Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Rare Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Adenocarcinoma

Adenocarcinoma of Lung

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Lung Adenocarcinoma

All Drugs and Chemicals

Antineoplastic Agents

Amino Acids

Tyrosine Kinase Inhibitors

Erlotinib Hydrochloride

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Patients receive Hsp90 inhibitor AUY922 IV over 1 hour once weekly and oral erlotinib hydrochloride once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

erlotinib hydrochloride

Hsp90 inhibitor AUY922

laboratory biomarker analysis

Undergo image-guided needle biopsy (correlative studies)

needle biopsy

mutation analysis

pharmacological study

Melissa Johnson

Hsp90 inhibitor AUY922 and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. This phase I/II trial is studying the side effects and best dose of Hsp90 inhibitor AUY922 when given together with erlotinib hydrochloride and to see how well it works in treating patients with stage IIIB-IV non-small cell lung cancer.

This is a phase I, dose-escalation study of Hsp90 inhibitor AUY922 followed by a phase II study. Patients receive Hsp90 inhibitor AUY922 IV over 1 hour once weekly and oral erlotinib hydrochloride once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.

Hsp90 Inhibitor AUY922 and Erlotinib Hydrochloride in Treating Patients With Stage IIIB-IV Non-Small Cell Lung Cancer

A Phase I/II Trial of Hsp 90 Inhibitor AUY-922 in Patients With Lung Adenocarcinoma With "Acquired Resistance" to EGFR Tyrosine Kinase Inhibitors

To determine the maximally tolerated dose (MTD), and recommended phase II dose of AUY922 when given in combination with erlotinib for patients with acquired resistance to erlotinib. (Phase I)

Escalation of dose will be in a 3+3 design. If no dose limiting toxicities (DLTs) are seen in 3 patients enrolled at that dose level, then dose will be escalated to the next dose level and the next 3 patients will be enrolled at that dose. Alternatively, if 1 DLT is seen in 3 patients at that dose level, 3 more patients will be added at that same dose level. If 1 DLT is seen in 6 patients at that dose level, MTD will be determined to be at that dose. If more than 1 DLT is seen at that dose level, then the prior lower dose level will be the considered the MTD.

DLT is defined as any of the following related to the investigational agent: Death and grade 3 and 4 specific hematological and non-hematological toxicities defined in the protocol.

Overall response rate (ORR) will be measured per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT scan or MRI:

Complete response (CR) defined as disappearance of all target lesions. Partial Response (PR), defined as \>=30% decrease in the sum of the longest diameter of target lesions.

Stable Disease (SD) defined as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study.

Progressive Disease (PD) defined as having at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions

To characterize the toxicity profile for the combination of erlotinib and AUY922.

Toxicity data will be collected every week for the first 28 day cycle and then every two weeks during treatment and up to 28 days after the last treatment. Adverse events will be graded according to the National Cancer Institute's Common Toxicity Criteria for adverse events version 4.0 (CTCAE v4.0). In general adverse events (AEs) will be graded according to the following:

Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE

Adverse events will be collected weekly for the first 28 day cycle and then every two weeks during treatment and up to 28 days after the last treatment. Adverse events will be graded according to the National Cancer Institute's Common Toxicity Criteria for adverse events version 4.0 (CTCAE v4.0). In general adverse events (AEs) will be graded according to the following:

Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE

Median Progression Free Survival (PFS) will be calculated from time of treatment initiation until the first documentation of progressive disease. Patients will be considered to have progressive disease when CT scan or MRI show at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Overall survival (OS) is defined as the time from treatment initiation until death due to any cause.

Overall Survival (OS) will be measured from treatment initiation until death due to any cause for patients with acquired resistance with T790M mutations in the phase II portion of the study.

Robert H. Lurie Cancer Center

Northwestern University

Only highest grade lab AEs were collected for each patient. All other AEs were collected as defined by clinicaltrials.gov. Phase I+II data collected together as toxicity objectives for the study were looking at AEs in relation to this combination of treatment rather than treatment dose.

