Progressive Metastatic Castrate-Resistant Prostate CancerPhase 2AARDVARCNCT04495179
A Study of AZD4635 With Durvalumab and With Cabazitaxel and Durvalumab in Patients With mCRPC.
A Phase 2 study testing AZD4635, Durvalumab and Cabazitaxel in people with Progressive Metastatic Castrate-Resistant Prostate Cancer, run by AstraZeneca at 16 sites in 5 countries.
Trial summary
This is a Phase II, international, open-label, two-arm, non-randomised study of AZD4635 in participants with metastatic castration-resistant prostate cancer (mCRPC). Read more about this study
- Who is it for?
- Ages 18 to 150 years, men only
- Conditions the study is for
- Progressive Metastatic Castrate-Resistant Prostate Cancer
- What is being tested?
- AZD4635, Durvalumab and Cabazitaxel
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 16 sitesin 5 countries
- Study dates
- 4 Aug 2020to 8 Aug 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 150 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed adenocarcinoma of the prostate.
- Known castrate-resistant disease.
- Evidence of disease progression ≤6 months.
- Body weight >30 kg at screening.
- Willingness to adhere to the study treatment-specific contraception requirements.
- Adequate bone marrow reserve and organ function.
Show all 27Show fewer
- Adequate organ function for Arm A as demonstrated by all of the following laboratory values:
- Alanine aminotransferase (ALT) ≤2.5 × upper limit of normal (ULN) if no demonstrable liver metastases or ≤5 × ULN in the presence of liver metastases.
- Aspartate aminotransferase (AST) ≤2.5 × ULN if no demonstrable liver metastases or ≤5 × ULN in the presence of liver metastases
- Total bilirubin (TBL) ≤1.5 × ULN
- TBL ≤2.0 × ULN in the case of known Gilbert syndrome with normal direct bilirubin
- Participants in Arm A must have received the following prior therapy:
- Maximum of 3 lines of therapy in the mCRPC setting
- Prior therapy with one or more NHAs (eg, abiraterone acetate, enzalutamide, apalutamide, darolutamide) in either hormone-sensitive or hormone-refractory settings
- Prior therapy with one or more lines of taxanes (eg, docetaxel and/or cabazitaxel)
- Alternatively, must be taxane-ineligible
- Prior therapy can be in either the hormone-sensitive or the hormone-refractory setting
- Adequate organ function for Arm B as demonstrated by all of the following laboratory values:
- AST and/or ALT ≤1.5 × ULN
- TBL ≤ ULN
- TBL ≤2.0 × ULN in the case of known Gilbert syndrome with normal direct bilirubin
- Participants in Arm B must have received the following prior therapy:
- Prior docetaxel (taxane) in either hormone-sensitive or hormone-refractory settings
- Received no prior cytotoxic chemotherapy other than docetaxel for prostate cancer except for estramustine and except adjuvant/neo-adjuvant treatment completed >3 years ago.
- Prior therapy with only one NHAs (eg, abiraterone acetate or enzalutamide; prior apalutamide is not permitted) for treatment of mCRPC in either hormone-sensitive or hormone-refractory settings.
- Be suitable to receive concomitant Granulocyte-colony stimulating factor during all cycles of cabazitaxel.
- Participants who meet inclusion criteria for Arm B will be allocated preferentially to that arm until recruitment to that arm is completed.
Who cannot join
- Active brain metastases or leptomeningeal metastases.
- There must be no requirement for immunosuppressive doses of systemic corticosteroids for at least 2 weeks prior to study enrollment.
- History of pneumonitis requiring corticosteroids, second malignancy that is progressing and/or received active treatment ≤3 years before the first dose of study intervention, and hypersensitivity to polysorbate-80 if allocated to cabazitaxel.
- As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases.
- Creatinine clearance <40 mL/min (calculated by Cockcroft-Gault equation).
- Prior exposure to immune-mediated therapy including.
- Ongoing treatment with warfarin (Coumadin).
- Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study intervention.
Trial locations and contacts
16 sites in 5 countries.
