Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Skin and Connective Tissue Diseases

Digestive System Diseases

Gland and Hormone Related Diseases

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Prostatic Neoplasms

Breast Neoplasms

Triple Negative Breast Neoplasms

Pancreatic Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Lymphoma

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Gonadal Disorders

Pancreatic Cancer

Ovarian Cancer

Ovarian Epithelial Cancer

Lymphosarcoma

Antineoplastic Agents

All Drugs and Chemicals

Olaparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Patients will be enrolled in cohorts of up to 6 patients each in a dose escalating scheme to determine maximum tolerated dose (MTD). AZD5153 will be taken once per day (QD) or two times per day (BID) for 21 days as an oral capsule. Once the MTD is finalized, patients may be enrolled into an expansion cohort at the MTD.

Patients will be enrolled in cohorts of up to 6 patients each in a dose escalating scheme to determine MTD. AZD5153 will be taken as oral capsules BID in combination with 300 mg olaparib BID for 21 days.

AZD5153 is to be taken as oral capsules once or twice per day each day in 21 day cycles. Dosing will continue until disease progression or other study discontinuation criteria are met.

AZD5153

Olaparib, 300 mg, will be taken BID as oral capsules.

Erika P Hamilton, MD

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.

The trial will be conducted in two parts, dose escalation and dose expansion. AZD5153 will be investigated as a monotherapy and in combination with olaparib.

AZD5153 monotherapy (dose escalation):

This part of the study will enroll patients with advanced solid malignancies, including lymphoma, and test safety and tolerability of AZD5153 administered as a monotherapy. The dose escalation will proceed by two-fold increments or through lower doses suggested by the CRM until an MTD as defined by dose-limiting toxicity is reached.

Single daily (QD) and twice daily (BID) dosing schedules will be explored in the monotherapy cohort. Additional dose levels or dosing schedules may be evaluated and recommended by study Safety Review Committee (SRC) based on the emerging PK and safety data.

When the AZD5153 monotherapy MTD is established, an expansion cohort consisting of up to 12 additional evaluable patients may be enrolled to confirm the safety and tolerability of the MTD. The dose expansion will be initiated and will enroll patients with histologically or cytologically confirmed platinum resistant or platinum-refractory high grade serous ovarian (HGSO) cancer.

Mandatory tumor biopsies at screening for ovarian cancer patients will be required for patient enrollment in the MTD dose expansion cohort. Optional on-treatment biopsies will be requested from consenting patients in the ovarian expansion cohort.

AZD5153 + olaparib combination:

Dose escalation of AZD5153 in combination with olaparib will also be investigated while the AZD5153 monotherapy dose escalation is ongoing and prior to determination of a monotherapy MTD.

The starting dose of AZD5153 in combination with olaparib will be a dose that has been shown to be safe and tolerated in monotherapy and has been chosen because clinical exposure achieved at this dose is equivalent to preclinical exposure causing tumour growth inhibition in animal models. If the starting dose in combination with olaparib is safe and tolerated, the dose of AZD5153 will be escalated, using the same method as for the monotherapy part of the study, keeping the olaparib dose fixed at 300 mg BID. Intermittent schedules as well as continuous BID or QD dosing of AZD5153 in combination with 300 mg BID olaparib might be tested until a safe and tolerated combination dose and schedule is determined. However, the total dose per cycle of AZD5153 used in combination with olaparib won't exceed the total dose per cycle that has been shown to be safe and tolerated as a monotherapy, and won't be higher than the dose declared to be the monotherapy MTD. If intermittent dosing is explored then the CRM will consider cumulative dosing rather than daily dosing.

AZD5153 and olaparib will be administered in continuous cycles of 21 days. The combination dose escalation part will run in parallel with the AZD5153 monotherapy part (dose escalation and expansion) and will continue until a safe and tolerated combination dose of the two agents is declared. Mandatory paired tumor biopsies at screening and on-treatment will be required for patients enrolled into the combination dose escalation.

Once a dose and schedule of AZD5153 in combination with olaparib is established, up to 12 additional evaluable patients might be enrolled to confirm the safety and tolerability of the dose and schedule of AZD5153 and olaparib in one or more of the indications where clinical activity is observed. Patients with platinum-resistant or platinum-refractory HGSO cancer, triple negative breast cancer, metastatic castration resistant prostate cancer, or pancreatic ductal adenocarcinoma will be eligible for the expansion cohort.

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

A Phase I, Multicenter Dose-Escalation Study to Assess the Tolerability, Pharmacokinetics and Preliminary Anti-tumor Activity of AZD5153 in Patients With Relapsed/Refractory Malignant Solid Tumors, Including Lymphomas

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

DLTs will be determined from monitoring adverse events (AEs), and abnormal laboratory tests (clinical chemistry, hematology, and urinalysis), physical examinations, vital signs (blood pressure and pulse), and electrocardiogram (ECG).

The concentration of AZD5153 and its co-former in blood and plasma will be determined (Cmax will be derived).

Total urine volume will be measured for each interval and urine concentration of AZD5153 will be determined. A sample for the determination of 1β-hydroxy deoxycholic acid will be taken from the total urine collection at each scheduled time interval.

Triplicate 12-lead ECGs will be taken at screening and at prespecified times on Cycle 1 Days 1 and 2 and Days 15 and 16.

