Trial record 1 of 1 for:
NCT04644068
Study of AZD5305 as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Malignancies (PETRA)
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT04644068 |
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Recruitment Status :
Recruiting
First Posted : November 25, 2020
Last Update Posted : April 4, 2024
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Sponsor:
AstraZeneca
Information provided by (Responsible Party):
AstraZeneca
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Brief Summary:
This research is designed to determine if experimental treatment with PARP inhibitor, AZD5305, alone, or in combination with anti-cancer agents is safe, tolerable, and has anti-cancer activity in patients with advanced solid tumors.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Ovarian Cancer Breast Cancer Pancreatic Cancer Prostate Cancer Additional Indications Below for Module 4 and 5 Non-small Cell Lung Cancer Colorectal Cancer Bladder Cancer Gastric Cancer Biliary Cancer Cervical Cancer Endometrial Cancer Small Cell Lung Cancer Only in Module 5 | Drug: AZD5305 Drug: Paclitaxel Drug: Carboplatin Drug: T- Dxd Drug: Dato-DXd Drug: Camizestrant | Phase 1 Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 804 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Sequential Assignment |
| Intervention Model Description: | The study consists of individual modules each evaluating the safety and tolerability of AZD5305 dosed as monotherapy, or with a specific combination partner:
Modules 1 and 4 has 2 study parts: Part A consisting of dose-escalation cohorts and Part B, consisting of expansion cohorts. Modules 2, 3, 5 and 6 have only PART A. |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Modular Phase I/IIa, Open-label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of Ascending Doses of AZD5305 as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Malignancies |
| Actual Study Start Date : | November 12, 2020 |
| Estimated Primary Completion Date : | December 15, 2026 |
| Estimated Study Completion Date : | December 15, 2026 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: Module 1: AZD5305 Monotherapy
AZD5305 Monotherapy
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Drug: AZD5305
Oral PARP inhibitor |
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Experimental: Module 2: AZD5305 + Paclitaxel
AZD5305 + Paclitaxel
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Drug: AZD5305
Oral PARP inhibitor Drug: Paclitaxel IV Anti-microtubule agent |
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Experimental: Module 3: AZD5305 + Carboplatin with or without Paclitaxel
AZD5305 + Carboplatin with or without Paclitaxel
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Drug: AZD5305
Oral PARP inhibitor Drug: Paclitaxel IV Anti-microtubule agent Drug: Carboplatin IV Platinum chemotherapeutic |
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Experimental: Module 4: AZD5305 + Trastuzumab Deruxtecan
AZD5305 + T- DXd
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Drug: AZD5305
Oral PARP inhibitor Drug: T- Dxd IV Antibody-drug conjugate |
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Experimental: Module 5 AZD5305 + Datopotamab Deruxtecan
AZD5305 + Dato-DXd
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Drug: AZD5305
Oral PARP inhibitor Drug: Dato-DXd IV Antibody-drug conjugate |
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Experimental: Module 6 AZD5305 + Camizestrant
AZD5305 + Camizestrant
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Drug: AZD5305
Oral PARP inhibitor Drug: Camizestrant Oral SERD Molecule |
Primary Outcome Measures :
- The number of subjects with adverse events/serious adverse events [ Time Frame: From time of Informed Consent to 28 + 7 days post last dose ( modules 1,2,3,5 and 6). 40+7 days post last dose for Module 4. ]Number of patients with adverse events and with serious adverse events including abnormal clinical observations, abnormal ECG parameters, abnormal laboratory assessments and abnormal vital signs that changed from baseline
- The number of subjects with dose-limiting toxicity (DLT), as defined in the protocol. [ Time Frame: From first dose of study treatment until the end of Cycle 1. ]A DLT is defined as any toxicity that occurs from the first dose of study treatment (either AZD5305 or combination anti-cancer agent) up to and including the planned end of Cycle 1 (the DLT assessment period) that is assessed as unrelated to the disease or disease-related processes under investigation. DLTs occurring outside the DLT window (ie, late onset toxicities) may be defined as a DLT after consultation with the sponsor and investigators, based on the emerging safety profile.
Secondary Outcome Measures :
- Best percentage change in target lesion [ Time Frame: From Screening to confirmed progressive disease (approximately 1 year) ]Change in target lesion size from baseline, as defined by RECIST 1.1.
- Objective Response Rate [ Time Frame: From Screening to confirmed progressive disease (approximately 1 year) ]Best response until progression, as defined by RECIST 1.1.
- Duration of Response [ Time Frame: From Screening to confirmed progressive disease (approximately 1 year) ]Time from first response to progression or death , as defined by RECIST 1.1.
- Progression Free Survival [ Time Frame: From Screening to confirmed progressive disease (approximately 1 year) ]Time from C1D1 to progression or death, as defined by RECIST 1.1.
- Time To Response [ Time Frame: From Screening to confirmed progressive disease (approximately 1 year) ]Time from C1D1 to complete or partial response, as defined by RECIST 1.1.
- Effects of AZD5305 on pH2AX (Ser139) PD biomarker [ Time Frame: From Cycle 0 Day 1 to Cycle 1 Day 15 (approximately 21 days) ]Measure change from baseline in pH2AX
- CA125 response (ovarian cancer) [ Time Frame: From Screening to confirmed progressive disease (approximately 1 year) ]at least a 50% reduction in CA125 levels from a pre-treatment sample as defined by GCIG criteria.
- Module 1: Area Under Curve (AUC) [ Time Frame: At predefined intervals throughout the treatment period (approximately 12 weeks) ]The concentration of AZD5305 in plasma will be determined. Area under the curve is the integral of the concentration-time curve. The AUC reflects the actual body exposure to drug after administration. The AUC is dependent on the rate of elimination of the drug from the body and the dose administered.
- Module 1: Maximum plasma concentration of the drug (Cmax) [ Time Frame: At predefined intervals throughout the treatment period (approximately 12 weeks) ]The concentration of AZD5305 in plasma will be determined (Cmax will be derived).
- Module 1: The time taken to reach the maximum concentration (Tmax) [ Time Frame: At predefined intervals throughout the treatment period (approximately 12 weeks) ]The concentration of AZD5305 in plasma will be determined (Tmax will be derived).
- Module 1 and Module 5: Objective Response Rate (prostate cancer) [ Time Frame: From Screening to confirmed progressive disease (approximately 1 year) ]Best response until progression, as defined by RECIST 1.1 or PCWG3 (bone)
- Module 1: Radiographic progression free survival (prostate cancer) [ Time Frame: From Screening to confirmed progressive disease (approximately 1 year) ]Time from C1D1 to progression or death, as defined by RECIST 1.1 and PCWG3(bone).
- Module 1: Proportion of subjects with ≥ 50% PSA decrease (prostate cancer) [ Time Frame: From Screening to confirmed progressive disease (approximately 1 year) ]PSA from baseline to the lowest post-baseline PSA result, confirmed by a second consecutive PSA assessment
- Module 1 : To investigate the effect of a high-fat meal on the PK of AZD5305 [ Time Frame: Cycle 0, Day 1 (C0D1), in either the "fasted" or "fed" state, followed by a single oral dose of AZD5305 in the other state for Cycle 1, Day 1 (C1D1) at least 72 hours later; 1 cycle is 28 days. ]Effect on High fat meal on PK parameters of AZD5305.PK parameters, including but not limited to AUC and/or AUC(0-t), Cmax, Tmax, AUC(0-t) and Cmax ratio, with and without food
- Module 2: Area Under Curve (AUC) [ Time Frame: At predefined intervals throughout the treatment period (approximately 12 weeks) ]The concentration of AZD5305 in plasma will be determined. Area under the curve is the integral of the concentration-time curve. The AUC reflects the actual body exposure to drug after administration. The AUC is dependent on the rate of elimination of the drug from the body and the dose administered.
- Module 2: Maximum plasma concentration of the drug (Cmax) [ Time Frame: At predefined intervals throughout the treatment period (approximately 12 weeks) ]The concentration of AZD5305 in plasma will be determined (Cmax will be derived).
- Module 2: The time taken to reach the maximum concentration (Tmax) [ Time Frame: At predefined intervals throughout the treatment period (approximately 12 weeks) ]The concentration of AZD5305 in plasma will be determined (Tmax will be derived).
- Module 3: Area Under Curve (AUC) [ Time Frame: At predefined intervals throughout the treatment period (approximately 12 weeks) ]The concentration of AZD5305 in plasma will be determined. Area under the curve is the integral of the concentration-time curve. The AUC reflects the actual body exposure to drug after administration. The AUC is dependent on the rate of elimination of the drug from the body and the dose administered.
- Module 3: Maximum plasma concentration of the drug (Cmax) [ Time Frame: At predefined intervals throughout the treatment period (approximately 12 weeks) ]The concentration of AZD5305 in plasma will be determined (Cmax will be derived).
- Module 3: The time taken to reach the maximum concentration (Tmax) [ Time Frame: At predefined intervals throughout the treatment period (approximately 12 weeks) ]The concentration of AZD5305 in plasma will be determined (Tmax will be derived).
- Module 4 : Area Under Curve [ Time Frame: At predefined intervals throughout the treatment period (approximately 12 weeks) ]The concentration of AZD5305 in plasma will be determined. Area under the curve is the integral of the concentration-time curve. The AUC reflects the actual body exposure to drug after administration. The AUC is dependent on the rate of elimination of the drug from the body and the dose administered.
