AZD5153 in Patients With Relapsed or Refractory Solid Tumors, Including Lymphomas

Completed · Phase 1

Conditions studied: Malignant Solid Tumors, Lymphoma, Ovarian Cancer, Breast Cancer, Pancreatic Cancer, Prostate Cancer

In brief

This is a first-time-in-man (FTIM) multicenter, dose escalation study designed to investigate the safety, pharmacokinetics, and pharmacodynamics of AZD5153 in patients with malignant solid tumors, including lymphomas.

Key facts

Study ID

NCT03205176

Run by

AstraZeneca

People needed

49

Starts

2017-06-30

Expected to finish

2021-04-08

Last updated by the study team

2021-05-06

Who can join

Age: 18 and older, up to 130. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

• Patients who have been treated with most recent chemotherapy, radiotherapy, hormonal therapy, immunotherapy or investigational drugs within 21 days or 5 half-lives (whichever is shorter) from enrollment.
• Minimum wash-out period for previous PARPi therapy is at least 14 days or 5 half-lives whichever is shorter, or until toxicity from previous PARPi therapy has fully recovered.
• Patient received more than 5 prior lines of treatment for an advanced solid tumor (including HGSO cancer, TNBC, mCRPC, or PDAC). Patients with lymphoma will be able to enroll without a restriction in the number of previous therapies received, if they otherwise meet eligibility criteria.
• Major surgery (excluding placement of vascular access) ≤ 21 days from the beginning of enrollment or minor surgical procedures ≤ 7 days. No waiting is required following implantable port and catheter placement.
• Patient is unable to swallow oral medications or has a gastrointestinal disorder (e.g., malabsorption) that would jeopardize intestinal absorption of AZD5153 and olaparib.
• Treatment with any of the following:
• Patient has had prescription or non-prescription drugs or other products known to be strong or moderate inhibitors/inducers of CYP3A4/5, or CYP3A4/5 sensitive substrates or substrates with a narrow therapeutic range, which cannot be discontinued 2 weeks prior to the first day of dosing and withheld throughout the study until 2 weeks after the last dose of AZD5153 and/or olaparib.
• Drugs that are sensitive substrates of the transporters P-gp, UGT1A1, BCRP, OATP1B1, OAT3, OCT1, OCT2, MATE1 and MATE2K.
• Herbal preparations/medications are not allowed throughout the study. These herbal medications include, but are not limited to: St. John's wort, kava, ephedra (ma huang), ginkgo biloba, dehydroepiandrosterone, yohimbe, saw palmetto, and ginseng. Patients should stop using these herbal medications 14 days prior to the first dose of AZD5153 and/or olaparib.
• Drugs known to prolong QT interval or induce Torsades de Pointes.
• Refractory nausea and vomiting, previous significant bowel resection that would preclude adequate absorption of study drug and chronic gastrointestinal disease including active or prior documented inflammatory bowel disease.
• Patient has a history of tuberculosis.
• Patients receiving a live attenuated vaccine ≤28 days before the first dose of study drug.
• Spinal cord compression or brain metastases unless asymptomatic, treated and stable and not requiring steroids for at least 4 weeks prior to start of study treatment.
• A diagnosis of MDS or secondary AML (for olaparib combination dose escalation only)
• As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses, or active infection including hepatitis B, hepatitis C, human immunodeficiency virus (HIV) or other comorbidity that renders the patient unsuitable for participation in the study. Screening for chronic conditions is not required.
• Any of the following cardiac criteria:
• Mean resting corrected QT interval (QTcF) >450 msec obtained from 3 electrocardiograms (ECGs).
• Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g., complete left bundle branch block, third degree heart block.
• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age.
• History of hypersensitivity to active or inactive excipients of AZD5153 and/or olaparib or drugs with a similar chemical structure or class to AZD5153 and/or olaparib.
• Patients with non-Hodgkin lymphoma (NHL) at high risk for developing tumor lysis syndrome are not eligible for the monotherapy dose escalation part of this study.
• Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.
• Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.

Where it is running

• Research Site — Sarasota, Florida, United States
• Research Site — Oklahoma City, Oklahoma, United States
• Research Site — Nashville, Tennessee, United States
• Research Site — Toronto, CA, Canada

Full record on ClinicalTrials.gov

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