Unspecified Adult Solid Tumor, Protocol SpecificPhase 1NCT01602627
Hsp90 Inhibitor AUY922 in Treating Older Patients With Advanced Solid Malignancies
A Phase 1 study testing Hsp90 inhibitor AUY922, pharmacological study and laboratory biomarker analysis in people with Unspecified Adult Solid Tumor, Protocol Specific, run by Dale Shepard, MD, PhD at 1 site in United States.
Trial summary
This phase I trial studies the side effects and best dose of Hsp90 inhibitor AUY922 in treating older patients with advanced solid malignancies. Hsp90 inhibitor AUY922 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth Read more about this study
- Who is it for?
- Ages 75 years and older
- Conditions the study is for
- Unspecified Adult Solid Tumor, Protocol Specific
- What is being tested?
- Hsp90 inhibitor AUY922, pharmacological study and laboratory biomarker analysis
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2011to Feb 2012
- 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 75 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Patients must have a histologically proven solid tumor malignancy which is refractory to standard therapy and for which no curative therapy is available
- Patients must have at least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST); irradiated lesions are only evaluable for disease progression
- Eastern Cooperative Oncology Group (ECOG) Performance Status of =< 1
- Life expectancy of >= 12 weeks
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
- Hemoglobin (Hgb) >= 9 g/dl
Show all 18Show fewer
- Platelets (plt) >= 100 x 10^9/L
- Potassium within normal limits or correctable with supplements
- Total calcium (corrected for serum albumin) and phosphorus within normal limits
- Magnesium above lower limit of normal (LLN) or correctable with supplements
- Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) =< 2.5 x upper limit of normal (ULN) if no liver metastases are present
- AST/SGOT and ALT/SGPT =< 5 x 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
- Patients must be able to understand and voluntarily sign written informed consent
- Male participants with partners who are of child bearing potential must:
- Agree to use double barrier method of birth control 28 days prior to study entry, during course of study and for 28 days following the last dose of AUY922
- OR have history of a vasectomy
Who cannot join
- Patients with central nervous system (CNS) metastasis which are:
- Symptomatic or
- Require treatment for symptom control and/or
- Growing Note: Patients without clinical signs or symptoms of CNS involvement are not required to have a computed tomography (CT)/magnetic resonance imaging (MRI) of the brain
- Prior treatment with any heat shock protein (HSP)90 or histone deacetylase (HDAC) inhibitor compounds
- Patients who received systemic anti-cancer treatment prior to the first dose of AUY922 within the following time frames:
Show all 30Show fewer
- Radiotherapy or conventional chemotherapy: within 4 weeks
- Palliative radiotherapy: within 2 weeks
- Nitrosoureas, mitomycin, or monoclonal antibodies, such as trastuzumab, within 6 weeks
- Any systemic anti-cancer treatment for which the elimination period is not known, or investigational drugs (i.e. targeted agents) within a duration of =< 5 half lives of the agent and their active metabolites (if any)
- Treatment with therapeutic doses of coumadin-type anticoagulants (maximum daily dose of 2 mg, for line patency permitted)
- Unresolved diarrhea >= Common Terminology Criteria for Adverse Events (CTCAE) grade 1, despite treatment with antidiarrheal agents
- Patients with malignant ascites that require invasive treatment
- Male patients whose partners are women of child-bearing potential (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 Cycle 1, Day 1 or who have not recovered from such therapy; (placement of a venous access device within 2 weeks is permitted)
- Impaired cardiac function, including any one of the following:
- History (or family history) of long QT syndrome
- Mean corrected QT interval (QTc) >= 450 msec on baseline electrocardiogram (ECG)
- History of clinically manifested ischemic heart disease =< 6 months prior to study start
- History of heart failure or left ventricular (LV) dysfunction (left ventricular ejection fraction [LVEF] =< 45%) by multigated acquisition scan (MUGA) or echocardiogram (ECHO)
- Clinically significant ECG abnormalities including 1 or more of the following: left bundle branch block (LBBB), right bundle branch block (RBBB) with left anterior hemiblock (LAHB); ST segment elevation or depression > 1mm, or 2nd (Mobitz II), or 3rd degree atrioventricular (AV) block
- History or 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 an antihypertensive regimen)
- Clinically significant resting bradycardia (< 50 beats per minute)
- Patients who are currently receiving treatment with any medication which has a relative risk of prolonging the corrected QT using Bazett's formula (QTcB) interval or inducing Torsades de Pointes and cannot be switched or discontinued to an alternative drug prior to commencing AUY922
- Patients who are dependent on a pacemaker due to cardiac conduction dysfunction; known diagnosis of human immunodeficiency virus (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 unwilling or unable to comply with the protocol
Trial locations and contacts
1 site in 1 country.
