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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Robert H. Lurie Cancer Center
Information provided by (Responsible Party):
Melissa Johnson, Northwestern University
ClinicalTrials.gov Identifier:
NCT01259089
First received: December 10, 2010
Last updated: June 3, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Adenocarcinoma of the Lung
Non-small Cell Lung Cancer
Drug: erlotinib hydrochloride
Drug: Hsp90 inhibitor AUY922
Other: laboratory biomarker analysis
Procedure: needle biopsy
Genetic: mutation analysis
Other: pharmacological study
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Trial of Hsp 90 Inhibitor AUY-922 in Patients With Lung Adenocarcinoma With "Acquired Resistance" to EGFR Tyrosine Kinase Inhibitors

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • Maximally tolerated dose (MTD) of AUY922 (Phase I) [ Time Frame: At weeks 1-4 and every 2 weeks thereafter ] [ Designated as safety issue: Yes ]
    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)

  • Overall response rate (ORR), defined as complete response(CR) + partial response (PR) using the modified RECIST 1.1 criteria (Phase II) [ Time Frame: At 8 weeks ] [ Designated as safety issue: No ]
    To measure progression-free survival and overall survival among patients treated with AUY922 and erlotinib. (Phase II)

  • Toxicity as assessed by NCI CTCAE version 4.02 (Phase I and II) [ Time Frame: At weeks 1-4 and every 2 weeks thereafter ] [ Designated as safety issue: Yes ]
    To characterize the toxicity profile for the combination of erlotinib and AUY922.


Secondary Outcome Measures:
  • Incidence of reported adverse events (Phase I) [ Time Frame: For 28 days following the last dose of study medication ] [ Designated as safety issue: Yes ]
  • Progression-free survival (Phase II) [ Time Frame: From the time of first treatment with AUY922 to disease progression ] [ Designated as safety issue: No ]
  • Overall survival (Phase II) [ Time Frame: From the time of first treatment with AUY922 to death ] [ Designated as safety issue: No ]
  • Overall survival among patients with acquired resistance with T790M mutations (Phase II) [ Time Frame: From the time of first treatment with AUY922 to death ] [ Designated as safety issue: No ]

Estimated Enrollment: 43
Study Start Date: March 2011
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
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.
Drug: erlotinib hydrochloride
Given orally
Other Names:
  • CP-358,774
  • erlotinib
  • OSI-774
  • Tarceva
Drug: Hsp90 inhibitor AUY922
Given IV
Other Name: AUY922
Other: laboratory biomarker analysis
Correlative studies
Procedure: needle biopsy
Undergo image-guided needle biopsy (correlative studies)
Other Names:
  • aspiration biopsy
  • puncture biopsy
Genetic: mutation analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • All patients must have pathologic evidence of advanced lung adenocarcinoma (stage IIIB or stage IV) confirmed histologically/cytologically at NU, MSKCC, or DFCI and EITHER previous RECIST-defined response (CR or PR) to an EGFR-TKI (erlotinib or gefitinib) or an investigational EGFR TK inhibitor OR a documented mutation in the EGFR gene (G719X, exon 19 deletion, L858R, L861Q)
  • Radiographic progression by RECIST during treatment with erlotinib/gefitinib
  • Received treatment with erlotinib/gefitinib throughout the one month prior to enrollment and at least six months at any time
  • Measurable (RECIST) indicator lesion not previously irradiated
  • Must have undergone a biopsy after the development of acquired resistance
  • Karnofsky Performance Status >= 70% OR ECOG/WHO Performance Status 0-1
  • Signed informed consent
  • Effective contraception and negative serum pregnancy test obtained within two weeks prior to the first administration of AUY922 in all pre-menopausal women (ie., last menstrual period =< 24 months ago) and women < 2 years after onset of menopause; menopause is defined as the time at which fertility ceases, where a woman has had no menstruation for > 24 months
  • Total bilirubin =< 1.5 x Upper Limit of Normal (ULN)
  • AST/SGOT and ALT/SGPT =< 3.0 x ULN, or =< 5.0 x ULN if liver metastasis present
  • Absolute neutrophil count (ANC) >= 1.5 x10^9/L
  • Hemoglobin (Hgb) >= 9g/dL
  • Platelets (plts) >= 100 x 10^9/L
  • Serum creatinine =< 1.5 x ULN or 24 hour clearance >= 50 mL/min

Exclusion Criteria:

  • Symptomatic CNS metastases which are symptomatic and /or requiring escalating doses of steroids
  • Prior treatment with any HSP90 inhibitor compounds
  • Conventional chemotherapy, radiation or monoclonal antibodies within 4 weeks (erlotinib/gefitinib therapy within the past 4 weeks IS allowed)
  • Palliative radiation within 2 weeks
  • Unresolved diarrhea >= CTCAE grade 2
  • Pregnant or lactating women
  • Women of childbearing potential (WCBP) (i.e. women able to become pregnant) not using double-barrier methods of contraception (abstinence, oral contraceptives, intrauterine device or barrier method of contraception in conjunction with spermicidal jelly, or surgically sterile); male patients whose partners are WCBP not using double-barrier methods of contraception
  • Acute or chronic liver or renal disease
  • Other concurrent severe and/or uncontrolled medical conditions that could cause unacceptable safety risks or compromise compliance with the protocol
  • Major surgery =< 2 weeks prior to randomization or who have not recovered from such therapy
  • History (or family history) of long QT syndrome
  • Mean QTc >= 450 msec on baseline ECG
  • History of clinically manifested ischemic heart disease =< 6 months prior to study start
  • History of heart failure or left ventricular (LV) dysfunction (LVEF =< 45%) by MUGA or ECG
  • Clinically significant resting bradycardia (< 50 beats per minute)
  • Clinically significant ECG abnormalities including 1 or more of the following: left bundle branch block (LBBB), right bundle branch block (RBBB) with left anterior hemi-block (LAHB); ST segment elevation or depression > 1mm, or 2nd (Mobitz II), or 3rd degree AV block
  • History ventricular tachycardia
  • Other clinically significant heart disease including congestive heart failure (New York Heart Association class III/IV) or uncontrolled hypertension (> 160/90 despite intensive medical management)
  • Patients who are currently receiving treatment with any medication which has a relative risk of prolonging the QTcF interval and cannot be switched or discontinued to an alternative drug prior to commencing AUY922
  • Known diagnosis of HIV infection (HIV testing is not mandatory)
  • Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention
  • Patients who are receiving warfarin (Coumadin®) will be excluded unless =< 2 mg/d, with an INR < 1.5
  • Patients with known disorders due to a deficiency in bilirubin glucuronidation (e.g. Gilbert's syndrome)
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01259089

Locations
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Northwestern University
Robert H. Lurie Cancer Center
Investigators
Principal Investigator: Melissa Johnson Northwestern University
  More Information

No publications provided

Responsible Party: Melissa Johnson, Principle Investigator, Northwestern University
ClinicalTrials.gov Identifier: NCT01259089     History of Changes
Other Study ID Numbers: NU 10L01, STU00038215
Study First Received: December 10, 2010
Last Updated: June 3, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Northwestern University:
Adenocarcinoma of the Lung
Non-small Cell Lung Cancer

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Adenocarcinoma
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
Erlotinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 01, 2014