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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02747342




Registration number
NCT02747342
Ethics application status
Date submitted
19/04/2016
Date registered
21/04/2016
Date last updated
6/01/2020

Titles & IDs
Public title
A Phase 1 Trial of SHR3680 With or Without SHR3162 in Prostate Cancer
Scientific title
A Phase 1 Trial of SHR3680 With or Without SHR3162 in Subjects With Metastatic Castration-Resistant Prostate Cancer
Secondary ID [1] 0 0
SHR3680-002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neoplasm 0 0
Prostate Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - SHR3680; SHR3162

Experimental: SHR3680; SHR3680+SHR3162 - In dose esclation and expansion phase, SHR3680 will be administered orally In combination phase, SHR3680 will be administered together with SHR3162


Treatment: Drugs: SHR3680; SHR3162
SHR3680 will be administered orally in dose escalation/expansion phase,
SHR3680 will be administered orally at a fixed dose together with SHR3162 in combination phase.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Maximum tolerated dose (MTD) - MTD is defined as the maximum dose level at which no more than 1 out of 3 participants experience a DLT within the first 4 weeks of multiple dosing
Timepoint [1] 0 0
4 weeks
Primary outcome [2] 0 0
Recommended Phase 2 doses (RP2Ds) - RP2D will be determined based on the available data for toxicity and PK.
Timepoint [2] 0 0
24 months
Secondary outcome [1] 0 0
Number of participants with treatment-emergent adverse events - The number and proportion of subjects experiencing treatment-emergent AEs (TEAE); drug exposure; clinically significant changes in laboratory parameters, vital signs, physical examinations, weight, ECOG performance status, ECG abnormalities, number and causes of deaths.
Timepoint [1] 0 0
24 months
Secondary outcome [2] 0 0
The AUC of SHR3680 and SHR3162 (area under the curve) - The AUC of SHR3680 given as BID 240 mg tablets in combination with SHR3162
Timepoint [2] 0 0
4 weeks
Secondary outcome [3] 0 0
The cMax (peak plasma concentration) of SHR3680 and SHR3162 - The cMax (peak plasma concentration) of SHR3680 given as BID 240 mg tablets in combination with SHR3162
Timepoint [3] 0 0
4 weeks
Secondary outcome [4] 0 0
PSA reduction - Percentage of participants reaching at least a 50% reduction in prostate specific antigen (PSA) at Week 12 as compared to baseline
Timepoint [4] 0 0
12 weeks
Secondary outcome [5] 0 0
PSA progression - Time to reach the PSA Progression
Timepoint [5] 0 0
24 months
Secondary outcome [6] 0 0
Objective response rate (ORR) - the proportion of patients with tumor size reduction of a predefined amount and for a minimum time periodthe proportion of patients with tumor size reduction of a predefined amount and for a minimum time periodthe proportion of patients with tumor size reduction of a predefined amount and for a minimum time periodthe proportion of patients with tumor size reduction of a predefined amount and for a minimum time periodthe proportion of patients with tumor size reduction of a predefined amount and for a minimum time periodthe proportion of patients with tumor size reduction of a predefined amount and for a minimum time periodthe proportion of patients with tumor size reduction of a predefined amount and for a minimum time periodthe proportion of patients with tumor size reduction of a predefined amount and for a minimum time period
Timepoint [6] 0 0
24 months
Secondary outcome [7] 0 0
Radiological progression-free survival (PFS) - the length of time during and after the treatment
Timepoint [7] 0 0
24 months

Eligibility
Key inclusion criteria
Inclusion Criteria

1. Male 18 years and older

2. Ability to understand the purposes and risks of the trial and his/her signed informed
consent form approved by the HREC of the trial site, which must be obtained before
entering the trial

3. Histologically or cytologically confirmed adenocarcinoma of the prostate without
neuroendocrine differentiation or small cell features

4. For patients who have not had an orchiectomy, there must be a plan to maintain
effective GnRH-analogue therapy for the duration of the trial

5. Serum testosterone level < 1.7 nmol/L (50 ng/dL) at the screening visit

6. Ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH)
analogue or orchiectomy (i.e., surgical or medical castration)

7. Progressive disease by PSA or imaging after docetaxel-based chemotherapy or
abiraterone in the setting of medical or surgical castration. Prior enzalutamide is
allowed as long as patients had a PSA response >50% or were treated for at least 6
months. Disease progression for study entry is defined by one or more of the following
three criteria:

- PSA progression defined by a minimum of three rising PSA levels with an interval
of = 1 week between each determination. The PSA value at the Screening visit
should be =2 µg/L (2 ng/mL)