16 sites in 5 countries
United States5 sites
Research Site
Atlanta, Georgia, 30318
Research Site
Sacramento, California, 95817
Research Site
St Louis, Missouri, 63110
Research Site
Tampa, Florida, 33612
Research Site
Winston-Salem, North Carolina, 27157
Spain4 sites
Research Site
Barcelona, 08041
Research Site
Barcelona, 8035
Research Site
Hospitalet deLlobregat, 08907
Research Site
Madrid, 28034
South Korea3 sites
Research Site
Goyang-si, 10408
Research Site
Seoul, 06351
Research Site
Seoul, 06591
About this study
Official title: A Phase II, Open-label, Study to Assess the Efficacy, Safety, and Tolerability of AZD4635 in Combination With Durvalumab and in Combination With Cabazitaxel and Durvalumab in Patients Who Have Progressive Metastatic Castrate-Resistant Prostate Cancer (AARDVARC)
This is a Phase II, international, open-label, two-arm, non-randomised study of AZD4635 in participants with metastatic castration-resistant prostate cancer (mCRPC).
Read the detailed description
This is a Phase II, international, open-label, two-arm, non-randomised study of AZD4635 in participants with mCRPC. Participants in each arm will be stratified by the presence of measurable soft tissue metastasis (per Response Evaluation Criteria in Solid Tumours [RECIST v1.1]) or bone-only metastasis (per Prostate Cancer Working Group 3 [PCWG3 criteria]). There will be no formal comparisons between treatment arms.
AZD4635 plus durvalumab (Arm A) will consist of 80 participants with mCRPC previously treated with one or more approved new hormonal agent(s) (NHAs) and one or more taxanes or participants who are taxane ineligible.
AZD4635 plus durvalumab plus cabazitaxel (Arm B) will consist of 80 participants mCRPC previously treated with docetaxel and one prior NHA.
As of November 2020, the Sponsor stopped enrolment in Arm A following decisions at the program level, not related to any safety issues. Ongoing participants in Arm A may continue treatment as planned.
- Being tested
- AZD4635, Durvalumab, Cabazitaxel
- Keywords
- Prostate Cancer
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD4635Drug
Subjects will receive AZD4635 orally daily
DurvalumabDrug
Subjects will receive intravenous durvalumab every 4 weeks for Arm A and every 3 weeks for Arm B.
CabazitaxelDrug
Subjects will receive intravenous cabazitaxel every 3 weeks
| Study group | Role | What they receive |
|---|---|---|
| Arm A: AZD4635 + durvalumab | Experimental | AZD4635 plus durvalumab (Arm A) will consist of participants with mCRPC previously treated with one or more approved NHAs (eg, abiraterone acetate, enzalutamide, apalutamide and/or darolutamide), and one or more taxanes, or participants who are taxane ineligible. Receives: Drug: AZD4635; Drug: Durvalumab |
| Arm B: AZD4635 + durvalumab + cabazitaxel | Experimental | AZD4635 plus durvalumab plus cabazitaxel (Arm B) will consist of participants with mCRPC previously treated with docetaxel and one prior NHA (either abiraterone acetate or enzalutamide but not both (prior apalutamide is not allowed in Arm B). Receives: Drug: AZD4635; Drug: Durvalumab; Drug: Cabazitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Radiographic Progression Free Survival (rPFS) in Each Arm Separately to Determine the Efficacy of AZD4635 Plus Durvalumab and of AZD4635 Plus Durvalumab Plus Cabazitaxel in Patients With Metastatic Castrate-resistant Prostate Cancer (mCRPC)
rPFS was defined as the time from first dose to radiographic progression, assessed by the Investigator per RECIST 1.1 (soft tissue) and PCWG3 (Prostate Cancer Working Group 3) criteria [bone] or death from any cause, whichever occurred first.
Measured: From first dose to first documented progression or death from any cause (whichever comes first) (approximately 1 year)
Secondary outcomes (16)
rPFS by Adenosine (ADO) Signalling Gene Expression in High and Low Subgroups to Determine the Efficacy of AZD4635 Plus Durvalumab Plus Cabazitaxel in Participants With mCRPC
rPFS was defined as the time from first dose to radiographic progression, assessed by the Investigator per RECIST 1.1 (soft tissue) and PCWG3 criteria (bone) or death from any cause, whichever occurred first.
