Non Small Cell Lung CancerPhase 2NCT01854034
Phase 2 Study of AUY922 in NSCLC Patients With Exon 20 Insertion Mutations in EGFR
A Phase 2 study testing AUY922 in people with Non Small Cell Lung Cancer, run by Massachusetts General Hospital at 4 sites in United States.
Trial summary
This research study is a Phase II clinical trial, which tests the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific cancer. "Investigational" means that the drug is being studied. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non Small Cell Lung Cancer
- What is being tested?
- AUY922
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 4 sitesUnited States
- Study dates
- Jul 2013to Mar 2017
- Phase
- Phase 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
- Histologically or cytologically confirmed stage IV or recurrent NSCLC
- Measurable disease by RECIST 1.0
- Must have received at least one prior line of therapy for advanced lung cancer (no maximum number)
- Life expectancy of at least 12 weeks
Who cannot join
- Pregnant or breastfeeding
- Radiation within 2 weeks
- Cytotoxic chemotherapy or monoclonal antibodies within 4 weeks
- EGFR tyrosine kinase inhibitor within 2 weeks
- Other small molecule inhibitor within 2 weeks
- Experimental treatment within 30 days
Show all 21Show fewer
- Prior treatment with any HSP90 or HDAC inhibitor compound
- Known and untreated brain metastases
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to AUY922
- Unresolved diarrhea greater than or equal to CTCAE version 4, grade 1
- Major surgery within 2 weeks of starting study drug or have not recovered from side effects of surgery
- Known disorders due to a deficiency in bilirubin glucuronidation
- Requiring use of therapeutic doses of warfarin (Coumadin)
- History of long QT syndrome
- History of clinically manifest ischemic heart disease, heart failure or left ventricular dysfunction
- Clinically significant ECG abnormalities
- Other clinically significant heart disease
- Currently receiving treatment with any medication which has a relative risk of prolonging the QTc interval or inducing Torsades de Pointes
- On a cardiac pacemaker
- Concurrent malignancies or invasive cancers diagnosed within 3 years except for adequately treated basal cell cancer of the skin or in situ cancer of the cervix
- Known to be HIV positive
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Brigham and Women's Hospital
Boston, Massachusetts, 02215
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
About this study
Official title: Phase II Study of AUY922 in NSCLC Patients With Exon 20 Insertion Mutations in EGFR
This research study is a Phase II clinical trial, which tests the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific cancer. "Investigational" means that the drug is being studied. It also means that the FDA has not yet approved the drug for your type of cancer or for any use outside of research studies.
It has been found that some people with NSCLC have a change (mutation) in a certain gene called the EGFR gene. This mutated gene helps cancer cells grow. The majority of NSCLC patients with EGFR mutations achieve good outcomes with erlotinib or other EGFR inhibitor therapies, with a high response rate, prolonged progression-free survival and possibly improved overall survival from therapy. However, the 4% of EGFR mutant patients that harbor an exon 20 insertion mutation historically have reaped little benefit from EGFR-directed therapy due to the low affinity of this mutation for direct EGFR inhibitors, especially erlotinib and gefitinib (see Yasuda et al, Lancet Oncol 2011). This group of patients is ideal for studying other targeted therapeutic strategies that could affect the oncogene mutation in EGFR via alternative mechanisms.
Read more
AUY922 is an investigational drug that may stop cancer cells from growing abnormally. This drug has been used in other research studies. Information from those other research studies suggests that AUY922 may be effective in killing cancer cells in patients with exon 20 insertion mutations in EGFR.
The purpose of this study is to test the safety of AUY922 and determine how well AUY922 works for participants with advanced NSCLC and exon 20 insertion mutations in EGFR.
Read the detailed description
Interested patients will be asked to undergo some screening tests and procedures to confirm that they are eligible. Many of these tests and procedures are likely to be part of regular cancer care and may be done even if it turns out that patients do not take part in the research study. If patients have had some of these tests or procedures recently, they may or may not have to be repeated. These tests and procedures include: a medical history physical exam, performance status, assessment of tumor, EKG, electrocardiogram or multigated acquisition scan, eye exam, blood draw, blood pregnancy test, urine test and collection of a piece of the stored tumor tissue.
