Non Small Cell Lung CancerPhase 2NCT01752400
AUY922 for Advanced ALK-positive NSCLC
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. 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
- 6 participants
- Where
- 4 sitesUnited States
- Study dates
- Jan 2013to Nov 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 advanced NSCLC
- Tumor characterized by abnormalities in ALK
- Required to provide archival tissue in the form of 5 formalin fixed paraffin embedded sections
- Have acquired resistance to treatment with an ALK-TKI
- At least one measurable lesion as defined by RECIST criteria
- Life expectancy of at least 12 weeks
Who cannot join
- Pregnant or breastfeeding
- Discontinued ALK TKI more than four weeks prior to enrollment
- Unresolved diarrhea greater than or equal to CTCAE grade 1
- Not willing to use double barrier methods of contraception
- Prior anti-neoplastic treatment with any HSP90 or HDAC inhibitor compound
- Have received cytoxic chemotherapy in the intervening period since discontinuation of an ALK-TKI
Show all 15Show fewer
- Have undergone major surgery within 2 weeks prior to starting study drug
- Any concurrent or uncontrolled illness
- Any known disorders due to a deficiency in bilirubin glucuronidation
- Taking therapeutic doses of warfarin
- Any serious cardiac disorders or abnormalities
- Concurrent malignancies or invasive cancers diagnosed within the past 2 years except for adequately treated basal cell cancer of the skin or in situ cancers
- Known to be HIV positive
- Known hypersensitivity to any of the study drugs or their excipients
- Participation in another clinical study within 30 days before the first study treatment
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Beth Isreal 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: A Phase II Open-Label Trial of AUY922, an HSP90 Inhibitor, in Patients With ALK-Rearranged Advanced Non-Small Cell Lung Cancer and Acquired Resistance to Prior ALK Tyrosine Kinase Inhibition
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 and that research doctors are trying to find out more about it-such as the safest dose to use, the side effects it may cause and if the drug is effective for treating your type of cancer. 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 ALK gene. This mutated gene helps cancer cells grow. There is a drug (crizotinib) that has been approved by the FDA for the treatment of people with NSCLC who have mutations in the ALK gene. Most people respond to crizotinib initially. Over time, however, patients may stop responding (become resistant) to crizotinib because of additional changes in the ALK gene that makes crizotinib ineffective.
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 that have become resistant to drugs like crizotinib. Only participants with changes in the ALK gene will be allowed to participate in this study.
The purpose of this study is to test the safety of AUY922 and determine how well AUY922 treats participants with advanced, ALK-positive NSCLC.
Read the detailed description
If you agree to participate in this research study, you will be asked to undergo some screening tests or procedures to find out if you can be in the research study. 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 you do not take part in the research study. If you have had some of these tests or procedures recently, they may or may not have to be repeated. These test include a medical history, physical exam, performance status, assessment of tumor, EKG, echocardiogram or multigated acquisition scan, eye exam, blood draw, blood pregnancy test, urine tset and collection of a piece of stored tumor tissue. If these tests show you are eligible to participate in the research study, you will begin the study treatment. If you do not meet the eligibility criteria, you will not be able to participate in this research study.
Study treatment is given in 21 day cycles. AUY922 is given by IV (into a vein). This is called an infusion. You will receive an infusion of AUY922 jon 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. At every visit, you should tell the study staff how you are feeling and whether your health has changed. you may have other lab tests done as part of the the care of your cancer in addition to those listed below.
Cycle 1, Day 1: physical examination, performance status, EKG, Blood draw and routine urine tests.
Cycle 1, Day 2: EKG
Cycle 1, Day 3: EKG
Cycle 1, Day 8: measurement of weight and vital signs, performance status, EKG, questions about side effects you may have and medications you are taking
Cycle 1, Day 15: physical exam, performance status, EKG, blood draw, questions about side effects you may have and medications you are taking.
Note that in Cycle 1 you 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, performance status, EKG, blood draw, questions about side effects you may have and medications you are taking, routine urine test
Cycle 2 and beyond, Day 8: measurement of weight and vital signs, performance status, EKG, questions about side effects and medications
Cycle 2 and beyond, Day 15: physical exam, vital signs, performance status, EKG, blood draw, questions about side effects and medications
Additional EKGs may be done at any time if your study doctor thinks it is necessary. A blood test to measure the amount of cardiac enzymes in your blood may be done whenever abnormal findings such as heart rhythm changes are suspected or seen on the EKG. CT or MRI scans will be done to measure your 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 you experience any eye-related symptoms, such as changes in vision.
Within 1 week after your last dose of the study drug AUY922, you will be asked to return to the clinic for an End of Treatment Visit. At this visit the following will be done: physical examination, performance status, ECG, ECHO or MUGA scan, blood draw, urine test, eye exam, questions about side effects you may have and medications you are taking.