Measured: From first dose to first documented progression or death from any cause (whichever comes first), up to two years
Overall Survival (OS) in Each Arm Separately to Determine the Efficacy of AZD4635 Plus Durvalumab and of AZD4635 Plus Durvalumab Plus Cabazitaxel in Participants With mCRPC
OS was defined as the time from first dose until death due to any cause regardless of whether the participant withdrew from study treatment or received another anti-cancer therapy.
Measured: Arm A and B: Every 90 days from the last dose of study drug up to 2 years
Number of Participants With Objective Response in Subjects With MCRPC Who Received AZD4635 Plus Durvalumab Plus Cabazitaxel
Confirmed ORR was defined as the proportion of participants with a confirmed complete response (CR) or partial response (PR) using overall radiographic response assessed by RECIST v1.1 and PCWG-3 criteria (bone), and was based on a subset of all treated participants with measurable disease at baseline per the site Investigator.
Measured: From first dose to first documented progression or death from any cause (whichever comes first), up to two years
Number of Participants With Prostate-specifin Antigen (PSA50) Response in Subjects With MCRPC Who Received AZD4635 Plus Durvalumab Plus Cabazitaxel
Confirmed PSA50 response is defined as the proportion of participants who achieved a ≥50% decrease in PSA from baseline to the lowest post-baseline PSA, confirmed by a consecutive PSA at least 3 weeks later and was based on PSA evaluable participants (dosed participants with an abnormal baseline PSA [≥1 ng/mL]).
Measured: Arm A: Screening, Day 1 of each cycle up to 11 months (Each cycle was 28 days in length); Arm B: Screening, Day 1 of each cycle up to 11 months (Cycle 1 to Cycle 10 = 21 days, Cycle 11 onwards = 28 days)
Change From Baseline in Worst Pain in the Daily Activities Scales of the Brief Pain Inventory - Short Form (BPI-SF)
"Worst pain" and "Average pain" are 'single question' scores from the BPI short form and may take any value from 0 to 10 (worst outcome). "Interference Pain" is the total score of 7 sub-scores, where each value may take any value from 0 to 10 (worst outcome). The range of the "Interference Score" can be from 0 to 70.
Measured: Arm A: Screening, Day 1 of each cycle up to 9 months (Each cycle was 28 days in length); Arm B: Screening, Day 1 of each cycle up to 9 months (Each cycle was 21 days in length)
Change From Baseline in Average Pain in the Daily Activities Scales of the Brief Pain Inventory - Short Form (BPI-SF)
"Worst pain" and "Average pain" are 'single question' scores from the BPI short form and may take any value from 0 to 10 (worst outcome). "Interference Pain" is the total score of 7 sub-scores, where each value may take any value from 0 to 10 (worst outcome). The range of the "Interference Score" can be from 0 to 70.
Measured: Arm A: Screening, Day 1 of each cycle up to 9 months (Each cycle was 28 days in length); Arm B: Screening, Day 1 of each cycle up to 9 months (Each cycle was 21 days in length)
Change From Baseline in Pain Interference in the Daily Activities Scales of the Brief Pain Inventory - Short Form (BPI-SF)
"Worst pain" and "Average pain" are 'single question' scores from the BPI short form and may take any value from 0 to 10 (worst outcome). "Interference Pain" is the total score of 7 sub-scores, where each value may take any value from 0 to 10 (worst outcome). The range of the "Interference Score" can be from 0 to 70.
Measured: Arm A: Screening, Day 1 of each cycle up to 9 months (Each cycle was 28 days in length); Arm B: Screening, Day 1 of each cycle up to 9 months (Each cycle was 21 days in length)
Number of Participants Who Progressed Based on BPI-SF Item 3
Pain progression was assessed using BPI-SF.