United States1 site
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, 44195
About this study
Official title: A Phase I Dose Escalation, Single Center, Open-Label Study of AUY922 Administered IV on a Once-Weekly Schedule in Adult Patients 75 Years of Age or Older With Advanced Solid Malignancies
This phase I trial studies the side effects and best dose of Hsp90 inhibitor AUY922 in treating older patients with advanced solid malignancies. Hsp90 inhibitor AUY922 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth
Read the detailed description
PRIMARY OBJECTIVES:
- The primary objective is to determine the maximally tolerated dose (MTD) of AUY922 (Hsp90 inhibitor AUY922) as a single agent when administered intravenously (IV) on a once-weekly schedule to adult patients 75 years of age or older with advanced solid tumors whose disease has progressed despite standard therapy or for whom no standard therapy exists.
SECONDARY OBJECTIVES:
- To characterize the safety and tolerability of treatment with AUY922. II. To characterize the pharmacokinetic profiles of AUY922, including the parent drug and any potential metabolites.
III. To determine the efficacy of AUY922 in elderly patients with measurable disease.
IV. To evaluate of effect of geriatric-focused assessment of comorbidity and functional status on the toxicity and response to AUY922.
- To assess the ethical constraints to enrollment of elderly patients in phase I trials.
TERTIARY OBJECTIVES:
- Determine the effect of therapy with AUY922 on the number of circulating tumor cells (CTC).
II. To assess changes HSP70 induction as a measure of pharmacodynamic effect in pre- and post-AUY922 samples in peripheral blood mononuclear cell (PBMCs) to explore age-related differences in HSP90 inhibition by AUY922 compared with the previous phase I trial.
III. To assess changes in cellular response markers of apoptosis in pre- and post-AUY922 dosing in peripheral blood including measurement of M30 and M65 to explore age-related differences in pharmacodynamics compared to patients enrolled in the previous phase I trial.
IV. To determine associations between pharmacokinetic (PK) and pharmacodynamic (PD) parameters.
- To determine the relationship between geriatric-focused assessment of comorbidity and functional ability and toxicity and response.
OUTLINE: This is a dose-escalation study.
Patients receive Hsp90 inhibitor AUY922 IV over 1 hour on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 28 days.
- Being tested
- Hsp90 inhibitor AUY922, pharmacological study, laboratory biomarker analysis
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
Also called pharmacological studies
Correlative studies
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (enzyme inhibitor therapy) | Experimental | Patients receive Hsp90 inhibitor AUY922 IV over 1 hour on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: Hsp90 inhibitor AUY922; Other: pharmacological study; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
MTD of Hsp90 inhibitor AUY922
A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed as clinically relevant, and occurs < 28 days following the first dose of AUY922. Toxicity will be measured by CTCAE criteria (Version 4.02). The MTD will be determined using a standard design.
Measured: at 28 days
Secondary outcomes (8)
Toxicity by CTCAE (v 4.02)
Measured: at 28 days
Pharmacokinetic parameters, including area under the curve (AUC), clearance, volume of distribution (VD), time to the maximum concentration (Tmax), maximum plasma concentration (Cmax), and elimination half-life
Prior to 1st infusion; 30 minutes after start infusion; end infusion; 5, 30 minutes post-infusion; 1, 2, 4, 5, 24, 48 hours post-infusion course 1 days 8 (pretreatment) and 15 (pretreatment/end infusion); and course 2 day 1 (pretreatment/end infusion)
Measured: at baseline and at 28 days (first cycle)
Tumor response will be measured by RECIST criteria (complete response [CR], partial response [PR], stable disease [SD], progressive disease [PD], overall response [OR], response rate [RR])
Imaging with CT or MRI will be obtained at baseline (within 21 days of study Day 1) and every other cycle commencing at the end of cycle 2 (beginning of cycle 3). These scans should be schedule within 7 days of the start of the cycle. Imaging will be obtained at the end of the study.
