Ignite Creation Date:
2025-12-24 @ 12:09 PM
Ignite Modification Date:
2025-12-27 @ 10:37 PM
Study NCT ID:
NCT03772561
Status:
RECRUITING
Last Update Posted:
2025-07-22
First Post:
2018-12-10
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Phase I Study of AZD5363 + Olaparib + Durvalumab in Patients With Advanced or Metastatic Solid Tumor Malignancies
Sponsor:
National University Hospital, Singapore
Organization:
Study Overview
Official Title:
An Investigator Sponsored Phase I Study of the Safety, Tolerability and Pharmacodynamics of Escalating Doses of Combination Treatment of AZD5363 + Olaparib + Durvalumab (MEDI4736) in Patients With Advanced or Metastatic Solid Tumor Malignancies.
Status:
RECRUITING
Status Verified Date:
2025-07
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:
MEDIPAC
Brief Summary:
This is a Phase 1 dose-escalation study to evaluate the safety and tolerability of combination treatment of AZD5363 + Olaparib + Durvalumab and to determine the RP2D in patients with advanced or metastatic solid tumor malignancies.
The purpose of this trial is to determine if combination treatment of drugs, Olaparib, AZD5363 and Durvalumab has beneficial effects in advanced or metastatic cancers and to determine the effects it has on patients and their cancer.
Primary Objectives
• To evaluate the safety and tolerability of combination treatment AZD5363 + Olaparib + Durvalumab and determine the Maximum Tolerated Dose (MTD), Dose-Limiting Toxicities (DLTs), and Recommended Phase 2 Dose (RP2D) for patients with advanced or metastatic solid tumor malignancies.
Secondary Objectives
* To determine the pharmacodynamics (PDn) of combination treatment AZD5363 + Olaparib + Durvalumab in patients with advanced or metastatic solid tumor malignancies
* To describe anti-tumor response using immune RECIST of combination treatment AZD5363 + Olaparib + Durvalumab in patients with advanced or metastatic solid tumor malignancies
Exploratory Objectives
* To evaluate anti-tumour response using RECIST v1.1 for combination treatment AZD5363 + Olaparib + Durvalumab in patients with advanced or metastatic solid tumor malignancies
* To explore molecular correlates of the relationship between mutations in Akt/ PIK3CA/PTEN pathway and response to AZD5363 +Olaparib+ Durvalumab
* To understand the role of tumour microenvironment in regulation of intratumoral immune regulators (i.e. T-regulatory cells) in improving response to Durvalumab
* To understand the role of AZD5363 as an immunomodulator
* To evaluate the role of PD-1 and PDL-1 immunohistochemical and tumour MMR status in predicting response to immune check point inhibitors.
The purpose of this trial is to determine if combination treatment of drugs, Olaparib, AZD5363 and Durvalumab has beneficial effects in advanced or metastatic cancers and to determine the effects it has on patients and their cancer.
Primary Objectives
• To evaluate the safety and tolerability of combination treatment AZD5363 + Olaparib + Durvalumab and determine the Maximum Tolerated Dose (MTD), Dose-Limiting Toxicities (DLTs), and Recommended Phase 2 Dose (RP2D) for patients with advanced or metastatic solid tumor malignancies.
Secondary Objectives
* To determine the pharmacodynamics (PDn) of combination treatment AZD5363 + Olaparib + Durvalumab in patients with advanced or metastatic solid tumor malignancies
* To describe anti-tumor response using immune RECIST of combination treatment AZD5363 + Olaparib + Durvalumab in patients with advanced or metastatic solid tumor malignancies
Exploratory Objectives
* To evaluate anti-tumour response using RECIST v1.1 for combination treatment AZD5363 + Olaparib + Durvalumab in patients with advanced or metastatic solid tumor malignancies
* To explore molecular correlates of the relationship between mutations in Akt/ PIK3CA/PTEN pathway and response to AZD5363 +Olaparib+ Durvalumab
* To understand the role of tumour microenvironment in regulation of intratumoral immune regulators (i.e. T-regulatory cells) in improving response to Durvalumab
* To understand the role of AZD5363 as an immunomodulator
* To evaluate the role of PD-1 and PDL-1 immunohistochemical and tumour MMR status in predicting response to immune check point inhibitors.
Detailed Description:
This study is divided into 3 different periods: Screening, Treatment, and End of Treatment Before taking the treatment, patients will have some tests and procedures done to make sure they are eligible for the study (Screening). Then they will enter the Treatment period, where Durvalumab, Olaparib and AZD5363 will be administered to them. If they stop taking your study medication for any reason, an End of Treatment visit will be conducted within 30 days after the last doze of study medication.
