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Adenocarcinoma of the LungPhase 1/2NCT01259089

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

A Phase 1/2 study testing erlotinib hydrochloride, Hsp90 inhibitor AUY922 and laboratory biomarker analysis in people with Adenocarcinoma of the Lung and Non-small Cell Lung Cancer, run by Northwestern University at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
erlotinib hydrochloride, Hsp90 inhibitor AUY922 and laboratory biomarker analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
38 participants
Where
2 sitesUnited States
Study dates
27 Apr 2011to 29 Sep 2014
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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)

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Northwestern University

    Chicago, Illinois, 60611

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
erlotinib hydrochloride, Hsp90 inhibitor AUY922, laboratory biomarker analysis, needle biopsy, mutation analysis
Keywords
Adenocarcinoma of the Lung, Non-small Cell Lung Cancer
Medical subject headings
Adenocarcinoma of Lung, Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • erlotinib hydrochlorideDrug

    Also called CP-358,774, erlotinib, OSI-774, Tarceva

    Given orally

  • Hsp90 inhibitor AUY922Drug

    Also called AUY922

    Given IV

  • laboratory biomarker analysisOther

    Correlative studies

  • needle biopsyProcedure or surgery

    Also called aspiration biopsy, puncture biopsy

    Undergo image-guided needle biopsy (correlative studies)

  • mutation analysisGenetic

    Correlative studies

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

Study groups in NCT01259089
Study groupRoleWhat they receive
Arm IExperimentalPatients 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.
Receives: Drug: erlotinib hydrochloride; Drug: Hsp90 inhibitor AUY922; Other: laboratory biomarker analysis; Procedure: needle biopsy; Genetic: mutation analysis; Other: pharmacological study

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    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.

    Measured: During the first 4 weeks of treatment for each patient.

  2. 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

    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

    Measured: At 8 weeks from treatment initiation

Secondary outcomes (5)

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

    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

    Measured: At weeks 1 through 4 and then every 2 weeks during treatment and 30 days post last treatment for up to 2 years and half years

  2. Incidence of Reported Adverse Events in Phase I

    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

    Measured: At weeks 1 through 4 and then every 2 weeks during treatment and 30 days post last treatment, for up to 2 years and half years

  3. Progression-free Survival (Phase II)

    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.

    Measured: From the time of first treatment with AUY922 to disease progression for up to 2 years post treatment

  4. Overall Survival (Phase II)

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

    Measured: From the time of first treatment with AUY922 to death, followed up to 2 years post treatment

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

    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.

    Measured: From the time of first treatment with AUY922 to death, followed for up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Dec 2010 (estimated)
  2. Study start27 Apr 2011
  3. Primary completion4 Jun 2013
  4. Study completion29 Sep 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
38 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01259089
Sponsor's protocol ID
NU 10L01
Other IDs
STU00038215
Status last verified
Oct 2018
First submitted
10 Dec 2010
Last updated
11 Sep 2019
Data monitoring committee
Yes

Publications

  • Johnson ML, Yu HA, Hart EM, Weitner BB, Rademaker AW, Patel JD, Kris MG, Riely GJ. Phase I/II Study of HSP90 Inhibitor AUY922 and Erlotinib for EGFR-Mutant Lung Cancer With Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors. J Clin Oncol. 2015 May 20;33(15):1666-73. doi: 10.1200/JCO.2014.59.7328. Epub 2015 Apr 13.

    PubMed 25870087

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing erlotinib hydrochloride, Hsp90 inhibitor AUY922 and laboratory biomarker analysis in people with Adenocarcinoma of the Lung and Non-small Cell Lung Cancer, run by Northwestern University at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximally Tolerated Dose (MTD) of AUY922 and Erlotinib Treatment Combination (Phase I) (time frame: During the first 4 weeks of treatment for each patient.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01259089, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Sep 2019.

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