Condition category
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting

Contact information



Primary contact

Dr Study Coordinator


Contact details

Clinical Trials Unit
MP 131
Tremona Road
SO16 6YD
United Kingdom

Additional identifiers

EudraCT number

2013-002391-41 number

Protocol/serial number


Study information

Scientific title



Study hypothesis

Docetaxel and prednisolone chemotherapy (DP) is the only treatment proven to extend survival as first line chemotherapy in metastatic castration resistant prostate cancer (mCRPC). Clinical benefit from DP is modest however and DP resistance is a common problem raising a pressing clinical need to build on the benefits of DP.
One approach to this is to develop a rational combination of docetaxel with a drug with likely clinical synergy and complimentary toxicity profile that might circumvent DP resistance. AKT (Protein Kinase B) activation is common in prostate cancer reaching up to 100% in metastatic disease. This contributes to disease progression and DP resistance. AZD5363 is an orally available potent AKT inhibitor. The ProCAID trial will test the hypothesis that AZD5363 prolongs progression free survival when combined with DP for mCRPC.

More details can be found at:

Ethics approval

13/LO/1691; First MREC approval date 13/11/2013

Study design

Interventional open label phase I/randomised, double-blind phase II; Design type: Treatment

Primary study design


Secondary study design

Randomised controlled trial

Trial setting


Trial type


Patient information sheet


Topic: National Cancer Research Network; Subtopic: Prostate Cancer; Disease: Prostate


IMP, AZD5363

Intervention type



Phase I/II

Drug names


Primary outcome measures

Determination of a suitable dose of AZD5363; Timepoint(s): Phase I

Secondary outcome measures

1. AZD5363 pharmacokinetics in combination with DP; Timepoint(s): Phase I
2. Biochemical (PSA) response rates according to PCWG2 criteria; Timepoint(s): Phase II
3. Bone pain changes using the BPI Questionnaire; Timepoint(s): Phase II
4. Overall survival; Timepoint(s): Phase II
5. PFS excluding biochemical (PSA) alone progression; Timepoint(s): Phase II
6. Progression Free Survival from start of study treatment; Timepoint(s): Phase II - Primary outcome
7. Safety and tolerability profiles; Timepoint(s): Phase I and II

Overall trial start date


Overall trial end date


Reason abandoned


Participant inclusion criteria

1.Histologically or cytologically proven mCRPC with documented metastases (measurable or evaluable disease is acceptable) now eligible for treatment with docetaxel chemotherapy
2.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¿26:11481159):
2.1. 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.
2.2. Radiographic progression of nodal or visceral metastases as defined by RECIST version 1.1 (Eur J Cancer 2009¿45:228). See Appendix 5
2.3. The appearance of two or more new bony metastases
3.Serum testosterone <1.7 nmol/L (ongoing LHRH analogue or antagonist therapy is permitted to maintain a castrate state)
4.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)
5.No antiandrogen withdrawal response. Withdrawal responses typically occur following combined androgen blockade (LHRH analogue/antagonist or orchidectomy combined with an antiandrogen)
as initial therapy for a prolonged period, or in patients who respond to an antiandrogen as secondline therapy. Consistent with PCWG2
guidelines, investigators should evaluate such patients for withdrawal response for 6 weeks and then confirm disease progression. Investigators need not wait to assess withdrawal response in patients who did not respond, or who showed a PSA decline for ≤ 3 months, after an antiandrogen was administered as a secondline or later intervention
6.ECOG performance status 0 or 1
7.Hb ≥ 9g/dL¿ platelets ≥ 100 x 109/L¿ neutrophils ≥ 1.5 x109/L
8.Bilirubin ≤ ULN ¿ ALT and AST ≤ 1.5 x ULN.
9.Sodium and potassium within the normal range for the site
10.Able to swallow study drugs (without crushing/opening in the case of AZD5363)
11.Life expectancy > 3 months
12.Aged 18 years or over
13.Provision of written informed consent

Participant type


Age group




Target number of participants

Planned Sample Size: 150; UK Sample Size: 150; Description: England: Phase 1 – up to 12, Phase II - 105
N. Ireland: Phase II - 9
Scotland: Phase 1 – up to 6, Phase II - 9
Wales: Phase II - 9

Participant exclusion criteria

1.Previous treatment with cytotoxic chemotherapy (patients may have received previous or ongoing bisphosphonates or denosumab). There are no restrictions on prior use of second generation hormonal therapies e.g. abiraterone, enzalutamide
2.Prior malignancy with an estimated ≥ 30% chance of relapse within 2 years following curative treatment
3.Previously identified brain metastases, or spinal cord compression unless treated with full functional recovery
4.Prior radiotherapy to > 30% of bone marrow
5.Administration of an investigational agent within 30 days of first dose of study medication
6.Type I or II diabetes mellitus requiring either insulin or oral hypoglycaemics for routine management. Patients with type II diabetes mellitus that is well controlled by dietary measures alone are eligible to participate. Patients found to have a fasting glucose ≥7 mmol/L (≥126 mg/dL) or glycosylated haemoglobin >8% (64 mmol/mol) at screening should be assessed for appropriate management according to local policy. Those in whom dietary measures alone provide good diabetic control will be eligible for inclusion
7.Malabsorption syndrome, previous gastrointestinal surgery, or other gastrointestinal condition that may affect drug absorption
8.Coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, angina pectoris or congestive heart
failure (NYHA ≥ grade 2) within the last 6 months
9.Abnormal echocardiogram (LVEF 10.Uncontrolled hypotension (systolic blood pressure <90 mmHg and/or diastolic blood pressure <50 mmHg)
11.QTc interval of >480 msec at two or more time points within a 24 hour period
12.Proteinuria (3+ on dipstick analysis or >500 mg/24 hours) or creatinine >1.5 x ULN concurrent with creatinine clearance <50 mL/min
13.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)
14.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)
15.Unresolved toxicity ≥ grade 2 (except alopecia) from previous cancer therapy
16.Patients with a partner of childbearing 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
17.Known hypersensitivity to AZD5363, its excipients, or drugs in its class
18.Previous exposure to agents with the following mechanisms of action:
18.1. 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)
18.2. any compound with mixed PI3K and mammalian target of rapamycin (mTOR) kinase pharmacology (e.g., BEZ235,
GDC0980, PF04691502, PF05212384, GSK2126458, XL765)
18.3. 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).

Recruitment start date


Recruitment end date



Countries of recruitment

United Kingdom

Trial participating centre

Clinical Trials Unit, MP 131, Tremona Road
SO16 6YD
United Kingdom

Sponsor information


Southampton University Hospitals NHS Trust (UK)

Sponsor details

Tremona Road
SO16 6YD
United Kingdom

Sponsor type

Hospital/treatment centre



Funder type


Funder name

Cancer Research UK (UK)

Alternative name(s)


Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit


United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes