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Recurrent Non-small Cell Lung CancerPhase 1NCT01784640

Pemetrexed Disodium and Hsp90 Inhibitor AUY922 in Treating Patients With Previously Treated Stage IV Non-Small Cell Lung Cancer

A Phase 1 study testing Hsp90 inhibitor AUY922, pemetrexed disodium and pharmacological study in people with Recurrent Non-small Cell Lung Cancer and Squamous Cell Lung Cancer, run by Jonsson Comprehensive Cancer Center at 1 site 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

This phase I trial studies the side effects and the best dose of Hsp90 inhibitor AUY922 when given together with pemetrexed disodium in treating patients with previously treated stage IV non-small cell lung cancer. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Hsp90 inhibitor AUY922, pemetrexed disodium and pharmacological study
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
1 siteUnited States
Study dates
31 Jan 2014to 11 Oct 2018
Phase
Phase 1
Are there results?
None posted in the registry

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

  • Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations
  • Histologically- or cytologically-confirmed stage IV non-squamous, NSCLC who have progressed after at least one prior line of treatment; in the expansion phase, participants are only eligible if their molecular category has not been fully enrolled (10 participants with epidermal growth factor receptor (EGFR) mutations, 5 participants with anaplastic lymphoma receptor tyrosine kinase (ALK) gene rearrangement, 5 participants with wild type v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), EGFR and ALK)
  • At least one measurable lesion as defined by modified RECIST version 1.1; previously irradiated lesions are not measurable unless the lesion is new or has demonstrated clear progression after radiation
  • Last chemotherapy or treatment with another systemic anti-cancer agent must have stopped >= 4 weeks prior to enrollment (or >= 5 half-lives for oral tyrosine-kinase inhibitors or 2 weeks for palliative radiotherapy); participants must have recovered (Common Terminology Criteria for Adverse Events [CTCAE] =< 1 or baseline) from acute toxicities of any previous therapy (with the exception of alopecia)
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Expected survival time of >= 3 months in the opinion of the investigator
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  • Absolute neutrophil count (ANC) >=1.5 x 10^9/L
  • Hemoglobin (Hgb) >= 9 g/dl
  • Platelets (plt) >= 100 x 10^9/L
  • Potassium within normal limits
  • Total calcium (corrected for serum albumin) within normal limits or corrected with supplements
  • Magnesium within lower limits or corrected with supplements
  • Phosphorus within lower limits or corrected with supplements
  • Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) =< 1.5 x upper limit of normal (ULN)
  • AST/SGOT and ALT/SGPT =< 2.5 x upper limit of normal (ULN) if liver metastases are present
  • Serum bilirubin =< 1.5 x ULN
  • Serum creatinine =< 1.5 x ULN or 24-hour clearance >= 50 ml/min
  • Negative serum or urine pregnancy test; the serum pregnancy test must be obtained prior to the first administration of AUY922 (=< 14 days prior to dosing) in all pre-menopausal women and women < 2 years after the onset of menopause
  • Ability to provide a formalin-fixed, paraffin-embedded (FFPE) tumor tissue sample containing representative tumor tissue from a previously obtained biopsy/resection that meets specific tissue sample requirements at screening

Who cannot join

  • Unresolved diarrhea >= CTCAE (v4.0) grade 1
  • Pregnant or lactating women
  • Fertile women of childbearing potential (WCBP) not using (or refusing to use) adequate methods of contraception as agreed on between her and the consenting investigator; male participants not using (or refusing to use) a condom during intercourse
  • History of another primary cancer within 3 years prior to enrollment with the exception of curatively treated skin cancer (other than melanoma) or curatively treated cervical carcinoma in-situ
  • History of central nervous system (CNS) metastasis; Note: participants without clinical signs and symptoms of CNS involvement are not required to have magnetic resonance imaging (MRI) of the brain; (exception: participants with treated brain metastases who are asymptomatic, not currently on steroid therapy, and clinically stable for >= 2 weeks will be eligible for protocol participation)
  • Prior treatment with pemetrexed
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  • Prior anti-neoplastic treatment with any heat shock protein 90 (HSP90) or histone deacetylase (HDAC) inhibitor compound
  • Participants who have undergone any major surgery =< 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
  • Last chemotherapy or treatment with another systemic anti-cancer agent must have stopped >= 4 weeks prior to enrollment (or >= 5 half-lives for oral tyrosine-kinase inhibitors); participants with EGFR mutations and ALK gene rearrangement who have not received a tyrosine kinase inhibitor targeting their molecular abnormality (e.g., erlotinib or crizotinib respectively); participants must have recovered (CTCAE =< 1) from acute toxicities of any previous therapy (with the exception of alopecia)
  • Participants who have concurrent or uncontrolled illness that the investigator feels will impede study participation including, but not limited to:
  • Acute or chronic liver disease
  • Acute or chronic renal disease
  • Active or ongoing infection
  • Psychiatric illness/social situations that would limit compliance with study requirements
  • Participants with known disorders due to a deficiency in bilirubin glucuronidation (e.g. Gilbert's syndrome)
  • Intolerance of Vitamin B12, folic acid or dexamethasone
  • Participants with following cardiac criteria:
  • History of long QT syndrome
  • QTcF >= 450 ms during screening electrocardiogram (ECG)
  • History of clinically manifest ischemic heart disease including myocardial infarction, stable or unstable angina pectoris, coronary arteriography or cardiac stress testing/imaging with findings consistent with infarction or clinically significant coronary occlusion ≤ 6 months prior to study start
  • History of heart failure or left ventricular (LV) dysfunction (LV ejection fraction [EF] =< 45%) by multi gated acquisition scan (MUGA) or echocardiogram (ECHO)
  • Clinically significant ECG abnormalities including one or more of the following: left bundle branch block (LBBB), right bundle branch block (RBBB) with left anterior hemiblock (LAHB); ST segment elevations or depressions > 1mm, or 2nd (Mobitz II) or 3rd degree atrioventricular block (AV) block
  • History and presence of atrial fibrillation, atrial flutter or ventricular arrhythmias including ventricular tachycardia or Torsades de pointes
  • Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with a hypertensive regimen)
  • Clinically significant resting bradycardia (< 50 beats per minute)
  • Participants who are currently receiving treatment with any medication which has a relative risk or prolonging the QTcF interval or inducing Torsades de pointes (as listed in protocol) and cannot be switched or discontinued to an alternative drug prior to commencing AUY922 dosing
  • Participants who are on a cardiac pacemaker
  • Participants unwilling or unable to comply with the protocol
  • Participants known to be human immunodeficiency virus (HIV) positive; testing is not required in the absence of clinical signs and symptoms suggesting HIV infection
  • Any systemic anti-cancer treatment out of allowed timelines
  • Concurrent cytotoxic or immunosuppressive therapy for non-malignant disease (e.g., for rheumatoid arthritis or lupus)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Jonsson Comprehensive Cancer Center

