Ignite Creation Date:
2024-05-06 @ 10:14 AM
Last Modification Date:
2024-10-26 @ 12:27 PM
Study NCT ID:
NCT03205176
Status:
COMPLETED
Last Update Posted:
2021-05-06
First Post:
2017-06-23
Brief Title:
AZD5153 in Patients With Relapsed or Refractory Solid Tumors Including Lymphomas
Sponsor:
AstraZeneca
Organization:
AstraZeneca
Study Overview
Official Title:
A Phase I Multicenter Dose-Escalation Study to Assess the Tolerability Pharmacokinetics and Preliminary Anti-tumor Activity of AZD5153 in Patients With RelapsedRefractory Malignant Solid Tumors Including Lymphomas
Status:
COMPLETED
Status Verified Date:
2021-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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
Detailed Description:
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 wont exceed the total dose per cycle that has been shown to be safe and tolerated as a monotherapy and wont 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 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 wont exceed the total dose per cycle that has been shown to be safe and tolerated as a monotherapy and wont 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| REFMAL 495 | OTHER | Sarah Cannon Development Innovations LLC | None |