+ stable disease \[SD\]) and duration of response.

III. To evaluate median time to progression (TTP) and overall survival (OS). IV. To evaluate the safety profile of concurrent pemetrexed and erlotinib versus single agent pemetrexed.

TERTIARY OBJECTIVES:

i. To determine several molecular and cellular biomarkers in the tumors, the skin and the serum that are predictive of the efficacy of pemetrexed and erlotinib.

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

ARM A: Patients receive pemetrexed disodium intravenously (IV) over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive pemetrexed disodium IV as in Arm A and erlotinib hydrochloride orally (PO) once daily (QD) on days 2-17. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 12 months.

Pemetrexed Disodium With or Without Erlotinib Hydrochloride in Treating Patients With Stage IIIB-IV or Recurrent Non-Small Cell Lung Cancer

A Randomized Phase II Study of Schedule-Modulated Concomitant Pemetrexed (Alimta) and Erlotinib (Tarceva) vs Single Agent Pemetrexed (Alimta®) in Patients With Progressive or Recurrent Non-small Cell Lung Cancer (NSCLC)

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Response rates in each arm will be summarized by computing proportions and corresponding 95% confidence intervals.

Time to event endpoints will be analyzed using standard survival analytic methods, including the Kaplan-Meier approach for estimating the survival distributions.

Eli Lilly and Company

OSI Pharmaceuticals

Albert Einstein College of Medicine

Principal Investigator

Patients receive pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis: Correlative studies

Pemetrexed Disodium: Given IV

Arm A (Pemetrexed)

Patients receive pemetrexed disodium IV as in Arm A and erlotinib hydrochloride PO QD on days 2-17. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Erlotinib Hydrochloride: Given PO

Laboratory Biomarker Analysis: Correlative studies

Pemetrexed Disodium: Given IV

Arm B (Pemetrexed Disodium, Erlotinib Hydrochloride)

White

Black

Hispanic

Asian

Race/Ethnicity, Customized

<=15 pack-years

>15 pack-years

Smoking history

ECOG PS 0

ECOG PS 1/2

ECOG PERFORMANCE STATUS:

0- Fully active, able to carry on all pre-disease performance without restriction

1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature
2. Ambulatory and capable of all selfcare but unable to carry out any work activities

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Chemotherapy and Radiation Therapy With or Without Metformin Hydrochloride in Treating Patients With Stage III Non-small Cell Lung Cancer	NCT02186847	Adenosquamous L... Bronchioloalveo... Large Cell Lung... Lung Adenocarci... Non-Small Cell ... Recurrent Non-S... Squamous Cell L... Stage IIIA Non-... Stage IIIB Non-...	Radiation Thera... Carboplatin Metformin Paclitaxel	18 Years -	NRG Oncology
MK2206 and Erlotinib Hydrochloride in Treating Patients With Advanced Non-Small Cell Lung Cancer Who Have Progressed After Previous Response to Erlotinib Hydrochloride Therapy	NCT01294306	Adenosquamous L... Bronchioloalveo... Large Cell Lung... Lung Adenocarci... Recurrent Non-S... Squamous Cell L...	Akt Inhibitor M... Erlotinib Hydro... Laboratory Biom... Pharmacological...	18 Years -	National Cancer Institute (NCI)
Pemetrexed Disodium With or Without Erlotinib Hydrochloride in Treating Patients With Stage IIIB-IV or Recurrent Non-Small Cell Lung Cancer	NCT00950365	Bronchioloalveo... Large Cell Lung... Lung Adenocarci... Recurrent Non-S... Stage IIIB Non-... Stage IV Non-Sm...	Erlotinib Hydro... Laboratory Biom... Pemetrexed Diso...	18 Years -	Albert Einstein College of Medicine

Spots Global Cancer Trial Database for bronchioloalveolar carcinoma