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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

December 10, 2010
June 3, 2014
March 2011
December 2015   (final data collection date for primary outcome measure)
  • 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.
  • Maximally tolerated dose (MTD) of AUY922 (Phase I) [ Time Frame: At weeks 1-4 and every 2 weeks thereafter ] [ Designated as safety issue: Yes ]
  • Overall response rate (ORR), defined as (CR+PR) using the modified RECIST 1.1 criteria (Phase II) [ Time Frame: At 8 weeks ] [ Designated as safety issue: No ]
  • 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 ]
Complete list of historical versions of study NCT01259089 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
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

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.

Interventional
Phase 1
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Adenocarcinoma of the Lung
  • Non-small Cell Lung Cancer
  • 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
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.
Interventions:
  • Drug: erlotinib hydrochloride
  • Drug: Hsp90 inhibitor AUY922
  • Other: laboratory biomarker analysis
  • Procedure: needle biopsy
  • Genetic: mutation analysis
  • Other: pharmacological study
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
43
December 2016
December 2015   (final data collection date for primary outcome measure)

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)
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01259089
NU 10L01, STU00038215
Yes
Melissa Johnson, Northwestern University
Northwestern University
Robert H. Lurie Cancer Center
Principal Investigator: Melissa Johnson Northwestern University
Northwestern University
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP