Onalespib and CDKI AT7519 in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery

NCT ID: NCT02503709

Last Updated: 2025-02-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-30
• Study Completion Date: 2020-10-09

Brief 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. 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:

I. To establish the safety, tolerability, and the maximum tolerated dose of the combination of onalespib and AT7519M (CDKI AT7519).

SECONDARY OBJECTIVES:

I. 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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (onalespib, CDKI AT7519)

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.

Group Type: EXPERIMENTAL

CDK Inhibitor AT7519

Intervention Type: DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Onalespib

Intervention Type: DRUG

Given IV

Pharmacological Study

Intervention Type: OTHER

Correlative studies

Interventions

CDK Inhibitor AT7519

Given IV

Intervention Type: DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Onalespib

Given IV

Intervention Type: DRUG

Pharmacological Study

Correlative studies

Intervention Type: OTHER

Other Intervention Names

AT-7519; AT7519; AT7519M; CDK inhibitor AT7519M; Cyclin-Dependent Kinase Inhibitor AT7519M; AT 13387; AT-13387; AT13387

Eligibility Criteria

Inclusion Criteria

• 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
• 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

Exclusion Criteria

• 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
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Khanh T Do

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber - Harvard Cancer Center LAO

Locations

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, United States

National Cancer Institute Developmental Therapeutics Clinic

Bethesda, Maryland, United States

National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Countries

United States

Other Identifiers

NCI-2015-01098

Identifier Type: REGISTRY

Identifier Source: secondary_id

P9899

Identifier Type: -

Identifier Source: secondary_id

L9899

Identifier Type: -

Identifier Source: secondary_id

UK11143

Identifier Type: -

Identifier Source: secondary_id

16-711

Identifier Type: -

Identifier Source: secondary_id

9899

Identifier Type: OTHER

Identifier Source: secondary_id

9899

Identifier Type: OTHER

Identifier Source: secondary_id

UM1CA186709

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ZIABC011078

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2015-01098

Identifier Type: -

Identifier Source: org_study_id