Advanced Malignant Solid NeoplasmPhase 1NCT02503709
Onalespib and CDKI AT7519 in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery
A Phase 1 study testing CDK Inhibitor AT7519, Laboratory Biomarker Analysis and Onalespib in people with Advanced Malignant Solid Neoplasm and Metastatic Malignant Solid Neoplasm, run by National Cancer Institute (NCI) at 6 sites in United States.
Trial summary
This phase I trial studies the side effects and best dose of onalespib and CDKI AT7519 in treating patients with solid tumors that have spread from the primary site (place where they started) to other places in the body (metastatic) or cannot be removed by surgery. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Malignant Solid Neoplasm, Metastatic Malignant Solid Neoplasm, Unresectable Solid Neoplasm
- What is being tested?
- CDK Inhibitor AT7519, Laboratory Biomarker Analysis and Onalespib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 6 sitesUnited States
- Study dates
- 30 Sep 2016to 9 Oct 2020
- 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
- Patients must have histologically confirmed solid tumor that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
- Patients must have evaluable disease or disease measurable per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1; measurable disease is defined as at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm (>= 2 cm) with conventional techniques or as >= 10 mm (>= 1 cm) with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
- There are no limits on prior lines of therapy; however, patients must have recovered to eligibility levels from prior toxicity or adverse events as a result of previous treatment prior to entering the study (except alopecia)
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Life expectancy of greater than 3 months
- Absolute neutrophil count >= 1,500/microliters
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- Platelets >= 100,000/microliters
- Total bilirubin =< 1.5 X institutional upper limit of normal
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
- Creatinine < 1 X institutional upper limit of normal OR creatinine clearance >= 50 mL/min determined by Cockcroft-Gault formula
- Creatine phosphokinase =< institutional upper limit of normal
- The effects of onalespib and AT7519M on the developing human fetus are unknown; for this reason, women of childbearing potential and male patients with partners of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry, for the duration of study participation, and for 2 months after completion of study; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; women of childbearing potential enrolling on study must have a negative pregnancy test within 72 hours of enrollment in order to be eligible; because there is an unknown but potential risk to nursing infants secondary to treatment of the mother with onalespib and AT7519M, breastfeeding should be discontinued while the mother is treated with onalespib and AT7519M
- Ability to understand and the willingness to sign a written informed consent document
Who cannot join
- Patients who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study; patients who have had prior onalespib or AT7519M as a monotherapy will not be excluded
- Patients who are receiving any other investigational agents
- Patients with known brain metastases or carcinomatous meningitis are excluded from this clinical trial, with the exception of patients with brain metastatic disease that has previously been treated and remained stable on MRI >= 2 months after treatment, without steroids or anti-epileptic medications; these patients may be enrolled at the discretion of the principal investigator
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to onalespib or AT7519M
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements; additionally, patients with other co-morbid disease or metabolic dysfunction that would render the subject at high risk for treatment complications may be excluded at the discretion of the principal investigator in the interest of patient safety
- The effects of onalespib and AT7519M on the developing human fetus are unknown; for this reason, pregnant women are excluded from this study
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- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy known to interact with CYP isoenzymes are ineligible; in addition, HIV patients with CD4 count < 200 cells/uL are ineligible; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
- Consistent corrected QT (QTc) > 450 msec for men and > 470 msec for women by Fridericia formula, on 3 separate electrocardiograms (ECGs); patients with a history of long QTc syndrome or personal or family history of ventricular arrhythmias will be excluded
- Patients with pre-existing retinal disease on ophthalmologic exam will be excluded due to potential eye toxicities known to be associated with onalespib
- Patients with left ventricular ejection fraction < 50% on echocardiogram or multigated acquisition scan will be excluded based on known cardiotoxicities associated with onalespib
- Patients with grade >= 2 peripheral neuropathy will not be permitted on study
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
National Cancer Institute Developmental Therapeutics Clinic
Bethesda, Maryland, 20892
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007
About this study
Official title: A Phase 1 Trial of the Combination of the Heat Shock Protein-90 (HSP90) Inhibitor Onalespib (AT13387) and the Cyclin-Dependent Kinase (CDK) Inhibitor AT7519M in Patients With Advanced Solid Tumors
This phase I trial studies the side effects and best dose of onalespib and CDKI AT7519 in treating patients with solid tumors that have spread from the primary site (place where they started) to other places in the body (metastatic) or cannot be removed by surgery. Onalespib and CDKI AT7519 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Read the detailed description
PRIMARY OBJECTIVES:
- To establish the safety, tolerability, and the maximum tolerated dose of the combination of onalespib and AT7519M (CDKI AT7519).
SECONDARY OBJECTIVES:
- To determine the pharmacokinetics of the combination of onalespib and AT7519M.
II. To assess the pharmacodynamic effect of the combination of onalespib and AT7519M on HSP70 expression and modulation of HSP90 client proteins in peripheral blood mononuclear cells (PBMCs), plasma, and tumor biopsies.
III. To observe and record anti-tumor activity.
OUTLINE: This is a dose-escalation study.
Patients receive onalespib intravenously (IV) over 1 hour on days 1 and 4 (cycle 0 only). Patients then receive onalespib IV over 1 hour and CDKI AT7519 IV over 1 hour on days 1, 4, 8, and 11 (cycle 1 and subsequent cycles thereafter). Cycles repeat every 21 days (7 days for course 0 only) in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
- Conditions
- Advanced Malignant Solid Neoplasm, Metastatic Malignant Solid Neoplasm, Unresectable Solid Neoplasm
- Being tested
- CDK Inhibitor AT7519, Laboratory Biomarker Analysis, Onalespib, Pharmacological Study
- Medical subject headings
- Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CDK Inhibitor AT7519Drug
Also called AT-7519, AT7519, AT7519M, CDK inhibitor AT7519M
Given IV
Laboratory Biomarker AnalysisOther
Correlative studies
OnalespibDrug
Also called AT 13387, AT-13387, AT13387
Given IV
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (onalespib, CDKI AT7519) | Experimental | Patients receive onalespib IV over 1 hour on days 1 and 4 (cycle 0 only). Patients then receive onalespib IV over 1 hour and CDKI AT7519 IV over 1 hour on days 1, 4, 8, and 11 (cycle 1 and subsequent cycles thereafter). Cycles repeat every 21 days (7 days for course 0 only) in the absence of disease progression or unacceptable toxicity. Receives: Drug: CDK Inhibitor AT7519; Other: Laboratory Biomarker Analysis; Drug: Onalespib; Other: Pharmacological Study |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events of onalespib and CDKI AT7519
Scored using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Measured: Up to 30 days after the last dose of study drug
Tolerability of onalespib and CDKI AT7519
Assessed using the NCI CTCAE version 5.0.
Measured: Up to 30 days after the last dose of study drug
Maximum tolerated dose of onalespib and CDKI AT7519
Defined as =< 1 out of 6 patients experiencing dose limiting toxicity.
Measured: 21 days
Secondary outcomes (3)
Pharmacokinetic parameters of onalespib and CDKI AT7519
Individual patient plasma concentration-time curves will be analyzed by noncompartmental methods using routines supplied in the WinNonlin Professional Version 4.0.1 software package. Pharmacokinetic parameters and variables will be calculated according to standard equations. Mean values of the pharmacokinetic parameters will be statistically compared using the paired two-tailed t-test of the log-transformed data.
Measured: Before infusion, at 30 and 59 minutes of infusion, and at 1.5, 2, 4, 6, 8, and 24 hours at end of infusion on day 1 of course 0 and days 1 and 11 of course 1
Pharmacodynamic (PD) parameters of onalespib and CDKI AT7519
PD effect of the combination of onalespib and CDKI AT7519 on Hsp70 expression and modulation of Hsp90 client proteins in peripheral blood mononuclear cells (PBMCs) will be assessed. All PD evaluations and comparisons will be done with exploratory intent, using primarily descriptive and non-parametric techniques.
Measured: Prior to onalespib administration during course 0, 2-4 hours after completion of onalespib on day 4 of course 0, and 2-4 hours after completion of CDKI AT7519 on day 11 of course 1
Antitumor activity of the combination
Measured by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v.1.1).
Measured: Up to 30 days after the last dose of study drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2015 (estimated)
- Study start30 Sep 2016
- Primary completion15 Aug 2020
- Study completion9 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Malignant Solid NeoplasmStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Khanh T Do, Principal investigator, Dana-Farber - Harvard Cancer Center LAO
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02503709
- Sponsor's protocol ID
- NCI-2015-01098
- Other IDs
- NCI-2015-01098, P9899, L9899, UK11143, 16-711, 9899, 9899, UM1CA186709
- Status last verified
- Feb 2025
- First submitted
- 20 Jul 2015
- Last updated
- 10 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Trial of the Combination of the Heat Shock Protein-90 (HSP90) Inhibitor Onalespib (AT13387) and the Cyclin-Dependent Kinase (CDK) Inhibitor AT7519M in Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT02503709
- Acronym / sponsor ID
- NCI-2015-01098
- Conditions
- Advanced Malignant Solid Neoplasm, Metastatic Malignant Solid Neoplasm, Unresectable Solid Neoplasm
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 30 Sep 2016 (actual)
- Primary completion
- 15 Aug 2020 (actual)
- Study completion
- 9 Oct 2020 (actual)
- First posted
- 21 Jul 2015 (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 onalespib and CDKI AT7519 in treating patients with solid tumors that have spread from the primary site (place where they started) to other places in the body (metastatic) or cannot be removed by surgery. Onalespib and CDKI AT7519 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed description
PRIMARY OBJECTIVES:
- To establish the safety, tolerability, and the maximum tolerated dose of the combination of onalespib and AT7519M (CDKI AT7519).