The study treatment is given in 21 day cycles. AUY922 is given by IV (into a vein). This is called an infusion. Patients will receive an infusion of AUY922 on days 1, 8 and 15 of each cycle (once per week). The infusion will take about 60 minutes.
A schedule of clinic visits for the study is summarized below.
Cycle 1, Day 1: physical exam, including measurement of vital signs and weight; performance status; EKG; blood draw; routine urine test Cycle 1, Day 2: EKG Cycle 1, Day 3: EKG Cycle 1, Day 8: Vital signs, performance status, EKG, questions about side effects and other medications taken Cycle 1, Day 15: Physical exam, including measurement of vital signs, performance status; EKG; blood draw; questions about side effects and other medications taken Note that in Cycle 1 patients will need to stay at (or return to) the clinic for the last EKG following the Day 1 AUY922 infusion, and come to the clinic on Days 2 and 3 for EKGs.
Cycle 2 and beyond, Day 1: physical exam, including measurement of vital signs and weight; performance status; EKG; blood draw; questions about side effects and other medications taken; routine urine test Cycle 2 and beyond, Day 8: Vital signs; performance status; EKG; questions about side effects and other medications taken Cycle 2 and beyond, Day 15: Physical exam, including measurement of vital signs; performance status; EKG; blood draw; questions about side effects and other medications taken.
Additional EKGs may be done at any time if the study doctor thinks it is necessary. A blood test to measure the amount of cardiac enzymes in the blood may be done whenever abnormal findings are suspected or seen on the EKG.
Additional tests and procedures:
- CT or MRI scans will be done to measure the disease about every 6 weeks.
- A blood pregnancy test, for women who can become pregnant, will be performed every 6 weeks or at any point in which pregnancy is suspected.
- A standard eye exam will be done on Cycle 3, Day 1. Additional eye exams will be done if patients experience any eye-related symptoms, such as changes in vision.
Within 1 week after the last dose of the study drug AUY922, patients will be asked to return to the clinic. At this visit the following will be done: physical examination, performance status, EKG, ECHO or MUGA scan, blood draw, urine test, eye exam, questions about side effects and other medications taken. Patients will be asked to return to the clinic a second time so investigators can follow-up on any ongoing side effects after stopping AUY922.
- Conditions
- Non Small Cell Lung Cancer
- Being tested
- AUY922
- Keywords
- Advanced disease, EGFR mutation
- 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.
AUY922Drug
AUY922 administered intravenously once a week at 70mg/m2
| Study group | Role | What they receive |
|---|---|---|
| AUY922 Treatment Arm | Experimental | AUY922 administered once weekly via intravenous, 70 mg/m2 Receives: Drug: AUY922 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate
The number of participants that achieved a response to treatment as assessed by Response Evaluation Criteria is Solid Tumors (RECIST). Response is defined as having achieved either a complete response (CR) or a partial response (PR).
- Complete Response (CR): Disappearance of all target lesions. Any pathological lymph node must have reduction in short axis to < 10 mm.
- Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Measured: From the start of treatment until the time of disease progression, median duration of follow-up of about 3 months
Secondary outcomes (3)
Median Progression Free and Overall Survival
Overall survival (OS) is measured from the start of treatment until the time of death. Progression free survival is measured from the start of treatment until the time of death or disease progression as assessed by RECIST. Progressive disease is defined as having at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study with at least a 5 mm absolute increase in the sum of all lesions. The appearance of one or more new lesions denotes disease progression.
Measured: From the start of treatment until the time or death or disease progression
The Number of Participants With Treatment Related Serious Adverse Events
The number of participants with serious adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) that were deemed to be possibly, probably, or definitely related to study treatment as determined by the treating physician.
Measured: From the start of treatment until 28 days after the end of treatment
Exon 20 EGFR Mutations Among Participants That Responded to Treatment
The specific exon 20 epidermal growth factor receptor (EGFR) mutations among participants that achieved either a partial response or complete response as assessed by RECIST. The EGFR mutations were assessed from biopsies taken at baseline and then the baseline mutations were categorized by disease response.