- Module 4: Maximum plasma concentration of the drug (Cmax) [ Time Frame: At predefined intervals throughout the treatment period (approximately 12 weeks) ]The concentration of AZD5305 in plasma will be determined (Cmax will be derived).
- Module 4: The time taken to reach the maximum concentration (Tmax) [ Time Frame: At predefined intervals throughout the treatment period (approximately 12 weeks) ]The concentration of AZD5305 in plasma will be determined (Tmax will be derived).
- Module 4: Anti-Drug Antibody (ADA) [ Time Frame: Samples will be collected within 1 hour before dose administration on Day 1 of Cycle 1, 2, and 4, then every 4 Cycles (each cycle is 21 days), EoT, and at safety follow-up (40 days after last dose) as per Schedule of Assessments ]To investigate the presence of ADAs for T-DXd
- Module 4: To assess the preliminary anti-tumour activity of AZD5305 as monotherapy and in combination with T-DXd. [ Time Frame: From screening to approximately 6 months ]Time from C1D1 to progression or death, as defined by RECIST v 1.1 summarised at the 6 month landmark (PFS6)
- Module 5: Area Under Curve [ Time Frame: At predefined intervals throughout the treatment period (approximately 12 weeks) ]The concentration of AZD5305 in plasma will be determined. Area under the curve is the integral of the concentration-time curve. The AUC reflects the actual body exposure to drug after administration. The AUC is dependent on the rate of elimination of the drug from the body and the dose administered.
- Module 5: Maximum plasma concentration of the drug (Cmax) [ Time Frame: At predefined intervals throughout the treatment period (approximately 12 weeks) ]The concentration of AZD5305 in plasma will be determined (Cmax will be derived).
- Module 5: The time taken to reach the maximum concentration (Tmax) [ Time Frame: At predefined intervals throughout the treatment period (approximately 12 weeks) ]The concentration of AZD5305 in plasma will be determined (Tmax will be derived).
- Module 5: Anti-Drug Antibody (ADA) [ Time Frame: Whole blood samples for determination of ADA for Dato-DXd in plasma will be collected in patients receiving Dato-DXd per the schedule specified in the SoA : Day 1 of Cycle 1, 2, 4, and 8 (each cycle is 21 days) , EoT, and then 28 day follow up visit. ]Presence of ADAs for Dato-DXd
- Module 5: Premilinary anti tumour activity AZD5305 in combination with [ Time Frame: From screening to confirmed progresive disease ( approximately 12 weeks) ]
objective response rate and radiographic progression-free survival using RECIST v1.1.
Proportion of patients achieving a ≥ 50% decrease in PSA from baseline to the post-baseline PSA result, confirmed by a second consecutive PSA assessment at least 3 weeks later (PSA50 response).
- Module 6: To characterise the PK of AZD5305 and camizestrant following a single dose and at steady state after multiple dosing, when given in combination. [ Time Frame: At predefined interval throughout the treatment (approximately 12 weeks) ]
Plasma concentrations and PK parameters of AZD5305 and camizestrant after single dose and multiple dose administration, including, but not limited to:
AUC, Cmax, Tmax, as data allow
- Module 6: To evaluate the effect of camizestrant on the PK of AZD5305. [ Time Frame: At predefined intervals throughout the treatment period (approximately 12 weeks) ]PK parameters, including but not limited to AUC and/or AUC(0-t), Cmax, Tmax, AUC(0-t) and Cmax ratio, with and without camizestrant.
- Module 6: To evaluate the effect of AZD5305 on the PK of Camizestrant. [ Time Frame: At predefined intervals throughout the treatment period (approximately 12 weeks) ]PK parameters, including but not limited to AUC and/or AUC(0-t), Cmax, Tmax, AUC(0-t) and Cmax ratio, with and without AZD5305.
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years to 130 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Key Inclusion Criteria:
- Age ≥ 18 at the time of screening
- Histological or cytological confirmation of advanced malignancy considered to be suitable for study treatment and meeting module specific eligibility criteria..
- Eastern Cooperative Oncology Group Performance status (ECOG PS: 0-2)
- Life expectancy ≥ 12 weeks
- Progressive cancer at the time of study entry
- Patients must have evaluable disease as defined in module-specific criteria for Part A and Part B
- Adequate organ and marrow function as defined by the protocol.
- For Part B expansion cohorts: Provision of formalin-fixed and paraffin embedded (FFPE) tumour specimen is mandatory, where available, except if stated that it is optional in a specific Module.
For Part A:
- Patients may have received up to one prior line of therapy with a PARPi-based regimen (either as a treatment or as maintenance)
For Part B:
- Patients must not have received prior therapy with a PARPi-based regimen (either as a treatment or as maintenance).