Screening Assessment:
* Written Informed Consent
* Inclusion/Exclusion Criteria
* Complete Medical History
* Prior therapies and PFS on last anti-cancer therapy
* Complete Physical Examination amp; ECOG
* Standard Clinical Neurologic Examination
* BSA
* Weight
* Blood Pressure, Pulse and Temperature
* Oxygen Saturation (Pulse Oximetry)
* 12-lead Electrocardiogram
* HbA1c and fasting glucose
* Serum Chemistry (renal panel 2) amp; Serum Troponin Level
* Amylase and lipase
* Liver function test
* Serum Pregnancy Test (for women of childbearing potential)
* Thyroid function test including TSH and free T4
* Coagulation Parameters
* Chest X-ray (if clinically indicated)
* CBC with Differential
* CT or MRI Scan Tumor Measurement
* PET-CT/PET-MRI Scan Tumor Measurement (optional)
* Transthoracic Echo/ MUGA
* Baseline Symptoms
* Concomitant Medication Assessments
* Tumor Biopsy
* Fasting lipids
* Assessment for hepatitis B surface antigen, hepatitis C antibodies and HIV antibodies
* Urinalysis
Run-in Period (Day -14 until Day 0)
* Complete or Symptom Directed Physical Examination amp; ECOG
* Standard Clinical Neurologic Examination
* BSA
* Weight
* Blood Pressure, Pulse and Temperature
* 12-lead Electrocardiogram
* Serum Chemistry (renal panel 2)
* Serum Troponin Level
* Coagulation Parameters
* Liver panel including amylase and lipase
* CBC with Differential
* Oxygen Saturation (Pulse Oximetry)
* Drug Administration only for AZD5363
* Pharmacodynamics (PDn) blood
* AE Assessments
* Concomitant Medication Assessments
Cycle 1 (every week)
* Complete or Symptom Directed Physical Examination amp; ECOG
* Standard Clinical Neurologic Examination
* BSA
* Weight
* Blood Pressure, Pulse and Temperature
* HbA1c ( To be performed on cycle 1 day 1and every 12 week thereafter)
* 12-lead Electrocardiogram
* Serum Chemistry (renal panel 2)
* Serum Troponin Level
* Coagulation Parameters
* Liver panel including amylase and lipase
* CBC with Differential
* Thyroid Stimulating Hormone (TSH), ACTH (only every 4 weeks, D1 of every cycle)
* Oxygen Saturation (Pulse Oximetry)
* Drug Administration
* Pharmacodynamics (PDn)
* AE Assessments
* Concomitant Medication Assessments
* Urinalysis
Cycle 2 and Cycle 3 (every 2 weeks)
* Complete or Symptom Directed Physical Examination amp; ECOG
* Standard Clinical Neurologic Examination
* BSA
* Weight
* Blood Pressure, Pulse and Temperature
* 12-lead Electrocardiogram
* Serum Chemistry (renal panel 2)
* Liver panel including amylase and lipase
* Serum Troponin Level
* Coagulation Parameters
* CBC with Differential
* Oxygen Saturation (Pulse Oximetry)
* Drug Administration
* Pharmacodynamics (PDn) blood (Cycle 2 Day 1)
* AE Assessments
* \*CT or MRI Scan Tumor Measurement (end of Cycle 2every 8 weeks in the last week of the cycle)
* Concomitant Medication Assessments
* Fasting lipids
* Urinalysis
* Transthoracic Echo/ MUGA (only if indicated)
Cycle 4 and Beyond (every 4 weeks)
* Complete or Symptom Directed Physical Examination amp; ECOG
* Weight
* Blood Pressure, Pulse and Temperature
* Standard Clinical Neurologic Examination
* Oxygen Saturation (Pulse Oximetry)
* 12-lead Electrocardiogram
* Transthoracic Echo/ MUGA (only at C4D1)
* Fasting lipids
* Serum Chemistry (renal panel 2)
* Serum Troponin Level
* Thyroid Stimulating Hormone (TSH), ACTH
* Coagulation Parameters
* CBC with Differential
* \*CT or MRI Scan Tumor Measurement (end of Cycle 4 and every 8 weeks thereafter)
* Drug Administration
* \*PET-CT/PET-MRI Scan Tumor Measurement (optional) (every 8 weeks)
* AE Assessments
* Concomitant Medication Assessments
* Transthoracic Echo/ MUGA (only if indicated)
Final Visit
* Complete Physical Examination amp; ECOG
* Weight
* Blood Pressure, Pulse and Temperature
* Standard Clinical Neurologic Examination
* Oxygen Saturation (Pulse Oximetry)
* 12-lead Electrocardiogram and troponin level
* Transthoracic Echo/ MUGA
* Fasting lipids
* Serum Chemistry
* Coagulation Parameters
* CBC with Differential
* Thyroid Stimulating Hormone (TSH)
* AE assessments
* Concomitant Medication Assessment
Screening Assessment:
* Written Informed Consent
