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Prostate CancerPhase 1/2ProCAIDNCT02121639

Open Label Phase I/Randomised,Double Blind Phase II Study in mCRPC of AZD5363 In Combination With DP Chemotherapy

A Phase 1/2 study testing AZD5363 in people with Prostate Cancer, run by University Hospital Southampton NHS Foundation Trust at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The aim of the ProCAID study is to determine if the addition of the AKT inhibitor AZD5363 to docetaxel and prednisolone (DP) prolongs progression free survival (PFS) in Metastatic castration resistant prostate cancer to a degree worthy of further investigation Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Prostate Cancer
What is being tested?
AZD5363
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
160 participants
Where
1 siteUnited Kingdom
Study dates
29 Jan 2014to 13 Sep 2021
Phase
Phase 1/2
Are there results?
None posted in the registry

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 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically or cytologically proven mCRPC with documented metastases (measurable or evaluable disease is acceptable) now eligible for treatment with docetaxel chemotherapy
  • Disease progression since the last change in therapy defined by one or more of the following according to the Prostate Cancer Working Group (PCWG2) criteria (J Clin Oncol 2008;26:1148-1159):
  • PSA progression as defined by the prostate cancer working group (2) (PCWG2) criteria (Scher et al. 2008 J Clin Oncol. 26; 1148). This must be based on a series of at least 3 readings at least 7 days apart. The 3rd reading must be >= 2ng/ml. In the event where an intermediate reading is lower than a previous reading, then the patient will still be eligible (ie. the 3 readings do not need to be consecutive). The first of the three readings must have been obtained after commencing the previous systemic therapy, or, in the case of androgen receptor antagonists, after discontinuing.
  • Radiographic progression of nodal or visceral metastases as defined by RECIST version 1.1 (Eur J Cancer 2009;45:228). See Appendix 5 iii. The appearance of two or more new bony metastases
  • Serum testosterone <1.7 nmol/L (ongoing LHRH analogue or antagonist therapy is permitted to maintain a castrate state)
  • Discontinuation of prior therapies for prostate cancer ≥ 4 weeks prior to commencing study treatment (with the exception of an LHRH agonist or antagonist where required for ongoing testosterone suppression)
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  • No current anti-androgen withdrawal response from bicalutamide or flutamide. Consistent with PCWG2 guidelines, investigators should evaluate patients to exclude withdrawal response for 6 weeks after stopping bicalutamide or flutamide. Investigators need not wait to assess for withdrawal response in patients who did not respond, or who showed a PSA decline for ≤ 3 months, after bicalutamide or flutamide was administered as a second-line or later intervention.
  • ECOG performance status 0 or 1
  • Hb ≥ 9g/dL; platelets ≥ 100 x 109/L; neutrophils ≥ 1.5 x109/L
  • Bilirubin ≤ ULN ; ALT and AST ≤ 1.5 x ULN
  • Sodium and potassium within the normal range for the site
  • Able to swallow study drugs (without crushing/opening in the case of AZD5363)
  • Life expectancy > 3 months
  • Aged 18 years or over
  • Provision of written informed consent