Key Exclusion Criteria:
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Treatment with any of the following:
- Nitrosourea or mitomycin C within 6 weeks of the first dose of study treatment
- Any investigational agents or study drugs from a previous clinical study within 5 half-lives or 3 weeks (whichever is shorter) of the first dose of study treatment
- Any other chemotherapy, immunotherapy or anticancer agents within 3 weeks of the first dose of study treatment
- Any live virus or bacterial vaccine within 28 days of the first dose of study treatment
- Concomitant use of medications or herbal supplements known to be cytochrome P450 3A4 (CYP3A4) strong and moderate inhibitors or inducers.
- Concomitant use of drugs that are known to prolong or shorten QT and have a known risk of Torsades de Pointes.
- Receiving continuous corticosteroids at a dose of >10 mg prednisone/day or equivalent for any reason.
- Major surgery within 4 weeks of the first dose of study treatment.
- Radiotherapy with a wide field of radiation within 4 weeks or radiotherapy with a limited field of radiation for palliation within 2 weeks of the first dose of study treatment.
- Any history of persisting (> 2 weeks) severe pancytopenia due to any cause
- Spinal cord compression or brain metastases unless asymptomatic, treated and stable and not requiring continuous corticosteroids at a dose of >10mg prednisone/day or equivalent for at least 4 weeks prior to start of study treatment. Patients with leptomeningeal carcinomatosis are excluded.
- patient with known predisposition to bleeding (e.g., active peptic ulceration, recent [within 6 months] haemorrhagic stroke, proliferative diabetic retinopathy).
- Cardiac conditions as defined by the clinical study protocol
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Other cardiovascular diseases as defined by any of the following:
- Symptomatic heart failure,
- uncontrolled hypertension,
- hypertensive heart disease with significant left ventricular hypertrophy
- acute coronary syndrome (ACS)/acute myocardial infarction (AMI), unstable angina pectoris, coronary intervention procedure with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) within 6 months.
- cardiomyopathy of any etiology
- presence of clinically significant valvular heart disease
- history of atrial or ventricular arrhythmia requiring treatment; subjects with atrial fibrillation and optimally controlled ventricular rate (< 100 beats per minute) are permitted.
- subjects with atrial fibrillation and optimally controlled ventricular rate are permitted
- transient ischaemic attack, or stroke within 6 months prior to screening
- patients with symptomatic hypotension at screening
- Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML).
- Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of AZD5305
- Known allergy or hypersensitivity to investigational product(s) or any of the excipients of the investigational product(s).
Prior malignancy whose natural history, in the Investigator's opinion, has the potential to interfere with safety and efficacy assessments of the investigational regimen.
other module-specific criteria may apply
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04644068
Contacts
| Contact: AstraZeneca Clinical Study Information Center | 1-877-240-9479 | information.center@astrazeneca.com | |
| Contact: AZ Breast Cancer Study Navigators | +1-877-400-4656 | AstraZeneca@CareboxHealth.com |
Locations
Show 74 study locations
Sponsors and Collaborators
AstraZeneca
Investigators
| Principal Investigator: | Timothy Yap | M.D. Anderson Cancer Center |
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | AstraZeneca |
| ClinicalTrials.gov Identifier: | NCT04644068 |
| Other Study ID Numbers: |
D9720C00001 2020-002688-77 ( EudraCT Number ) |
| First Posted: | November 25, 2020 Key Record Dates |
| Last Update Posted: | April 4, 2024 |
| Last Verified: | April 2024 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by AstraZeneca:
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PARP inhibitor Breast Cancer Pancreatic Cancer |
Prostate Cancer Ovarian Cancer AZD5305, T-DXd, Enhertu, Trastuzumab Deruxtecan, Dato-DXd, Datopotamab Deruxtecan, Camizestrant |
Additional relevant MeSH terms:
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Lung Neoplasms Prostatic Neoplasms Pancreatic Neoplasms Ovarian Neoplasms Small Cell Lung Carcinoma Endometrial Neoplasms Neoplasms by Site Neoplasms Respiratory Tract Neoplasms Thoracic Neoplasms Lung Diseases Respiratory Tract Diseases Genital Neoplasms, Male Urogenital Neoplasms Genital Diseases, Male |
Genital Diseases Urogenital Diseases Prostatic Diseases Male Urogenital Diseases Carcinoma, Bronchogenic Bronchial Neoplasms Digestive System Neoplasms Digestive System Diseases Endocrine Gland Neoplasms Pancreatic Diseases Endocrine System Diseases Ovarian Diseases Adnexal Diseases Genital Diseases, Female Female Urogenital Diseases |