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

NCT02121639 | Completed Phase 1 DMC

• 1 other identifier: RHMCAN0935
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Prostate Cancer

Keywords

Metastatic Castration Resistant Prostate Cancer; AZD5363; Docetaxel; Prednisolone

Outcome Measures

Primary Outcomes (2)

• 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

  Up to 18 months

• 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)

  5 years

Secondary Outcomes (6)

• Phase I: Safety and tolerability profiles

  Up to 18 months

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

  Up to 18 months

• Phase II: Bone Pain

  5 years

• Phase II: Progression Free Survival

  5 years

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

  5 years

Study Arms (2)

AZD5363

EXPERIMENTAL

AZD5363

Drug: AZD5363

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Placebo DRUG

Placebo

AZD5363 DRUG

AZD5363

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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):
• i. 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.
• ii. 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)
• 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

You may not qualify if:

• 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:
• i. 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

Sponsors & Collaborators

• University Hospital Southampton NHS Foundation Trust: lead
• AstraZeneca: collaborator
• Cancer Research UK: collaborator

Study Sites (1)

Southampton General Hospital

Southampton, Hampshire, SO16 6YD, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 33326257 DERIVED

• 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.

  PMID: 28144789 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

capivasertib

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2014
• First Posted: April 23, 2014
• Study Start: January 29, 2014
• Primary Completion: October 8, 2020
• Study Completion: September 13, 2021
• Last Updated: May 5, 2022

Record last verified: 2022-05

Locations

GB (1)