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Prostate CancerPhase 2NCT03385655

Prostate Cancer Biomarker Enrichment and Treatment Selection

A Phase 2 study testing Adavosertib, Savolitinib and Darolutamide in people with Prostate Cancer, run by Canadian Cancer Trials Group at 11 sites in Canada.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

The purpose of the pre-study screening is to test for DNA abnormalities or biomarkers. 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?
Adavosertib, Savolitinib and Darolutamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
200 participants
Where
11 sitesCanada
Study dates
1 Aug 2018to 31 Dec 2025
Phase
Phase 2
Are there results?
Not yet: the study is under way

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

  • The following will be required prior to REGISTRATION:
  • Patients must have histologically confirmed adenocarcinoma of the prostate without pathologic or clinical evidence (e.g. PSA < 2.0 μg/L with liver metastases) of small cell neuroendocrine differentiation.
  • Patients must consent prior to blood collection for screening correlative testing by a central reference laboratory. The screening blood sample cannot be sent for analysis prior to screening registration.
  • All patients must have consented to the release of a tumour block from their primary or metastatic tumour. The centre/pathologist must have agreed to the submission of the specimen(s). Contact CCTG if no archival tissue is available.
  • Patients must have evidence of castrate resistance with either biochemical or radiological disease progression in the setting of surgical or medical castration:
  • PSA Progression:
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  • Minimum of two rising PSA values from a baseline measurement with an interval of ≥ 1 week between each measurement
  • PSA must be ≥ 2.0 µg/L (ng/mL)
  • Objective progression:
  • RECIST 1.1, or
  • PCWG3 Criteria for bone progression
  • Surgical/Medical Castration:
  • Prior bilateral orchiectomy, or
  • LHRH agonist/antagonist and testosterone < 50 ng/dL or < 1.7 nmol/L. LHRH agonist/antagonist therapy must be maintained for the duration of study therapy and if previously discontinued, must be restarted and castrate level of testosterone present.
  • Patients must be ≥18 years of age.
  • ECOG performance status 0 or 1 (Appendix I) and have a life expectancy of ≥ 6 months.
  • Patients must have radiologically documented disease (measurable or non-measurable as defined by RECIST 1.1. Patients with elevated PSA only are not eligible.
  • Neutrophils ≥ 1.5 x 10^9/L
  • Platelets ≥ 100 x 10^9/L
  • Hemoglobin ≥ 90 g/L; contact CCTG if hemoglobin is between 80-89 g/L, patient is not decompensated, is asymptomatic and transfusion is not indicated.
  • Serum potassium within normal limits
  • Bilirubin ≤ 1.5 ULN; if confirmed Gilbert's then bilirubin ≤ 3.0 x ULN
  • ALT ≤ 2.5 x ULN; if patient has liver metastases ≤ 5.0 x ULN
  • Serum creatinine ≤ 1.5 x ULN or Creatinine clearance ≥ 45 mL/min; measured directly by 24-hour urine sampling OR as calculated by Cockcroft and Gault equation: Males: GFR = 1.23 x (140-age) x weight in kg/serum creatinine in μmol/L
  • Patient consent for screening and subsequent enrollment (as applicable) must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to screening and subsequent enrollment (as applicable) in the trial to document their willingness to participate.
  • Additional Criteria to be met prior to SUB-STUDY ENROLLMENT:
  • Patients must have recovered from any treatment-related toxicities prior to enrollment (unless ≤ grade 1, irreversible, or considered by investigator as not clinically significant).
  • Prior major surgery is permitted provided that a minimum of 14 days have elapsed between any major surgery and enrollment (7 days for minor surgery e.g. port insertion), and that wound healing has occurred.
  • Prior external beam radiation or radium-223 is permitted provided a minimum of 28 days (4 weeks) have elapsed between the last dose and enrollment. Consult CCTG if patients have received other therapeutic radioisotopes. Exceptions may be made for low-dose non-myelosuppressive radiotherapy after consultation with CCTG. Concurrent radiation is not permitted. If radiation is required for example for pain control, it must be completed prior to enrollment. Prior strontium-89 at any time is not permitted.
  • Previous Hormone Therapy: Patients must have received prior hormonal treatment with at least one of: abiraterone acetate, enzalutamide, apalutamide (ARN-509), darolutamide (ODM-201), TAK-700 and TOK-001 or other next-generation AR-pathway inhibitor (if agent is not listed, must be discussed and approved with CCTG prior to registration). Consult substudies for additional criteria
  • Prior cytotoxic therapy: Patients may have received cytotoxic therapy in the castrate sensitive setting as well as up to 1 regimen of cytotoxic therapy in the CRPC setting
  • Patients must have an adequate washout prior to enrollment as follows:
  • Longest of one of the following:
  • Standard cycle length of standard therapies;
  • Two weeks;
  • The longer of 30 days or 5 half-lives for investigational agents;
  • Patients must have discontinued anti-androgens for at least 4 weeks prior to substudy entry/enrollment (at least 6 weeks for bicalutamide).
  • LHRH agonist therapy must continue unless surgically castrated. Note: after discussion, CCTG selected patients may be screened prior to adequate washout.
  • Patient must have progressed (biochemically or radiologically, as defined in 4.1.4) during or after their last systemic therapy
  • Patients must be accessible for treatment and follow up. Patients registered enrolled on this trial must be treated and followed at the participating centre. This implies there must be reasonable geographical limits (for example: 1 ½ hour's driving distance) placed on patients being considered for this trial.
  • Investigators must assure themselves the patients enrolled on this trial will be available for complete documentation of the treatment, adverse events, response assessment and follow-up.
  • Patients must agree to return to their primary care facility for any adverse events, which may occur through the course of the trial.
  • In accordance with CCTG policy, protocol treatment is to begin within 2 working days of patient enrollment.
  • Men of childbearing potential must have agreed to use a highly effective contraceptive method during study drug treatment for 6 months after stopping treatment and should not father a child or donate sperm during this period.
  • In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation, or vasectomy / vasectomized partner. However, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he is responsible for beginning contraceptive measures.