You will be asked to return to the clinic about 3 weeks after the End of Treatment Visit (about 4 weeks after the last dose of AUY922) so we can follow-up on any side effects you may still be experiencing after stopping AUY922.
If you decide to stop study treatment for a reason other than progression of your disease, you will be asked to have follow-up CT scans or MRIs every 12 weeks to continue to monitor the status of your cancer. If your tumors get worse, you will not need to have any further CT scans (or MRIs) as part of the study.
If your disease does progress, we would like to contact you by telephone about every 3 months to check on your status. This will be done until after the last participant stops study treatment, or for as long as you allow us to contact you. Keeping in touch with you and checking on your condition helps us look at the long term effects of the research.
You can continue to receive AUY922 for as long as your cancer does not progress and you do not experience unacceptable side effects.
- Conditions
- Non Small Cell Lung Cancer
- Being tested
- AUY922
- Keywords
- Advanced
- 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
| Study group | Role | What they receive |
|---|---|---|
| AUY922 | Experimental | Via intravenous infusion on Days 1, 8 and 15 of each 21 day cycle (once per week). Infusion lasts approximately 60 minutes Receives: Drug: AUY922 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate
The number of participants that achieved either a complete response (CR) or a partial response (PR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
- 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 and then every six weeks (± 7 days), until the time of disease progression
Secondary outcomes (7)
Progression-free Survival
Progression free survival is measured as the number of months from date of study entry to date of progression or death, whichever comes first. Progression is assessed using RECIST v1.1.
Progressive Disease (PD): 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 of death or progression
Disease Control Rate
The number of participants that achieved disease control, which includes complete responses, partial responses or stable disease as assessed by RECIST v1.1
- 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.
- Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Measured: Baseline and then every six weeks (± 7 days), until the time of disease progression
Number of Participants Who Develop Adverse Events on AUY922
The number of participants that developed any grade adverse event as assessed by Common Terminology Criteria for Adverse Events (CTCAE v4)
Measured: From the start of treatment until 30 days after last dose was received
Number of Participants With Concurrent KRAS Mutations
Measured: Baseline
ALK Translocation Variant Type
Measured: Baseline
ALK Mutation Status
The number of secondary ALK mutations or ALK amplification as a mechanism of resistance in pre-treatment and post-treatment biopsies.
Measured: Baseline, end of treatment
Median Overall Survival
The median duration of time from the start of treatment until the time of death or until the participant withdraws participation in the trial.
Measured: From the start of treatment until death or withdrawal from the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2012 (estimated)
- Study startJan 2013
- Primary completionJun 2017
- Study completionNov 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.
- 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
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Alice Shaw, Massachusetts General Hospital
- Investigators
- Alice Shaw, MD, PhD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01752400
- Sponsor's protocol ID
- 12-458
- Status last verified
- Mar 2018
- First submitted
- 7 Dec 2012
- Last updated
- 29 Mar 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Open-Label Trial of AUY922, an HSP90 Inhibitor, in Patients With ALK-Rearranged Advanced Non-Small Cell Lung Cancer and Acquired Resistance to Prior ALK Tyrosine Kinase Inhibition
- ClinicalTrials.gov ID
- NCT01752400
- Acronym / sponsor ID
- 12-458
- Conditions
- Non Small Cell Lung Cancer
- Keywords
- Advanced
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- Jan 2013
- Primary completion
- Jun 2017 (actual)
- Study completion
- Nov 2017 (actual)
- First posted
- 19 Dec 2012 (estimated)
- Results
- Posted 29 Mar 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 and that research doctors are trying to find out more about it-such as the safest dose to use, the side effects it may cause and if the drug is effective for treating your type of cancer. 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 ALK gene. This mutated gene helps cancer cells grow. There is a drug (crizotinib) that has been approved by the FDA for the treatment of people with NSCLC who have mutations in the ALK gene. Most people respond to crizotinib initially. Over time, however, patients may stop responding (become resistant) to crizotinib because of additional changes in the ALK gene that makes crizotinib ineffective.
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 that have become resistant to drugs like crizotinib. Only participants with changes in the ALK gene will be allowed to participate in this study.
The purpose of this study is to test the safety of AUY922 and determine how well AUY922 treats participants with advanced, ALK-positive NSCLC.
Detailed description
If you agree to participate in this research study, you will be asked to undergo some screening tests or procedures to find out if you can be in the research study. 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 you do not take part in the research study. If you have had some of these tests or procedures recently, they may or may not have to be repeated. These test include a medical history, physical exam, performance status, assessment of tumor, EKG, echocardiogram or multigated acquisition scan, eye exam, blood draw, blood pregnancy test, urine tset and collection of a piece of stored tumor tissue. If these tests show you are eligible to participate in the research study, you will begin the study treatment. If you do not meet the eligibility criteria, you will not be able to participate in this research study.