Measured: Arm A: Screening, Day 1 of each cycle up to 12 months (Each cycle was 28 days in length); Arm B: Screening, Day 1 of each cycle up to 12 months (Cycle 1 to Cycle 10 = 21 days, Cycle 11 onwards = 28 days)
Change From Baseline in the FACT Advanced Prostate Symptom Indext-6 (FAPSI-6), as Derived From 6 Items, the FAPSI-8 From 8 Items Within the FACT-P and the Prostate Cancer Symptoms (PCS), From the 12 Items in the Prostrate-specific Module of the FACT-P
The Functional Assessment of Cancer Therapy-Prostate (FACT-P) will be used to measure health related quality of life (HRQL) in men with prostate cancer. It consists of 4 subscales (physical, emotional, functional and social/family well-being) plus a 12-item prostate-specific module, the PCS subscale, which highlights concerns specific to participants with prostate cancer. FAPSI-6 is defined as a symptom score made up of 6 items from within the FACT-P (pain [n = 3], fatigue [n = 1], weight loss [n = 1], and concerns about the condition getting worse [n = 1]). Each question in the FACT-P questionnaires has a choice of 5 responses, "Not at all", "A little bit", "Somewhat", "Quite a bit" and "Very much". The scores range from 0 ("Not at all") to 4 ("Very much") for positively phrased questions. Negatively phrased questions have a reverse scoring, from 0 ("Very much") to 4 ("Not at all"). This results in a consistent approach, where higher scores indicate a better quality of life.
Measured: Arm A: Screening, Day 1 of each cycle up to 9 months (Each cycle was 28 days in length); Arm B: Screening, Day 1 of each cycle up to 9 months (Each cycle was 21 days in length)
Maximum Observed Plasma Concentration (Cmax)
Investigate the PK of AZD4635 when given in combination with durvalumab, and when given in combination with durvalumab plus cabazitaxel.
Measured: Arm A:Cycle 1 to 3, and Cycle 4 onwards, and 90-day follow-up (FU) visit up to 14 months [Each cycle was 28 days in length];Arm B: Cycle 1 to 7 and Cycle 11 onwards, and 90-day FU up to 14 months (Cycle 1 to Cycle 10 = 21 days, Cycle 11 onwards = 28 days)
Terminal Half-life (t1/2λz)
Investigated the PK of AZD4635 when given in combination with durvalumab, and when given in combination with durvalumab plus cabazitaxel.
Measured: Arm A:Cycle 1 to 3, and Cycle 4 onwards, and 90-day follow-up (FU) visit up to 14 months [Each cycle was 28 days in length];Arm B: Cycle 1 to 7 and Cycle 11 onwards, and 90-day FU up to 14 months (Cycle 1 to Cycle 10 = 21 days, Cycle 11 onwards = 28 days)
Area Under the Plasma Concentration Time Curve From Zero to the Time of the Last Measurable Concentration (AUClast)
Investigated the PK of AZD4635 when given in combination with durvalumab, and when given in combination with durvalumab plus cabazitaxel.
Measured: Arm A:Cycle 1 to 3, and Cycle 4 onwards, and 90-day follow-up (FU) visit up to 14 months [Each cycle was 28 days in length];Arm B: Cycle 1 to 7 and Cycle 11 onwards, and 90-day FU up to 14 months (Cycle 1 to Cycle 10 = 21 days, Cycle 11 onwards = 28 days)
Area Under the Plasma Concentration Time Curve From Zero to 24 Hours [AUC(0-24)]
Investigated the PK of AZD4635 when given in combination with durvalumab, and when given in combination with durvalumab plus cabazitaxel.
Measured: Arm A:Cycle 1 to 3, and Cycle 4 onwards, and 90-day follow-up (FU) visit up to 14 months [Each cycle was 28 days in length];Arm B: Cycle 1 to 7 and Cycle 11 onwards, and 90-day FU up to 14 months (Cycle 1 to Cycle 10 = 21 days, Cycle 11 onwards = 28 days)
Area Under the Plasma Concentration Time Curve From Zero Extrapolated to Infinity (AUCinf)
Investigated the PK of AZD4635 when given in combination with durvalumab, and when given in combination with durvalumab plus cabazitaxel.
Measured: Arm A:Cycle 1 to 3, and Cycle 4 onwards, and 90-day follow-up (FU) visit up to 14 months [Each cycle was 28 days in length];Arm B: Cycle 1 to 7 and Cycle 11 onwards, and 90-day FU up to 14 months (Cycle 1 to Cycle 10 = 21 days, Cycle 11 onwards = 28 days)
Apparent Volume of Distribution During the Terminal Phase (Vz/F)
Investigated the PK of AZD4635 when given in combination with durvalumab, and when given in combination with durvalumab plus cabazitaxel.
Measured: Arm A:Cycle 1 to 3, and Cycle 4 onwards, and 90-day follow-up (FU) visit up to 14 months [Each cycle was 28 days in length];Arm B: Cycle 1 to 7 and Cycle 11 onwards, and 90-day FU up to 14 months (Cycle 1 to Cycle 10 = 21 days, Cycle 11 onwards = 28 days)
Number of Subjects With Serious and Non-serious Adverse Events
Safety and tolerability of each treatment regimen were assessed in participants with mCRPC.
Measured: Arm A: From Screening up to 14 months (Each cycle was 28 days in length); Arm B: From Screening up to 14 months (Cycle 1 to Cycle 10 was 21 days in length, and Cycle 11 onwards was 28 days in length)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2020
- Study start4 Aug 2020
- Primary completion1 Nov 2021
- Study completion8 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Progressive Metastatic Castrate-Resistant Prostate CancerStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Parexel
- Responsible party
- Sponsor
- Investigators
- Christopher J Sweeney, MBBS, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04495179
- Sponsor's protocol ID
- D8731C00002
- Other IDs
- 2020-000209-10
- Acronym
- AARDVARC
- Status last verified
- Jul 2023
- First submitted
- 23 Jul 2020
- Last updated
- 9 Aug 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Open-label, Study to Assess the Efficacy, Safety, and Tolerability of AZD4635 in Combination With Durvalumab and in Combination With Cabazitaxel and Durvalumab in Patients Who Have Progressive Metastatic Castrate-Resistant Prostate Cancer (AARDVARC)
- ClinicalTrials.gov ID
- NCT04495179
- Acronym / sponsor ID
- AARDVARC / D8731C00002
- Keywords
- Prostate Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Parexel
- Study start
- 4 Aug 2020 (actual)
- Primary completion
- 1 Nov 2021 (actual)
- Study completion
- 8 Aug 2022 (actual)
- First posted
- 31 Jul 2020 (actual)
- Results
- Posted 9 Aug 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase II, international, open-label, two-arm, non-randomised study of AZD4635 in participants with metastatic castration-resistant prostate cancer (mCRPC).
Detailed description
This is a Phase II, international, open-label, two-arm, non-randomised study of AZD4635 in participants with mCRPC. Participants in each arm will be stratified by the presence of measurable soft tissue metastasis (per Response Evaluation Criteria in Solid Tumours [RECIST v1.1]) or bone-only metastasis (per Prostate Cancer Working Group 3 [PCWG3 criteria]). There will be no formal comparisons between treatment arms.
AZD4635 plus durvalumab (Arm A) will consist of 80 participants with mCRPC previously treated with one or more approved new hormonal agent(s) (NHAs) and one or more taxanes or participants who are taxane ineligible.
AZD4635 plus durvalumab plus cabazitaxel (Arm B) will consist of 80 participants mCRPC previously treated with docetaxel and one prior NHA.
As of November 2020, the Sponsor stopped enrolment in Arm A following decisions at the program level, not related to any safety issues. Ongoing participants in Arm A may continue treatment as planned.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A: AZD4635 + durvalumab | Experimental | Drug: AZD4635, Drug: DurvalumabAZD4635 plus durvalumab (Arm A) will consist of participants with mCRPC previously treated with one or more approved NHAs (eg, abiraterone acetate, enzalutamide, apalutamide and/or darolutamide), and one or more taxanes, or participants who are taxane ineligible. |
| Arm B: AZD4635 + durvalumab + cabazitaxel | Experimental | Drug: AZD4635, Drug: Durvalumab, Drug: CabazitaxelAZD4635 plus durvalumab plus cabazitaxel (Arm B) will consist of participants with mCRPC previously treated with docetaxel and one prior NHA (either abiraterone acetate or enzalutamide but not both (prior apalutamide is not allowed in Arm B). |
Who may qualify
- Ages
- 18 to 150 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- Histologically confirmed adenocarcinoma of the prostate.
- Known castrate-resistant disease.
- Evidence of disease progression ≤6 months.
- Body weight >30 kg at screening.
- Willingness to adhere to the study treatment-specific contraception requirements.
Key exclusion criteria (8 listed)
- Active brain metastases or leptomeningeal metastases.
- There must be no requirement for immunosuppressive doses of systemic corticosteroids for at least 2 weeks prior to study enrollment.