Who cannot join

  • Previous treatment with cytotoxic chemotherapy for castrate resistant prostate cancer. Patients may have received previous docetaxel for up to 6 cycles given in the 'hormone sensitive setting' or ongoing bisphosphonates or denosumab. There are no restrictions on prior use of second generation hormonal therapies e.g. abiraterone, enzalutamide as long as they have been discontinued ≥ 2 weeks prior to commencing study treatment.
  • Prior malignancy with an estimated ≥ 30% chance of relapse within 2 years following curative treatment
  • Previously identified brain metastases, or spinal cord compression unless treated with full functional recovery
  • Prior radiotherapy to > 30% of bone marrow
  • Administration of an investigational agent within 30 days of first dose of study medication
  • Patients will be excluded with any of:
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  • Diabetes mellitus type I ii. Fasting plasma glucose [fasting is defined as no calorific intake for at least 8 hours] of either ≥ 7.0mmol/L (126 mg/dL) for those patients without a pre-existing diagnosis of Type 2 diabetes mellitus or ≥ 9.3 mmol/L (167mg/dL) for those patients with a pre-existing diagnosis of Type 2 diabetes mellitus iii. Glycosylated haemoglobin (HbA1C) ≥8.0% (63.9 mmol/mol) iv. Requirement for insulin for routine diabetic management and control v. Requirement for more than two oral hypoglycaemic medications for routine diabetic management and control.
  • Malabsorption syndrome, previous gastrointestinal surgery, or other gastrointestinal condition that may affect drug absorption
  • Coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, angina pectoris or congestive heart failure (NYHA ≥ grade 2) within the last 6 months
  • Abnormal echocardiogram or MUGA (LVEF should be normal according to the criteria used within the treating institution
  • Uncontrolled hypotension (systolic blood pressure <90 mmHg and/or diastolic blood pressure <50 mmHg)
  • QTc interval of >480 msec at two or more time points within a 24 hour period
  • Proteinuria (either 3+ on dipstick analysis or >500 mg/24 hours) or creatinine >1.5 x ULN concurrent with creatinine clearance <50 mL/min (assessed as per local practice e.g. by Cockcroft and Gault estimation)
  • Exposure to potent inhibitors or inducers of CYP3A4 or CYP2D6 or substrates of CYP3A4 within 2 weeks before the first dose of study treatment (3 weeks for St John's Wort)
  • Unresolved toxicity ≥ grade 2 (except alopecia) from previous cancer therapy
  • Patients with a partner of child-bearing potential who are not using a highly effective method of contraception, who are unwilling to use condoms during the study and for 30 days after the last dose of study drug
  • Known hypersensitivity to AZD5363, its excipients, or drugs in its class
  • Previous exposure to agents with the following mechanisms of action:
  • inhibition of AKT (e.g., MK2206, GDC0068, GSK2110183, GSK2141795)any inhibitor with PI3K pharmacology (e.g., GDC0941, XL147, BKM120, PX866, BYL719, AMG319, GDC0032, INK1117, INK119)
  • any compound with mixed PI3K and mammalian target of rapamycin (mTOR) kinase pharmacology (e.g., BEZ235, GDC0980, PF04691502, PF05212384, GSK2126458, XL765)
  • or any mTOR kinase inhibitor (e.g., AZD8055, AZD2014, OSI027, INK128) Note: Do not exclude patients previously treated with a rapalogue (allosteric inhibitor of mTOR; mTORC1 complex inhibitor) - including temisirolimus (Torisel; Pfizer), everolimus (Affinitor; Novartis), ridoforolimus (Ariad).

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

  • Southampton General Hospital

    Southampton, Hampshire, SO16 6YD

Other trials in United Kingdom

About this study

Official title: An Open Label Phase I/Randomised, Double Blind Phase II Study in Metastatic Castration Resistant Prostate Cancer of AZD5363 In Combination With Docetaxel and Prednisolone Chemotherapy (ProCAID)

The aim of the ProCAID study is to determine if the addition of the AKT inhibitor AZD5363 to docetaxel and prednisolone (DP) prolongs progression free survival (PFS) in Metastatic castration resistant prostate cancer to a degree worthy of further investigation

Conditions
Prostate Cancer
Being tested
Placebo, AZD5363
Keywords
Metastatic Castration Resistant Prostate Cancer, AZD5363, Docetaxel, Prednisolone
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PlaceboDrug

  • AZD5363Drug

Study groups in NCT02121639
Study groupRoleWhat they receive
AZD5363ExperimentalAZD5363
Receives: Drug: AZD5363
PlaceboPlacebo comparatorPlacebo
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase I:Determination of a suitable dose of AZD5363