Measured: at baseline and at end of cycle 2 (8 weeks)
Geriatric assessment will be made including Mini Mental Exam, Get up and Go, assessment of comorbidity, and Geriatric Depression Scale
This trial will incorporate geriatric assessment to determine the relationship between functional ability or comorbidity and treatment response or toxicity. Patients will be have a geriatric assessment which will included a range of assessments, such as mini mental status, up and go test, and the geriatric depression scale, at baseline and after every 2 cycles of therapy.
Measured: at baseline and at end of cycle 2 (8 weeks)
Evaluation of responses to a bioethics questionnaire will be used to assess patient factors influencing enrollment in this elderly-specific phase I trial
Measured: Baseline
Number of Circulating Tumor Cells (CTC) at baseline and after treatment with Hsp90 inhibitor AUY922
Blood will be collected for measurement of CTCs on Cycle 1 Day 1 pre-infusion, Cycle 2 Day 1 pre-infusion, Cycle 3 Day 1, pre-infusion, then Day 1 of every other cycle until the end of the study.
Measured: at baseline and end of treatment
Level of HSP70 at baseline and after treatment with Hsp90 inhibitor AUY922
Measured: at baseline and at 28 days (first cycle)
Level of M30 and M65 at baseline and following therapy with Hsp90 inhibitor AUY922
Measured: at baseline and at 28 days (first cycle)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2012 (estimated)
- Study startSep 2011
- Primary completionFeb 2012
- Study completionFeb 2012
Why it stopped: Slow accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Unspecified Adult Solid Tumor, Protocol SpecificStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dale Shepard, MD, PhD
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor-investigator, Dale Shepard, MD, PhD, Case Comprehensive Cancer Center
- Investigators
- Dale Shepard, Principal investigator, Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01602627
- Sponsor's protocol ID
- CASE3Y10
- Other IDs
- NCI-2011-03107
- Status last verified
- Feb 2013
- First submitted
- 16 May 2012
- Last updated
- 7 Feb 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Dose Escalation, Single Center, Open-Label Study of AUY922 Administered IV on a Once-Weekly Schedule in Adult Patients 75 Years of Age or Older With Advanced Solid Malignancies
- ClinicalTrials.gov ID
- NCT01602627
- Acronym / sponsor ID
- CASE3Y10
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow accrual
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Dale Shepard, MD, PhDUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Sep 2011
- Primary completion
- Feb 2012 (actual)
- Study completion
- Feb 2012 (actual)
- First posted
- 21 May 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase I trial studies the side effects and best dose of Hsp90 inhibitor AUY922 in treating older patients with advanced solid malignancies. Hsp90 inhibitor AUY922 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth
Detailed description
PRIMARY OBJECTIVES:
- The primary objective is to determine the maximally tolerated dose (MTD) of AUY922 (Hsp90 inhibitor AUY922) as a single agent when administered intravenously (IV) on a once-weekly schedule to adult patients 75 years of age or older with advanced solid tumors whose disease has progressed despite standard therapy or for whom no standard therapy exists.
SECONDARY OBJECTIVES:
- To characterize the safety and tolerability of treatment with AUY922. II. To characterize the pharmacokinetic profiles of AUY922, including the parent drug and any potential metabolites.
III. To determine the efficacy of AUY922 in elderly patients with measurable disease.
IV. To evaluate of effect of geriatric-focused assessment of comorbidity and functional status on the toxicity and response to AUY922.
- To assess the ethical constraints to enrollment of elderly patients in phase I trials.
TERTIARY OBJECTIVES:
- Determine the effect of therapy with AUY922 on the number of circulating tumor cells (CTC).
II. To assess changes HSP70 induction as a measure of pharmacodynamic effect in pre- and post-AUY922 samples in peripheral blood mononuclear cell (PBMCs) to explore age-related differences in HSP90 inhibition by AUY922 compared with the previous phase I trial.