- History of pneumonitis requiring corticosteroids, second malignancy that is progressing and/or received active treatment ≤3 years before the first dose of study intervention, and hypersensitivity to polysorbate-80 if allocated to cabazitaxel.
- As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases.
- Creatinine clearance <40 mL/min (calculated by Cockcroft-Gault equation).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZD4635Subjects will receive AZD4635 orally daily | Drug | Arm A: AZD4635 + durvalumab, Arm B: AZD4635 + durvalumab + cabazitaxel |
| DurvalumabSubjects will receive intravenous durvalumab every 4 weeks for Arm A and every 3 weeks for Arm B. | Drug | Arm A: AZD4635 + durvalumab, Arm B: AZD4635 + durvalumab + cabazitaxel |
| CabazitaxelSubjects will receive intravenous cabazitaxel every 3 weeks | Drug | Arm B: AZD4635 + durvalumab + cabazitaxel |
Primary outcome
Radiographic Progression Free Survival (rPFS) in Each Arm Separately to Determine the Efficacy of AZD4635 Plus Durvalumab and of AZD4635 Plus Durvalumab Plus Cabazitaxel in Patients With Metastatic Castrate-resistant Prostate Cancer (mCRPC)
Time frame: From first dose to first documented progression or death from any cause (whichever comes first) (approximately 1 year)
rPFS was defined as the time from first dose to radiographic progression, assessed by the Investigator per RECIST 1.1 (soft tissue) and PCWG3 (Prostate Cancer Working Group 3) criteria [bone] or death from any cause, whichever occurred first.
16 secondary outcomes
rPFS by Adenosine (ADO) Signalling Gene Expression in High and Low Subgroups to Determine the Efficacy of AZD4635 Plus Durvalumab Plus Cabazitaxel in Participants With mCRPC
Time frame: From first dose to first documented progression or death from any cause (whichever comes first), up to two years
Overall Survival (OS) in Each Arm Separately to Determine the Efficacy of AZD4635 Plus Durvalumab and of AZD4635 Plus Durvalumab Plus Cabazitaxel in Participants With mCRPC
Time frame: Arm A and B: Every 90 days from the last dose of study drug up to 2 years
Number of Participants With Objective Response in Subjects With MCRPC Who Received AZD4635 Plus Durvalumab Plus Cabazitaxel
Time frame: From first dose to first documented progression or death from any cause (whichever comes first), up to two years
Number of Participants With Prostate-specifin Antigen (PSA50) Response in Subjects With MCRPC Who Received AZD4635 Plus Durvalumab Plus Cabazitaxel
Time frame: Arm A: Screening, Day 1 of each cycle up to 11 months (Each cycle was 28 days in length); Arm B: Screening, Day 1 of each cycle up to 11 months (Cycle 1 to Cycle 10 = 21 days, Cycle 11 onwards = 28 days)
Change From Baseline in Worst Pain in the Daily Activities Scales of the Brief Pain Inventory - Short Form (BPI-SF)
Time frame: Arm A: Screening, Day 1 of each cycle up to 9 months (Each cycle was 28 days in length); Arm B: Screening, Day 1 of each cycle up to 9 months (Each cycle was 21 days in length)
Change From Baseline in Average Pain in the Daily Activities Scales of the Brief Pain Inventory - Short Form (BPI-SF)
Time frame: Arm A: Screening, Day 1 of each cycle up to 9 months (Each cycle was 28 days in length); Arm B: Screening, Day 1 of each cycle up to 9 months (Each cycle was 21 days in length)
Change From Baseline in Pain Interference in the Daily Activities Scales of the Brief Pain Inventory - Short Form (BPI-SF)
Time frame: Arm A: Screening, Day 1 of each cycle up to 9 months (Each cycle was 28 days in length); Arm B: Screening, Day 1 of each cycle up to 9 months (Each cycle was 21 days in length)
Number of Participants Who Progressed Based on BPI-SF Item 3
Time frame: Arm A: Screening, Day 1 of each cycle up to 12 months (Each cycle was 28 days in length); Arm B: Screening, Day 1 of each cycle up to 12 months (Cycle 1 to Cycle 10 = 21 days, Cycle 11 onwards = 28 days)