Study treatment is given in 21 day cycles. AUY922 is given by IV (into a vein). This is called an infusion. You will receive an infusion of AUY922 jon 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. At every visit, you should tell the study staff how you are feeling and whether your health has changed. you may have other lab tests done as part of the the care of your cancer in addition to those listed below.
Cycle 1, Day 1: physical examination, performance status, EKG, Blood draw and routine urine tests.
Cycle 1, Day 2: EKG
Cycle 1, Day 3: EKG
Cycle 1, Day 8: measurement of weight and vital signs, performance status, EKG, questions about side effects you may have and medications you are taking
Cycle 1, Day 15: physical exam, performance status, EKG, blood draw, questions about side effects you may have and medications you are taking.
Note that in Cycle 1 you 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, performance status, EKG, blood draw, questions about side effects you may have and medications you are taking, routine urine test
Cycle 2 and beyond, Day 8: measurement of weight and vital signs, performance status, EKG, questions about side effects and medications
Cycle 2 and beyond, Day 15: physical exam, vital signs, performance status, EKG, blood draw, questions about side effects and medications
Additional EKGs may be done at any time if your study doctor thinks it is necessary. A blood test to measure the amount of cardiac enzymes in your blood may be done whenever abnormal findings such as heart rhythm changes are suspected or seen on the EKG. CT or MRI scans will be done to measure your 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 you experience any eye-related symptoms, such as changes in vision.
Within 1 week after your last dose of the study drug AUY922, you will be asked to return to the clinic for an End of Treatment Visit. At this visit the following will be done: physical examination, performance status, ECG, ECHO or MUGA scan, blood draw, urine test, eye exam, questions about side effects you may have and medications you are taking.
You will be asked to return to the clinic about 3 weeks after the End of Treatment Visit (about 4 weeks after the last dose of AUY922) so we can follow-up on any side effects you may still be experiencing after stopping AUY922.
If you decide to stop study treatment for a reason other than progression of your disease, you will be asked to have follow-up CT scans or MRIs every 12 weeks to continue to monitor the status of your cancer. If your tumors get worse, you will not need to have any further CT scans (or MRIs) as part of the study.
If your disease does progress, we would like to contact you by telephone about every 3 months to check on your status. This will be done until after the last participant stops study treatment, or for as long as you allow us to contact you. Keeping in touch with you and checking on your condition helps us look at the long term effects of the research.
You can continue to receive AUY922 for as long as your cancer does not progress and you do not experience unacceptable side effects.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AUY922 | Experimental | Drug: AUY922Via intravenous infusion on Days 1, 8 and 15 of each 21 day cycle (once per week). Infusion lasts approximately 60 minutes |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Histologically or cytologically confirmed advanced NSCLC
- Tumor characterized by abnormalities in ALK
- Required to provide archival tissue in the form of 5 formalin fixed paraffin embedded sections
- Have acquired resistance to treatment with an ALK-TKI
- At least one measurable lesion as defined by RECIST criteria
Key exclusion criteria (15 listed)
- Pregnant or breastfeeding
- Discontinued ALK TKI more than four weeks prior to enrollment
- Unresolved diarrhea greater than or equal to CTCAE grade 1
- Not willing to use double barrier methods of contraception
- Prior anti-neoplastic treatment with any HSP90 or HDAC inhibitor compound
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 |
|---|---|---|
| AUY922 | Drug | AUY922 |
Primary outcome
Objective Response Rate
Time frame: Baseline and then every six weeks (± 7 days), until the time of disease progression
The number of participants that achieved either a complete response (CR) or a partial response (PR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST v1.1). * 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.
7 secondary outcomes
Progression-free Survival
Time frame: From the start of treatment until the time of death or progression
Disease Control Rate
Time frame: Baseline and then every six weeks (± 7 days), until the time of disease progression
Number of Participants Who Develop Adverse Events on AUY922
Time frame: From the start of treatment until 30 days after last dose was received
Number of Participants With Concurrent KRAS Mutations
Time frame: Baseline
ALK Translocation Variant Type
Time frame: Baseline
ALK Mutation Status
Time frame: Baseline, end of treatment
Median Overall Survival
Time frame: From the start of treatment until death or withdrawal from the study
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Alice Shaw, MD, PhD 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 6 inclusion and 15 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 29 Mar 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 29 Mar 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?
Objective Response Rate (time frame: Baseline and then every six weeks (± 7 days), until the time of disease progression). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 Mar 2018.