    Los Angeles, California, 90095

Other trials in United States

About this study

Official title: A Phase IB Dose-Escalation Study of Pemetrexed and AUY922 in Previously-Treated Patients With Metastatic Non-Squamous, Non-Small Cell Lung Cancer

This phase I trial studies the side effects and the best dose of Hsp90 inhibitor AUY922 when given together with pemetrexed disodium in treating patients with previously treated stage IV non-small cell lung cancer. Hsp90 inhibitor AUY922 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as pemetrexed disodium, work in different ways to stop the growth of tumor cell, either by killing the cells or stopping them from dividing. Giving Hsp90 inhibitor AUY922 together with pemetrexed disodium may kill more tumor cells

Read the detailed description

PRIMARY OBJECTIVES:

  1. Evaluate the safety and tolerability of escalating doses of AUY922 (Hsp90 inhibitor AUY922) when given with pemetrexed (pemetrexed disodium) 500 mg/m^2 in participants with previously-treated stage IV non-squamous, non-small cell lung cancer (NSCLC).

SECONDARY OBJECTIVES:

  1. Determine the objective tumor response rate as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria in participants with previously treated non-squamous NSCLC treated with pemetrexed and AUY922.

II. Evaluate the pharmacokinetic profile of pemetrexed and AUY922. III. Evaluate toxicity, including visual toxicity, in participants treated with AUY922 and pemetrexed.

IV. Analyze tumor-tissue biomarkers for potential correlation with response.

OUTLINE: This is a dose-escalation study of Hsp90 inhibitor AUY922.

Patients receive Hsp90 inhibitor AUY922 intravenously (IV) over 60 minutes weekly and pemetrexed disodium IV over 15 minutes every 3 weeks. Courses repeat every 21 days for 6 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days.

Being tested
Hsp90 inhibitor AUY922, pemetrexed disodium, pharmacological study, laboratory biomarker analysis
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

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

  • Hsp90 inhibitor AUY922Drug

    Also called AUY922

    Given IV

  • pemetrexed disodiumDrug

    Also called ALIMTA, LY231514, MTA

    Given IV

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT01784640
Study groupRoleWhat they receive
Treatment (Hsp90 inhibitor AUY922, pemetrexed disodium)ExperimentalPatients receive Hsp90 inhibitor AUY922 IV over 60 minutes weekly and pemetrexed disodium IV over 15 minutes every 3 weeks. Courses repeat every 21 days for 6 months in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Hsp90 inhibitor AUY922; Drug: pemetrexed disodium; Other: pharmacological study; Other: laboratory biomarker analysis

What is being measured

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

  1. Incidence of adverse events (AEs) as assessed by National Cancer Institute (NCI) CTCAE version 4.0

    Safety will be assessed through tabulation, grading and attribution of serious adverse events (SAEs) and AEs.

    Measured: Up to 30 days after completion of study treatment

Secondary outcomes (1)

  1. Tumor response rate according to RECIST version 1.1

    The proportion of ever achieving a clinical response will be estimated and constructed with an exact one-sided 90% confidence interval to identify the likely range for the underlying tumor response rate. Clinical response will be correlated with biomarkers using a variety of analytic techniques.

    Measured: Up to 30 days after completion of study treatment

Timeline

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

  1. First posted6 Feb 2013 (estimated)
  2. Study start31 Jan 2014
  3. Primary completion11 Oct 2018
  4. Study completion11 Oct 2018

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01784640
Sponsor's protocol ID
12-001489
Other IDs
NCI-2013-00410, L-05
Status last verified
Apr 2018
First submitted
5 Feb 2013
Last updated
3 Sep 2020
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Hsp90 inhibitor AUY922, pemetrexed disodium and pharmacological study in people with Recurrent Non-small Cell Lung Cancer and Squamous Cell Lung Cancer, run by Jonsson Comprehensive Cancer Center at 1 site 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 19 inclusion and 31 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 3 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 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.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Incidence of adverse events (AEs) as assessed by National Cancer Institute (NCI) CTCAE version 4.0 (time frame: Up to 30 days after completion of study treatment). 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 NCT01784640.

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 3 Sep 2020.

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