Change From Baseline in the FACT Advanced Prostate Symptom Indext-6 (FAPSI-6), as Derived From 6 Items, the FAPSI-8 From 8 Items Within the FACT-P and the Prostate Cancer Symptoms (PCS), From the 12 Items in the Prostrate-specific Module of the FACT-P
Time frame: Arm A: Screening, Day 1 of each cycle up to 9 months (Each cycle was 28 days in length); Arm B: Screening, Day 1 of each cycle up to 9 months (Each cycle was 21 days in length)
Maximum Observed Plasma Concentration (Cmax)
Time frame: Arm A:Cycle 1 to 3, and Cycle 4 onwards, and 90-day follow-up (FU) visit up to 14 months [Each cycle was 28 days in length];Arm B: Cycle 1 to 7 and Cycle 11 onwards, and 90-day FU up to 14 months (Cycle 1 to Cycle 10 = 21 days, Cycle 11 onwards = 28 days)
Terminal Half-life (t1/2λz)
Time frame: Arm A:Cycle 1 to 3, and Cycle 4 onwards, and 90-day follow-up (FU) visit up to 14 months [Each cycle was 28 days in length];Arm B: Cycle 1 to 7 and Cycle 11 onwards, and 90-day FU up to 14 months (Cycle 1 to Cycle 10 = 21 days, Cycle 11 onwards = 28 days)
Area Under the Plasma Concentration Time Curve From Zero to the Time of the Last Measurable Concentration (AUClast)
Time frame: Arm A:Cycle 1 to 3, and Cycle 4 onwards, and 90-day follow-up (FU) visit up to 14 months [Each cycle was 28 days in length];Arm B: Cycle 1 to 7 and Cycle 11 onwards, and 90-day FU up to 14 months (Cycle 1 to Cycle 10 = 21 days, Cycle 11 onwards = 28 days)
Area Under the Plasma Concentration Time Curve From Zero to 24 Hours [AUC(0-24)]
Time frame: Arm A:Cycle 1 to 3, and Cycle 4 onwards, and 90-day follow-up (FU) visit up to 14 months [Each cycle was 28 days in length];Arm B: Cycle 1 to 7 and Cycle 11 onwards, and 90-day FU up to 14 months (Cycle 1 to Cycle 10 = 21 days, Cycle 11 onwards = 28 days)
Area Under the Plasma Concentration Time Curve From Zero Extrapolated to Infinity (AUCinf)
Time frame: Arm A:Cycle 1 to 3, and Cycle 4 onwards, and 90-day follow-up (FU) visit up to 14 months [Each cycle was 28 days in length];Arm B: Cycle 1 to 7 and Cycle 11 onwards, and 90-day FU up to 14 months (Cycle 1 to Cycle 10 = 21 days, Cycle 11 onwards = 28 days)
Apparent Volume of Distribution During the Terminal Phase (Vz/F)
Time frame: Arm A:Cycle 1 to 3, and Cycle 4 onwards, and 90-day follow-up (FU) visit up to 14 months [Each cycle was 28 days in length];Arm B: Cycle 1 to 7 and Cycle 11 onwards, and 90-day FU up to 14 months (Cycle 1 to Cycle 10 = 21 days, Cycle 11 onwards = 28 days)
Number of Subjects With Serious and Non-serious Adverse Events
Time frame: Arm A: From Screening up to 14 months (Each cycle was 28 days in length); Arm B: From Screening up to 14 months (Cycle 1 to Cycle 10 was 21 days in length, and Cycle 11 onwards was 28 days in length)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Related InfoLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christopher J Sweeney, MBBS principal investigator
Dana-Farber Cancer Institute
16 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AZD4635, Durvalumab and Cabazitaxel in people with Progressive Metastatic Castrate-Resistant Prostate Cancer, run by AstraZeneca at 16 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 27 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United States, Spain, South Korea, Belgium, France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Radiographic Progression Free Survival (rPFS) in Each Arm Separately to Determine the Efficacy of AZD4635 Plus Durvalumab and of AZD4635 Plus Durvalumab Plus Cabazitaxel in Patients With Metastatic Castrate-resistant Prostate Cancer (mCRPC) (time frame: From first dose to first documented progression or death from any cause (whichever comes first) (approximately 1 year)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Aug 2023.