    Phase I:Determination of a suitable dose of AZD5363 using a 4 days on/3 days off continuous schedule, in combination with Docetaxol and prednisolone chemotherapy

    Measured: Up to 18 months

  2. Phase II: Progression free survival

    Phase II: Progression free survival (PFS) in patients receiving AZD5363 versus placebo when combined with Docetaxol and prednisolone chemotherapy (DP) in metastic castration resistant prostate cancer (mCRPC)

    Measured: 5 years

Secondary outcomes (6)

  1. Phase I: Safety and tolerability profiles

    Phase I: Safety and tolerability profiles using Common Terminology Criteria for Adverse Events (CTCAE) version 4.03

    Measured: Up to 18 months

  2. Phase I: AZD5363 pharmacokinetics Area Under Curve (AUC) Time Frame: predose, 2, 4, 8, 24,144 hours post-dose

    Phase I: AZD5363 pharmacokinetics in combination with Docetaxol and prednisolone chemotherapy

    Measured: Up to 18 months

  3. Phase II: Bone Pain

    Phase II: Bone pain changes using the brief pain inventory

    Measured: 5 years

  4. Phase II: Progression Free Survival

    Phase II: Progression Free Survival excluding biochemical (Prostate Specific Antigen - PSA) alone progression

    Measured: 5 years

  5. Phase II: Biochemical (PSA) response rates according to PCWG2 criteria

    Phase II: Biochemical (Prostate Specific Antigen - PSA) response rates according to Prostate Cancer Working Gourp (PCWG2) criteria

    Measured: 5 years

  6. Phase II: Safety and tolerability profiles using CTCAE version 4.03

    Phase II: Safety and tolerability profiles using Common Terminology Criteria for Adverse Events (CTCAE) version 4.03

    Measured: 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Apr 2014 (estimated)
  2. Study start29 Jan 2014
  3. Primary completion8 Oct 2020
  4. Study completion13 Sep 2021

Resources

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 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
160 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02121639
Sponsor's protocol ID
RHMCAN0935
Acronym
ProCAID
Status last verified
May 2022
First submitted
16 Apr 2014
Last updated
5 May 2022
Results posted
No
Data monitoring committee
Yes

Publications

  • Crabb SJ, Griffiths G, Marwood E, Dunkley D, Downs N, Martin K, Light M, Northey J, Wilding S, Whitehead A, Shaw E, Birtle AJ, Bahl A, Elliott T, Westbury C, Sundar S, Robinson A, Jagdev S, Kumar S, Rooney C, Salinas-Souza C, Stephens C, Khoo V, Jones RJ. Pan-AKT Inhibitor Capivasertib With Docetaxel and Prednisolone in Metastatic Castration-Resistant Prostate Cancer: A Randomized, Placebo-Controlled Phase II Trial (ProCAID). J Clin Oncol. 2021 Jan 20;39(3):190-201. doi: 10.1200/JCO.20.01576. Epub 2020 Dec 16.

    PubMed 33326257

  • Crabb SJ, Birtle AJ, Martin K, Downs N, Ratcliffe I, Maishman T, Ellis M, Griffiths G, Thompson S, Ksiazek L, Khoo V, Jones RJ. ProCAID: a phase I clinical trial to combine the AKT inhibitor AZD5363 with docetaxel and prednisolone chemotherapy for metastatic castration resistant prostate cancer. Invest New Drugs. 2017 Oct;35(5):599-607. doi: 10.1007/s10637-017-0433-4. Epub 2017 Feb 1.

    PubMed 28144789

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing AZD5363 in people with Prostate Cancer, run by University Hospital Southampton NHS Foundation Trust at 1 site in United Kingdom.

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 15 inclusion and 21 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 5 May 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Phase I:Determination of a suitable dose of AZD5363 (time frame: Up to 18 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02121639, which also lists 2 linked publications.

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 5 May 2022.

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