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NeoplasmPhase 1NCT02747342

A Phase 1 Trial of SHR3680 With or Without SHR3162 in Prostate Cancer

A Phase 1 study testing SHR3680; SHR3162 in people with Neoplasm and Prostate Cancer, run by Atridia Pty Ltd. at 6 sites in Australia.

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

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). Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Neoplasm, Prostate Cancer
What is being tested?
SHR3680; SHR3162
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
33 participants
Where
6 sitesAustralia
Study dates
Sep 2016to 28 Jun 2020
Phase
Phase 1
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

  • Male 18 years and older
  • 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
  • Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features
  • 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
  • Serum testosterone level < 1.7 nmol/L (50 ng/dL) at the screening visit
  • Ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analogue or orchiectomy (i.e., surgical or medical castration)
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  • 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
  • ECOG performance status of 0 or 1
  • Life expectancy of at least 6 months
  • Able to swallow the study drug and comply with study requirements
  • 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
  • Acceptable renal function defined below:
  • Serum creatinine ≤ 1.5 times ULN
  • 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

Who cannot join

  • Treatment with AR antagonists (enzalutamide, bicalutamide, flutamide, nilutamide), 5-α 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.
  • 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)
  • Treatment with therapeutic immunizations for prostate cancer (e.g., PROVENGE®) or plans to initiate treatment with any of these therapies during the study
  • Metastases in the brain or active epidural disease (Note: patients with treated for epidural disease are allowed to enter the trial)
  • 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
  • History of another malignancy within the previous 5 years other than curatively treated non-melanomatous skin cancer
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  • 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.
  • 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)
  • 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
  • Severe concurrent disease, infection, or co-morbidity that, in the judgment of the investigator, would make the patient inappropriate for enrollment
  • 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)
  • Use of an investigational agent within 4 weeks of enrollment or plans to initiate treatment with an investigational agent during the study
  • Major surgery, other than diagnostic surgery, within 4 weeks prior to trial entry, without complete recovery
  • Gastrointestinal disorder affecting absorption (e.g., gastrectomy, active peptic ulcer disease within the last 3 months)
  • Structurally unstable bone lesions suggesting impending fracture

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

Australia6 sites

  • Border Medical Oncology

    Albury, New South Wales, 2640

  • Chris O'Brien Lifehouse

    Camperdown, New South Wales, 2050

  • St George Hospital

    Kogarah, New South Wales, 2217

  • Liverpool Hospital

    Liverpool, New South Wales, 2170

  • Icon Cancer Centre

    South Brisbane, Queensland, 4101

  • Westmead Hospital

    Sydney, New South Wales, 2145

Other trials in Australia

About this study

Official title: A Phase 1 Trial of SHR3680 With or Without SHR3162 in Subjects With Metastatic Castration-Resistant Prostate Cancer

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).

Read the detailed description

This study consists of 2 Part. In the Part 1 (dose escalation phase), up to 4 dose levels of SHR3680 will be investigated with a sequential "3+3" design (3 or 6 participants in each dose level). There will be a single-dose pharmacokinetic (PK) run-in period (7 days). Following the first dose, participants will enter a 1 week treatment-free period to evaluate safety and single-dose PK. If not dose-limiting toxicities (DLTs) are observed during the 1-week period, SHR3680 administration will resume at the same dose level.

In the Part 2a (expansion phase), up to 9 additional participants will be enrolled at the MTD or recommended phase 2 dose (RP2D). The purpose of the expansion part of the study is to explore the clinical benefits of SHR3680 and to further identify its PK features.

In Part 2b (combination phase), two dose cohorts of SHR3162 combine with SHR3680 at fixed dose will be investigated.

Being tested
SHR3680; SHR3162
Keywords
Metastatic castration-resistant prostate cancer
Medical subject headings
Neoplasms, Prostatic Neoplasms

What participants receive

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

  • SHR3680; SHR3162Drug

    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.

Study groups in NCT02747342
Study groupRoleWhat they receive
SHR3680; SHR3680+SHR3162ExperimentalIn dose esclation and expansion phase, SHR3680 will be administered orally In combination phase, SHR3680 will be administered together with SHR3162
Receives: Drug: SHR3680; SHR3162

What is being measured

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

  1. 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

    Measured: 4 weeks

  2. Recommended Phase 2 doses (RP2Ds)

    RP2D will be determined based on the available data for toxicity and PK.

    Measured: 24 months

Secondary outcomes (7)

  1. 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.

    Measured: 24 months

  2. The AUC of SHR3680 and SHR3162 (area under the curve)

    The AUC of SHR3680 given as BID 240 mg tablets in combination with SHR3162

    Measured: 4 weeks

  3. 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

    Measured: 4 weeks

  4. PSA reduction

    Percentage of participants reaching at least a 50% reduction in prostate specific antigen (PSA) at Week 12 as compared to baseline

    Measured: 12 weeks

  5. PSA progression

    Time to reach the PSA Progression

    Measured: 24 months

  6. 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

    Measured: 24 months

  7. Radiological progression-free survival (PFS)

    the length of time during and after the treatment

    Measured: 24 months

Timeline

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

  1. First posted21 Apr 2016 (estimated)
  2. Study startSep 2016
  3. Primary completion28 Jun 2019
  4. Study completion28 Jun 2020

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
33 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02747342
Sponsor's protocol ID
SHR3680-002
Status last verified
Jul 2020
First submitted
19 Apr 2016
Last updated
21 Jul 2020
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing SHR3680; SHR3162 in people with Neoplasm and Prostate Cancer, run by Atridia Pty Ltd. at 6 sites in Australia.

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 22 inclusion and 15 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 21 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Australia. 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 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.

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?

Maximum tolerated dose (MTD) (time frame: 4 weeks). 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 NCT02747342.

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 Jul 2020.

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