* Inclusion/Exclusion Criteria
* Complete Medical History
* Prior therapies and PFS on last anti-cancer therapy
* Complete Physical Examination amp; ECOG
* Standard Clinical Neurologic Examination
* BSA
* Weight
* Blood Pressure, Pulse and Temperature
* Oxygen Saturation (Pulse Oximetry)
* 12-lead Electrocardiogram
* HbA1c and fasting glucose
* Serum Chemistry (renal panel 2) amp; Serum Troponin Level
* Amylase and lipase
* Liver function test
* Serum Pregnancy Test (for women of childbearing potential)
* Thyroid function test including TSH and free T4
* Coagulation Parameters
* Chest X-ray (if clinically indicated)
* CBC with Differential
* CT or MRI Scan Tumor Measurement
* PET-CT/PET-MRI Scan Tumor Measurement (optional)
* Transthoracic Echo/ MUGA
* Baseline Symptoms
* Concomitant Medication Assessments
* Tumor Biopsy
* Fasting lipids
* Assessment for hepatitis B surface antigen, hepatitis C antibodies and HIV antibodies
* Urinalysis
Run-in Period (Day -14 until Day 0)
* Complete or Symptom Directed Physical Examination amp; ECOG
* Standard Clinical Neurologic Examination
* BSA
* Weight
* Blood Pressure, Pulse and Temperature
* 12-lead Electrocardiogram
* Serum Chemistry (renal panel 2)
* Serum Troponin Level
* Coagulation Parameters
* Liver panel including amylase and lipase
* CBC with Differential
* Oxygen Saturation (Pulse Oximetry)
* Drug Administration only for AZD5363
* Pharmacodynamics (PDn) blood
* AE Assessments
* Concomitant Medication Assessments
Cycle 1 (every week)
* Complete or Symptom Directed Physical Examination amp; ECOG
* Standard Clinical Neurologic Examination
* BSA
* Weight
* Blood Pressure, Pulse and Temperature
* HbA1c ( To be performed on cycle 1 day 1and every 12 week thereafter)
* 12-lead Electrocardiogram
* Serum Chemistry (renal panel 2)
* Serum Troponin Level
* Coagulation Parameters
* Liver panel including amylase and lipase
* CBC with Differential
* Thyroid Stimulating Hormone (TSH), ACTH (only every 4 weeks, D1 of every cycle)
* Oxygen Saturation (Pulse Oximetry)
* Drug Administration
* Pharmacodynamics (PDn)
* AE Assessments
* Concomitant Medication Assessments
* Urinalysis
Cycle 2 and Cycle 3 (every 2 weeks)
* Complete or Symptom Directed Physical Examination amp; ECOG
* Standard Clinical Neurologic Examination
* BSA
* Weight
* Blood Pressure, Pulse and Temperature
* 12-lead Electrocardiogram
* Serum Chemistry (renal panel 2)
* Liver panel including amylase and lipase
* Serum Troponin Level
* Coagulation Parameters
* CBC with Differential
* Oxygen Saturation (Pulse Oximetry)
* Drug Administration
* Pharmacodynamics (PDn) blood (Cycle 2 Day 1)
* AE Assessments
* \*CT or MRI Scan Tumor Measurement (end of Cycle 2every 8 weeks in the last week of the cycle)
* Concomitant Medication Assessments
* Fasting lipids
* Urinalysis
* Transthoracic Echo/ MUGA (only if indicated)
Cycle 4 and Beyond (every 4 weeks)
* Complete or Symptom Directed Physical Examination amp; ECOG
* Weight
* Blood Pressure, Pulse and Temperature
* Standard Clinical Neurologic Examination
* Oxygen Saturation (Pulse Oximetry)
* 12-lead Electrocardiogram
* Transthoracic Echo/ MUGA (only at C4D1)
* Fasting lipids
* Serum Chemistry (renal panel 2)
* Serum Troponin Level
* Thyroid Stimulating Hormone (TSH), ACTH
* Coagulation Parameters
* CBC with Differential
* \*CT or MRI Scan Tumor Measurement (end of Cycle 4 and every 8 weeks thereafter)
* Drug Administration
* \*PET-CT/PET-MRI Scan Tumor Measurement (optional) (every 8 weeks)
* AE Assessments
* Concomitant Medication Assessments
* Transthoracic Echo/ MUGA (only if indicated)
Final Visit
* Complete Physical Examination amp; ECOG
* Weight
* Blood Pressure, Pulse and Temperature
* Standard Clinical Neurologic Examination
* Oxygen Saturation (Pulse Oximetry)
* 12-lead Electrocardiogram and troponin level
* Transthoracic Echo/ MUGA
* Fasting lipids
* Serum Chemistry
* Coagulation Parameters
* CBC with Differential
* Thyroid Stimulating Hormone (TSH)
* AE assessments
* Concomitant Medication Assessment
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 2018/00137 | OTHER | NHG Domain Specific Research Board | View |