SECONDARY OBJECTIVES:
- To determine the pharmacokinetics of the combination of onalespib and AT7519M.
II. To assess the pharmacodynamic effect of the combination of onalespib and AT7519M on HSP70 expression and modulation of HSP90 client proteins in peripheral blood mononuclear cells (PBMCs), plasma, and tumor biopsies.
III. To observe and record anti-tumor activity.
OUTLINE: This is a dose-escalation study.
Patients receive onalespib intravenously (IV) over 1 hour on days 1 and 4 (cycle 0 only). Patients then receive onalespib IV over 1 hour and CDKI AT7519 IV over 1 hour on days 1, 4, 8, and 11 (cycle 1 and subsequent cycles thereafter). Cycles repeat every 21 days (7 days for course 0 only) in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 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 (onalespib, CDKI AT7519) | Experimental | Drug: CDK Inhibitor AT7519, Other: Laboratory Biomarker Analysis, Drug: Onalespib, Other: Pharmacological StudyPatients receive onalespib IV over 1 hour on days 1 and 4 (cycle 0 only). Patients then receive onalespib IV over 1 hour and CDKI AT7519 IV over 1 hour on days 1, 4, 8, and 11 (cycle 1 and subsequent cycles thereafter). Cycles repeat every 21 days (7 days for course 0 only) in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Patients must have histologically confirmed solid tumor that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
- Patients must have evaluable disease or disease measurable per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1; measurable disease is defined as at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm (>= 2 cm) with conventional techniques or as >= 10 mm (>= 1 cm) with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
- There are no limits on prior lines of therapy; however, patients must have recovered to eligibility levels from prior toxicity or adverse events as a result of previous treatment prior to entering the study (except alopecia)
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Life expectancy of greater than 3 months
Key exclusion criteria (11 listed)
- Patients who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study; patients who have had prior onalespib or AT7519M as a monotherapy will not be excluded
- Patients who are receiving any other investigational agents
- Patients with known brain metastases or carcinomatous meningitis are excluded from this clinical trial, with the exception of patients with brain metastatic disease that has previously been treated and remained stable on MRI >= 2 months after treatment, without steroids or anti-epileptic medications; these patients may be enrolled at the discretion of the principal investigator
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to onalespib or AT7519M
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements; additionally, patients with other co-morbid disease or metabolic dysfunction that would render the subject at high risk for treatment complications may be excluded at the discretion of the principal investigator in the interest of patient safety
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 |
|---|---|---|
| CDK Inhibitor AT7519Also: AT-7519, AT7519, AT7519M, CDK inhibitor AT7519MGiven IV | Drug | Treatment (onalespib, CDKI AT7519) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (onalespib, CDKI AT7519) |
| OnalespibAlso: AT 13387, AT-13387, AT13387Given IV | Drug | Treatment (onalespib, CDKI AT7519) |
| Pharmacological StudyCorrelative studies | Other | Treatment (onalespib, CDKI AT7519) |
Primary outcome
Incidence of adverse events of onalespib and CDKI AT7519
Time frame: Up to 30 days after the last dose of study drug
Scored using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Tolerability of onalespib and CDKI AT7519
Time frame: Up to 30 days after the last dose of study drug
Assessed using the NCI CTCAE version 5.0.
Maximum tolerated dose of onalespib and CDKI AT7519
Time frame: 21 days
Defined as =< 1 out of 6 patients experiencing dose limiting toxicity.
3 secondary outcomes
Pharmacokinetic parameters of onalespib and CDKI AT7519
Time frame: Before infusion, at 30 and 59 minutes of infusion, and at 1.5, 2, 4, 6, 8, and 24 hours at end of infusion on day 1 of course 0 and days 1 and 11 of course 1
Pharmacodynamic (PD) parameters of onalespib and CDKI AT7519
Time frame: Prior to onalespib administration during course 0, 2-4 hours after completion of onalespib on day 4 of course 0, and 2-4 hours after completion of CDKI AT7519 on day 11 of course 1
Antitumor activity of the combination
Time frame: Up to 30 days after the last dose of study drug
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2025.
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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.
Khanh T Do principal investigator
Dana-Farber - Harvard Cancer Center LAO
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CDK Inhibitor AT7519, Laboratory Biomarker Analysis and Onalespib in people with Advanced Malignant Solid Neoplasm and Metastatic Malignant Solid Neoplasm, run by National Cancer Institute (NCI) at 6 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 13 inclusion and 11 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 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 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 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 of onalespib and CDKI AT7519 (time frame: Up to 30 days after the last dose of study drug). The study lists 3 primary outcomes in all. 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 10 Feb 2025.