Who cannot join

  • Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer, or other solid tumours curatively treated with no evidence of disease for ≥ 2 years.
  • Patients with central nervous system (CNS) involvement unless at least 4 weeks from prior therapy completion (including radiation and/or surgery) AND clinically stable and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastases. Patients with epilepsy not due to CNS metastases are eligible as long as no contraindication or concern with drug interactions.
  • Patients with serious illnesses or medical conditions which could cause unacceptable safety risks or would not permit the patient to be managed according to the protocol. This includes but is not limited to:
  • active infection requiring systemic therapy;
  • active or known human immunodeficiency virus (HIV) with detectable viral load;
  • uncontrolled or recent clinically significant cardiac disease, including:
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  • angina pectoris, symptomatic pericarditis, coronary artery bypass grafting, coronary angioplasty, or stenting, or myocardial infarction in the previous 12 months;
  • history of documented congestive heart failure (New York Heart Association functional classification III-IV) or cardiomyopathy;
  • history of any cardiac arrhythmias, e.g. ventricular, supraventricular, nodal arrhythmias, or conduction abnormality in the previous 12 months;
  • patients with uncontrolled hypertension.
  • Patients with significant liver diseases including viral/other hepatitis, current alcohol abuse or cirrhosis.
  • Patients who are unable to swallow oral medication and/or have impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g. Crohn's disease, ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, active bowel inflammation (e.g. diverticulitis) or small bowel resection), unless agreed with CCTG (exceptions may be given if parenteral substudy is available/appropriate.
  • Patients who require continued or concurrent treatment with:
  • Systemic corticosteroids at a dose equivalent to prednisone > 10 mg daily. Topical applications (e.g. rash), inhaled sprays (e.g. obstructive airways diseases), eye drops or local injections (e.g. intra-articular) are allowed.
  • Bisphosphonates / denosumab for reasons other than hypercalcemia, osteoporosis or prevention of skeletal-related events.
  • Other anti-cancer or investigational agents (except LHRH)
  • History of hypersensitivity to any of the study drugs or any excipient.
  • Patients with a history of non-compliance to medical regimens.
  • Patients who have received growth factors within 28 days prior to initiation of dosing of study drug or who are likely to require treatment with growth factors throughout the duration of the trial.

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

Canada11 sites

  • Cross Cancer Institute

    Edmonton, Alberta, T6G 1Z2

  • QEII Health Sciences Centre

    Halifax, Nova Scotia, B3H 1V7

  • Juravinski Cancer Centre at Hamilton Health Sciences

    Hamilton, Ontario, L8V 5C2

  • London Regional Cancer Program

    London, Ontario, N6A 5W9

  • CHUM-Centre Hospitalier de l'Universite de Montreal

    Montreal, Quebec, H2X 3E4

  • The Jewish General Hospital

    Montreal, Quebec, H3T 1E2

  • Ottawa Hospital Research Institute

    Ottawa, Ontario, K1H 8L6

  • Allan Blair Cancer Centre

    Regina, Saskatchewan, S4T 7T1

  • Saskatoon Cancer Centre

    Saskatoon, Saskatchewan, S7N 4H4

  • University Health Network

    Toronto, Ontario, M5G 2M9

  • BCCA - Vancouver Cancer Centre

    Vancouver, British Columbia, V5Z 4E6

Other trials in Canada

About this study

Official title: Prostate Cancer Biomarker Enrichment and Treatment Selection (PC-BETS) Study

The purpose of the pre-study screening is to test for DNA abnormalities or biomarkers.