Investigator assessments according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) for solid tumors or the 2007 Revised Response Criteria for Malignant Lymphoma criteria for lymphoma will be applied.

The preliminary anti-tumor activity of AZD5153 in patients with ovarian carcinoma will be evaluated.

Investigator assessments according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) for solid tumors or the 2007 Revised Response Criteria for Malignant Lymphoma criteria for lymphoma will be applied.

The concentration of AZD5153 and its co-former in blood will be determined. Area under the curve is the integral of the concentration-time curve. The area under the plasma drug concentration-time curve (AUC) reflects the actual body exposure to drug after administration. The area under the curve is dependent on the rate of elimination of the drug from the body and the dose administered.

The concentration of AZD5153 and its co-former in blood will be determined. Tmax is the time required after administration for the drug to reach its peak plasma concentration.

The concentration of AZD5153 and its co-former in blood will be determined. Elimination half-life (t1/2) is the time required for the concentration of the drug to reach half of its original value.

The concentration of AZD5153 and its co-former in blood will be determined. Volume of distribution (Vd) is the apparent volume in which a drug is distributed (i.e., the parameter relating drug concentration to drug amount in the body).

The concentration of AZD5153 and its co-former in blood will be determined. Clearance (CL) is the volume of plasma cleared of the drug per unit time.

AstraZeneca

Behaviors and Mental Disorders

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Aggression

Lymphoma, Non-Hodgkin

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Antirheumatic Agents

Amino Acids

Antibodies

Acalabrutinib

Rituximab

Immunoglobulins

Magrolimab

Antineoplastic Agents, Immunological

Immunologic Factors

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Tyrosine

AZD9150 given in combination with acalabrutinib

AZD6738 in combination with acalabrutinib

Hu5F9-G4/rituximab in combination with acalabrutinib

AZD5153 in combination with acalabrutinib

AZD9150 will be administered as a 1-hour intravenous (IV) infusion on Days 1, 3, 5 of Cycle 1, followed by weekly infusions (starting Day 8 of Cycle 1 and beyond).

AZD9150

Acalabrutinib will be administered orally twice daily (bid).

AZD6738 will be administered orally twice daily (bid).

AZD6738

HU5F9-G4 infusions will be given on Weekly (Day 1, 8, 15, and 22) during the first two 28-day cycles, then will be given every two weeks (Day 1 and Day 15) in Cycle 3 and beyond.

Hu5F9-G4

Rituximab infusions will be given Weekly starting on Day 8 (Day 8, 15, and 22) during the first 28-day cycle (4 weeks), then Day 1 of each 4 week cycle for Cycles 2-6. Starting with Cycle 8, Rituximab will be infused on Day 1 of every other cycle (every 8 weeks).

AZD5153 will be administered orally once per day (qd).

Ian Flinn, MD, PhD

This is a Phase 1 platform protocol designed to evaluate various targeted agents for the treatment of relapsed/refractory aggressive Non-Hodgkin's Lymphoma (NHL).

This is a Phase 1 platform protocol designed to evaluate various targeted agents for the treatment of relapsed/refractory aggressive Non-Hodgkin's lymphoma (NHL). Each study arm will be conducted in a predefined disease subset. All study arms are open label and allocation to each study arm will not be randomized.

As this master platform protocol has multiple study arms, subjects can be screened for several study arms at once. Likewise, a subject who ends participation in one study arm may be rescreened for participation in another (separate) study arm.

The primary objective of the study is to evaluate the safety of targeted agents for the treatment of relapsed/refractory aggressive Non-Hodgkin's Lymphoma (NHL). This protocol has a modular design, with the potential for future treatment arms to be added via protocol amendment.

Platform Study for the Treatment of Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma (PRISM Study)

PRISM: A Platform Protocol for the Treatment of Relapsed/Refractory Aggressive Non-Hodgkin's Lymphoma

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

The overall response rate (ORR) is defined as the rate of subjects who achieve either a partial response (PR) or complete response (CR) as assessed by investigators before receiving any other anticancer therapy.

Duration of Response (DOR) is defined as the time from the first objective response of CR or PR to the time of documented disease progression or death due to any cause, whichever occurs first.

Progression free survival (PFS) is defined as the time from first dose date to documented objective disease progression, or death from any cause, whichever occurs first. Disease progression will be determined by the investigators per standard response criteria as outlined in each respective study arm.

Overall Survival (OS) is defined as the time from first dose until the date of death from any cause.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
AZD5153 in Patients With Relapsed or Refractory Solid Tumors, Including Lymphomas	NCT03205176	Malignant Solid... Lymphoma Ovarian Cancer Breast Cancer Pancreatic Canc... Prostate Cancer	AZD5153 Olaparib	18 Years - 130 Years	AstraZeneca
Platform Study for the Treatment of Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma (PRISM Study)	NCT03527147	NHL DLBCL Non-hodgkin's L... Diffuse Large B...	AZD9150 Acalabrutinib AZD6738 Hu5F9-G4 Rituximab AZD5153	18 Years - 130 Years	Acerta Pharma BV

Spots Global Cancer Trial Database for azd5153

Every month we try and update this database with for azd5153 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for azd5153

Every month we try and update this database with for azd5153 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for azd5153 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.