III. To assess changes in cellular response markers of apoptosis in pre- and post-AUY922 dosing in peripheral blood including measurement of M30 and M65 to explore age-related differences in pharmacodynamics compared to patients enrolled in the previous phase I trial.
IV. To determine associations between pharmacokinetic (PK) and pharmacodynamic (PD) parameters.
- To determine the relationship between geriatric-focused assessment of comorbidity and functional ability and toxicity and response.
OUTLINE: This is a dose-escalation study.
Patients receive Hsp90 inhibitor AUY922 IV over 1 hour on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 28 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (enzyme inhibitor therapy) | Experimental | Drug: Hsp90 inhibitor AUY922, Other: pharmacological study, Other: laboratory biomarker analysisPatients receive Hsp90 inhibitor AUY922 IV over 1 hour on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 75 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (18 listed)
- Patients must have a histologically proven solid tumor malignancy which is refractory to standard therapy and for which no curative therapy is available
- Patients must have at least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST); irradiated lesions are only evaluable for disease progression
- Eastern Cooperative Oncology Group (ECOG) Performance Status of =< 1
- Life expectancy of >= 12 weeks
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
Key exclusion criteria (30 listed)
- Symptomatic or
- Require treatment for symptom control and/or
- Growing Note: Patients without clinical signs or symptoms of CNS involvement are not required to have a computed tomography (CT)/magnetic resonance imaging (MRI) of the brain
- Prior treatment with any heat shock protein (HSP)90 or histone deacetylase (HDAC) inhibitor compounds
- Patients who received systemic anti-cancer treatment prior to the first dose of AUY922 within the following time frames:
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 |
|---|---|---|
| Hsp90 inhibitor AUY922Also: AUY922Given IV | Drug | Treatment (enzyme inhibitor therapy) |
| pharmacological studyAlso: pharmacological studiesCorrelative studies | Other | Treatment (enzyme inhibitor therapy) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (enzyme inhibitor therapy) |
Primary outcome
MTD of Hsp90 inhibitor AUY922
Time frame: at 28 days
A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed as clinically relevant, and occurs < 28 days following the first dose of AUY922. Toxicity will be measured by CTCAE criteria (Version 4.02). The MTD will be determined using a standard design.
8 secondary outcomes
Toxicity by CTCAE (v 4.02)
Time frame: at 28 days
Pharmacokinetic parameters, including area under the curve (AUC), clearance, volume of distribution (VD), time to the maximum concentration (Tmax), maximum plasma concentration (Cmax), and elimination half-life
Time frame: at baseline and at 28 days (first cycle)
Tumor response will be measured by RECIST criteria (complete response [CR], partial response [PR], stable disease [SD], progressive disease [PD], overall response [OR], response rate [RR])
Time frame: at baseline and at end of cycle 2 (8 weeks)
Geriatric assessment will be made including Mini Mental Exam, Get up and Go, assessment of comorbidity, and Geriatric Depression Scale
Time frame: at baseline and at end of cycle 2 (8 weeks)
Evaluation of responses to a bioethics questionnaire will be used to assess patient factors influencing enrollment in this elderly-specific phase I trial
Time frame: Baseline
Number of Circulating Tumor Cells (CTC) at baseline and after treatment with Hsp90 inhibitor AUY922
Time frame: at baseline and end of treatment
Level of HSP70 at baseline and after treatment with Hsp90 inhibitor AUY922
Time frame: at baseline and at 28 days (first cycle)
Level of M30 and M65 at baseline and following therapy with Hsp90 inhibitor AUY922
Time frame: at baseline and at 28 days (first cycle)
Results and safety
The study was stopped early (reason given: Slow accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2013.
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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.
Dale Shepard principal investigator
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Hsp90 inhibitor AUY922, pharmacological study and laboratory biomarker analysis in people with Unspecified Adult Solid Tumor, Protocol Specific, run by Dale Shepard, MD, PhD 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 18 inclusion and 30 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: stopped early, as of the sponsor's last update on 7 Feb 2013. 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 was stopped early (reason given: Slow accrual). Results are not available in the source record.
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?
MTD of Hsp90 inhibitor AUY922 (time frame: at 28 days). 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 7 Feb 2013.