- Complete Response (CR): Disappearance of all target lesions. Any pathological lymph node must have reduction in short axis to < 10 mm.
- Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Measured: Baseline, at the time of response
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2013 (estimated)
- Study startJul 2013
- Primary completionMar 2017
- Study completionMar 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lecia V. Sequist, Massachusetts General Hospital
- Investigators
- Lecia Sequist, MD, MPH, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01854034
- Sponsor's protocol ID
- 12-484
- Status last verified
- Mar 2018
- First submitted
- 12 May 2013
- Last updated
- 10 Apr 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Piotrowska Z, Costa DB, Oxnard GR, Huberman M, Gainor JF, Lennes IT, Muzikansky A, Shaw AT, Azzoli CG, Heist RS, Sequist LV. Activity of the Hsp90 inhibitor luminespib among non-small-cell lung cancers harboring EGFR exon 20 insertions. Ann Oncol. 2018 Oct 1;29(10):2092-2097. doi: 10.1093/annonc/mdy336.
PubMed 30351341
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of AUY922 in NSCLC Patients With Exon 20 Insertion Mutations in EGFR
- ClinicalTrials.gov ID
- NCT01854034
- Acronym / sponsor ID
- 12-484
- Conditions
- Non Small Cell Lung Cancer
- Keywords
- Advanced disease, EGFR mutation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- Jul 2013
- Primary completion
- Mar 2017 (actual)
- Study completion
- Mar 2017 (actual)
- First posted
- 15 May 2013 (estimated)
- Results
- Posted 10 Apr 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research study is a Phase II clinical trial, which tests the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific cancer. "Investigational" means that the drug is being studied. It also means that the FDA has not yet approved the drug for your type of cancer or for any use outside of research studies.
It has been found that some people with NSCLC have a change (mutation) in a certain gene called the EGFR gene. This mutated gene helps cancer cells grow. The majority of NSCLC patients with EGFR mutations achieve good outcomes with erlotinib or other EGFR inhibitor therapies, with a high response rate, prolonged progression-free survival and possibly improved overall survival from therapy. However, the 4% of EGFR mutant patients that harbor an exon 20 insertion mutation historically have reaped little benefit from EGFR-directed therapy due to the low affinity of this mutation for direct EGFR inhibitors, especially erlotinib and gefitinib (see Yasuda et al, Lancet Oncol 2011). This group of patients is ideal for studying other targeted therapeutic strategies that could affect the oncogene mutation in EGFR via alternative mechanisms.
AUY922 is an investigational drug that may stop cancer cells from growing abnormally. This drug has been used in other research studies. Information from those other research studies suggests that AUY922 may be effective in killing cancer cells in patients with exon 20 insertion mutations in EGFR.
The purpose of this study is to test the safety of AUY922 and determine how well AUY922 works for participants with advanced NSCLC and exon 20 insertion mutations in EGFR.
Detailed description
Interested patients will be asked to undergo some screening tests and procedures to confirm that they are eligible. Many of these tests and procedures are likely to be part of regular cancer care and may be done even if it turns out that patients do not take part in the research study. If patients have had some of these tests or procedures recently, they may or may not have to be repeated. These tests and procedures include: a medical history physical exam, performance status, assessment of tumor, EKG, electrocardiogram or multigated acquisition scan, eye exam, blood draw, blood pregnancy test, urine test and collection of a piece of the stored tumor tissue.
The study treatment is given in 21 day cycles. AUY922 is given by IV (into a vein). This is called an infusion. Patients will receive an infusion of AUY922 on days 1, 8 and 15 of each cycle (once per week). The infusion will take about 60 minutes.
A schedule of clinic visits for the study is summarized below.
Cycle 1, Day 1: physical exam, including measurement of vital signs and weight; performance status; EKG; blood draw; routine urine test Cycle 1, Day 2: EKG Cycle 1, Day 3: EKG Cycle 1, Day 8: Vital signs, performance status, EKG, questions about side effects and other medications taken Cycle 1, Day 15: Physical exam, including measurement of vital signs, performance status; EKG; blood draw; questions about side effects and other medications taken Note that in Cycle 1 patients will need to stay at (or return to) the clinic for the last EKG following the Day 1 AUY922 infusion, and come to the clinic on Days 2 and 3 for EKGs.
Cycle 2 and beyond, Day 1: physical exam, including measurement of vital signs and weight; performance status; EKG; blood draw; questions about side effects and other medications taken; routine urine test Cycle 2 and beyond, Day 8: Vital signs; performance status; EKG; questions about side effects and other medications taken Cycle 2 and beyond, Day 15: Physical exam, including measurement of vital signs; performance status; EKG; blood draw; questions about side effects and other medications taken.
Additional EKGs may be done at any time if the study doctor thinks it is necessary. A blood test to measure the amount of cardiac enzymes in the blood may be done whenever abnormal findings are suspected or seen on the EKG.
Additional tests and procedures:
- CT or MRI scans will be done to measure the disease about every 6 weeks.
- A blood pregnancy test, for women who can become pregnant, will be performed every 6 weeks or at any point in which pregnancy is suspected.
- A standard eye exam will be done on Cycle 3, Day 1. Additional eye exams will be done if patients experience any eye-related symptoms, such as changes in vision.
Within 1 week after the last dose of the study drug AUY922, patients will be asked to return to the clinic. At this visit the following will be done: physical examination, performance status, EKG, ECHO or MUGA scan, blood draw, urine test, eye exam, questions about side effects and other medications taken. Patients will be asked to return to the clinic a second time so investigators can follow-up on any ongoing side effects after stopping AUY922.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AUY922 Treatment Arm | Experimental | Drug: AUY922AUY922 administered once weekly via intravenous, 70 mg/m2 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Histologically or cytologically confirmed stage IV or recurrent NSCLC
- Measurable disease by RECIST 1.0
- Must have received at least one prior line of therapy for advanced lung cancer (no maximum number)
- Life expectancy of at least 12 weeks
Key exclusion criteria (21 listed)
- Pregnant or breastfeeding
- Radiation within 2 weeks
- Cytotoxic chemotherapy or monoclonal antibodies within 4 weeks
- EGFR tyrosine kinase inhibitor within 2 weeks
- Other small molecule inhibitor within 2 weeks
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AUY922AUY922 administered intravenously once a week at 70mg/m2 | Drug | AUY922 Treatment Arm |
Primary outcome
Overall Response Rate
Time frame: From the start of treatment until the time of disease progression, median duration of follow-up of about 3 months
The number of participants that achieved a response to treatment as assessed by Response Evaluation Criteria is Solid Tumors (RECIST). Response is defined as having achieved either a complete response (CR) or a partial response (PR). * Complete Response (CR): Disappearance of all target lesions. Any pathological lymph node must have reduction in short axis to < 10 mm. * Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
3 secondary outcomes
Median Progression Free and Overall Survival
Time frame: From the start of treatment until the time or death or disease progression
The Number of Participants With Treatment Related Serious Adverse Events
Time frame: From the start of treatment until 28 days after the end of treatment
Exon 20 EGFR Mutations Among Participants That Responded to Treatment
Time frame: Baseline, at the time of response
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Apr 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30351341Piotrowska Z, Costa DB, Oxnard GR, Huberman M, Gainor JF, Lennes IT, Muzikansky A, Shaw AT, Azzoli CG, Heist RS, Sequist LV. Activity of the Hsp90 inhibitor luminespib among non-small-cell lung cancers harboring EGFR exon 20 insertions. Ann Oncol. 2018 Oct 1;29(10):2092-2097. doi: 10.1093/annonc/mdy336.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lecia Sequist, MD, MPH principal investigator
Massachusetts General Hospital
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AUY922 in people with Non Small Cell Lung Cancer, run by Massachusetts General Hospital at 4 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 4 inclusion and 21 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 10 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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 phase mean?
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 10 Apr 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?
Overall Response Rate (time frame: From the start of treatment until the time of disease progression, median duration of follow-up of about 3 months). 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 NCT01854034, 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 10 Apr 2018.