Read the detailed description

This testing will be done on a samples of blood to see whether or not patients are eligible to take part in one of the sub-studies. Each study will be looking at what effects a new drug or drugs has on prostate cancer and will also be looking at the side effects of treatment. The purpose of the main studies is to see if the biomarkers that were identified screening samples can help predict which patients are most likely to be helped by that drug or drugs and to see how the cancer cells respond to treatment.

Conditions
Prostate Cancer
Being tested
Adavosertib, Savolitinib, Darolutamide, CFI-400945, Ipatasertib
Medical subject headings
Prostatic Neoplasms

What participants receive

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

  • AdavosertibDrug

    250mg, may dose escalate to 300mg if no drug-related GI tox in cycle 1

  • SavolitinibDrug

    600mg once daily, orally.

  • DarolutamideDrug

    600mg twice daily, orally.

  • CFI-400945Drug

    Dose level assigned at enrollment, starting at 32mg/day on Days 1-7 and 15-21 or 15-28 depending on toxicity experienced.

  • IpatasertibDrug

    400mg daily 3 weeks on, 1 week off

  • Durvalumab and TremelimumabDrug

    Durvalumab 1500mg day 1 every 4 weeks; Tremelimumab 225mg day 1 cycle 1

  • CarboplatinDrug

    AUC 5 IV 60min Day 1 q 21 days

Study groups in NCT03385655
Study groupRoleWhat they receive
WEE-1 inhibitor - ARM CLOSEDExperimentalNot described
Receives: Drug: Adavosertib
cMET inhibitorExperimentalNot described
Receives: Drug: Savolitinib
novel non-steroidal androgen receptor (AR) antagonistExperimentalNot described
Receives: Drug: Darolutamide
CFI400945 PLK4 inhibitor - ARM CLOSEDExperimentalNot described
Receives: Drug: CFI-400945
Ipatasertib AKT inhibitorExperimentalNot described
Receives: Drug: Ipatasertib
Durvalumab and Tremelimumab immunotherapyExperimentalNot described
Receives: Drug: Durvalumab and Tremelimumab
Carboplatin platinum based chemotherapyExperimentalNot described
Receives: Drug: Carboplatin

What is being measured

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

  1. Clinical benefit rate defined as proportion of patients who had PSA decline ≥ 50%, complete or partial objective response, or Stable disease for ≥ 12 weeks.

    Measured: 2 years

Secondary outcomes (6)

  1. Measure effect of each study drug on PSA decline

    Measured: 2 years

  2. Measure objective response as determined by RECIST 1.1 criteria

    Measured: 2 years

  3. Number and severity of adverse events

    Measured: 2 years

  4. Measure effect of each study drug on time to PSA progression

    Measured: 2 years

  5. To summarize progression-free survival

    Measured: 2 years

  6. To summarize overall survival

    Measured: 2 years

Timeline

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

  1. First posted28 Dec 2017
  2. Study start1 Aug 2018
  3. Primary completion7 Oct 2024
  4. Study completion31 Dec 2025 (estimated)

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 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
200 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03385655
Sponsor's protocol ID
I234
Status last verified
Aug 2025
First submitted
12 Dec 2017
Last updated
21 Aug 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Maia MC, Salgia M, Pal SK. Harnessing cell-free DNA: plasma circulating tumour DNA for liquid biopsy in genitourinary cancers. Nat Rev Urol. 2020 May;17(5):271-291. doi: 10.1038/s41585-020-0297-9. Epub 2020 Mar 17.

    PubMed 32203306

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Adavosertib, Savolitinib and Darolutamide in people with Prostate Cancer, run by Canadian Cancer Trials Group at 11 sites in Canada.

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 45 inclusion and 19 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: under way, not looking for participants, as of the sponsor's last update on 21 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in Canada. 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?

This study is still under way. Results are not available in the source record yet.

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?

Clinical benefit rate defined as proportion of patients who had PSA decline ≥ 50%, complete or partial objective response, or Stable disease for ≥ 12 weeks. (time frame: 2 years). 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 NCT03385655, which also lists 1 linked publication.

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 21 Aug 2025.

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