Patients receive Hsp90 inhibitor AUY922 IV over 1 hour once weekly and 75mg oral erlotinib hydrochloride once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

erlotinib hydrochloride: Given orally

Hsp90 inhibitor AUY922: Given IV

laboratory biomarker analysis: Correlative studies

needle biopsy: Undergo image-guided needle biopsy (correlative studies)

mutation analysis: Correlative studies

pharmacological study: Correlative studies

Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib

Patients receive Hsp90 inhibitor AUY922 IV over 1 hour once weekly and oral erlotinib hydrochloride once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

erlotinib hydrochloride: Given orally

Hsp90 inhibitor AUY922: Given IV

laboratory biomarker analysis: Correlative studies

needle biopsy: Undergo image-guided needle biopsy (correlative studies)

mutation analysis: Correlative studies

pharmacological study: Correlative studies

Cohort 2 - 25 mg/m2AUY922+150 mg Daily Erlotinib

Cohort 3 - 37.5 mg/m2 AUY922+150 mg Daily Erlotinib

Cohort 4 - 55 mg/m2 AUY922+150 mg Daily Erlotinib

Cohort 5 - 70 mg/m2 AUY922+150 mg Daily Erlotinib

Phase II- 70 mg/m2 AUY922+150 mg Daily Erlotinib

Arm I

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Data was collected up until September 30 2014 when study was closed permanently and no further data was collected for patients survival due to IND withdrawal.

Clinical Trials Office

Maximally Tolerated Dose (MTD) of AUY922 and Erlotinib Treatment Combination (Phase I)

All patients that were treated at the MTD dose of 70mg/m2 AUG922 IV were evaluable for this outcome measure (This includes patients treated in cohort 5 of phase I and all patients treated in phase II of the study)

Overall Response Rate (ORR), Defined as Complete Response(CR) + Partial Response (PR) Using the Modified RECIST 1.1 Criteria for All Patients Treated at Dose of 70mg/m2 AUG922

Diarrhea

Skin rash

Hyperglycemia

Night blindness

Hypoalbuminemia

Fatigue

Elevated AST

Nausea

Hyponatremia

Elevated bilirubin

Elevated ALT

Myalgias/arthralgias

Visual complaints

Vomiting

Elevated APL

Decreased leukocytes

Hypokalemia

Pruritis/dry skin

Hypocalcemia

Anemia

Mucositis

Decreased lymphocytes

Decreased platelets

Hypomagnesemia

Decreased neutrophils

Toxicity collected from all patients treated at the MTD of 70mg/m2 AUY922. 6 patients in phase I and 19 patients in phase II were treated at this dose.

Toxicity as Assessed by NCI CTCAE Version 4.00 When AUG922 Administered at Its MTD (Phase I and II)

Elevated ALP

hypokalemia

anemia

Most frequent adverse events for patients treated with 25 to 55mg/m2 dose of AUY9222.

Incidence of Reported Adverse Events in Phase I

25 of the patients were treated at the MTD and were evaluable for progression free survival. Data was collected up until September 30 2014 when study was closed permanently and no further data was collected for patients survival due to IND withdrawal.

Progression-free Survival (Phase II)

Overall Survival (Phase II)

No data was collected or analyzed for this outcome measure. There is no data to report. IND was withdrawn before the studies anticipated termination date.

Overall Survival Among Patients With Acquired Resistance With T790M Mutations (Phase II)

Reached First Response at 4 Weeks

Confirmed Response at 8 Weeks

Continued Treatment After 8 Weeks

Survival Follow up for Two Years

Spots Global Cancer Trial Database for Hsp90 Inhibitor AUY922 and Erlotinib Hydrochloride in Treating Patients With Stage IIIB-IV Non-Small Cell Lung Cancer

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