- Soft tissue disease progression defined by RECIST (Appendix A)

- Bone disease progression defined by two or more new lesions on the bone scan

8. ECOG performance status of 0 or 1

9. Life expectancy of at least 6 months

10. Able to swallow the study drug and comply with study requirements

11. Acceptable liver function defined as:

- Total bilirubin = 1.5 times the upper limit of normal range (ULN)

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 3 times
ULN; however, = 5 times ULN in a subject who has liver metastases or has been
treated with biliary drainage

12. Acceptable renal function defined below:

• Serum creatinine = 1.5 times ULN

13. Acceptable hematologic status (without hematologic support including hematopoietic
factor, blood transfusion) defined below:

- Absolute neutrophil count (ANC) = 1,500/µL

- Platelet count = 100,000/µL

- Hemoglobin = 9.0 g/dL
Minimum age
18 Years
Maximum age
No limit
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

1. Treatment with AR antagonists (enzalutamide, bicalutamide, flutamide, nilutamide), 5-a
reductase inhibitors (finasteride, dutasteride), estrogens, or chemotherapy within 4
weeks of enrollment (day 1 visit) or plans to initiate treatment with any of these
drugs during the study. Ongoing therapy with bisphosphonates or Rank Ligand inhibitors
are acceptable.

2. Prior treatment with a PARP inhibitor or have plans to initiate treatment with a PARP
inhibitor during the study (only apply to subjects participating in Part 2b)

3. Treatment with therapeutic immunizations for prostate cancer (e.g., PROVENGE®) or
plans to initiate treatment with any of these therapies during the study

4. Metastases in the brain or active epidural disease (Note: patients with treated for
epidural disease are allowed to enter the trial)

5. Use of herbal products that may decrease PSA levels (e.g., saw palmetto) or systemic
corticosteroids greater than the equivalent of 10 mg of prednisone/prednisolone per
day within 4 weeks of enrollment (day 1 visit) or plans to initiate treatment with any
of these therapies during the study

6. History of another malignancy within the previous 5 years other than curatively
treated non-melanomatous skin cancer

7. Radiation therapy within 3 weeks (if single fraction of radiotherapy, then a 1-week
gap is allowable) and radionuclide therapy within 8 weeks of enrollment (Day 1 visit).
Any radiotherapy-related AE > Grade 1 before the start of study treatment.

8. Have used or plan to use from 30 days prior to enrollment (day 1 visit) through to the
end of the study medications known to lower the seizure threshold or prolong the
QT-interval (described in Appendix I)

9. Cardiac disease with New York Heart Association (NYHA) Class III or IV, including
congestive heart failure, myocardial infarction within 6 months prior to the trial
entry, unstable arrhythmia, or symptomatic peripheral arterial vascular disease

10. Severe concurrent disease, infection, or co-morbidity that, in the judgment of the
investigator, would make the patient inappropriate for enrollment

11. History of seizure, including any febrile seizure, loss of consciousness, or transient
ischemic attack within 12 months of enrollment (day 1 visit), or any condition that
may pre-dispose to seizure (e.g., prior stroke, brain arteriovenous malformation, head
trauma with loss of consciousness requiring hospitalization)

12. Use of an investigational agent within 4 weeks of enrollment or plans to initiate
treatment with an investigational agent during the study

13. Major surgery, other than diagnostic surgery, within 4 weeks prior to trial entry,
without complete recovery

14. Gastrointestinal disorder affecting absorption (e.g., gastrectomy, active peptic ulcer
disease within the last 3 months)

15. Structurally unstable bone lesions suggesting impending fracture

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 0 0
Border Medical Oncology - Albury
Recruitment hospital [2] 0 0
Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [3] 0 0
St George Hospital - Kogarah
Recruitment hospital [4] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [5] 0 0
Westmead Hospital - Sydney
Recruitment hospital [6] 0 0
Icon Cancer Centre - South Brisbane
Recruitment postcode(s) [1] 0 0
2640 - Albury
Recruitment postcode(s) [2] 0 0
2050 - Camperdown
Recruitment postcode(s) [3] 0 0
2217 - Kogarah
Recruitment postcode(s) [4] 0 0
2170 - Liverpool
Recruitment postcode(s) [5] 0 0
2145 - Sydney
Recruitment postcode(s) [6] 0 0
4101 - South Brisbane

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Atridia Pty Ltd.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a multicenter, dose-escalation/expansion phase 1 trial to evaluate the safety,
tolerability and efficacy of SHR3680 with or without SHR3162 given orally to subjects with
metastatic castration-resistant prostate cancer (mCRPC).
Trial website
https://clinicaltrials.gov/show/NCT02747342
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications