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

NCT02747342 | Completed Phase 1

• 1 other identifier: SHR3680-002
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 6

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).

Conditions

Neoplasm; Prostate Cancer

Keywords

Metastatic castration-resistant prostate cancer

Outcome Measures

Primary Outcomes (2)

• 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

  4 weeks

• Recommended Phase 2 doses (RP2Ds)

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

  24 months

Secondary Outcomes (7)

• Number of participants with treatment-emergent adverse events

  24 months

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

  4 weeks

• The cMax (peak plasma concentration) of SHR3680 and SHR3162

  4 weeks

• PSA reduction

  12 weeks

• PSA progression

  24 months

Other Outcomes (1)

• Homologous recombination deficiency (HRD)

  2 weeks

Study Arms (1)

SHR3680; SHR3680+SHR3162

EXPERIMENTAL

In dose esclation and expansion phase, SHR3680 will be administered orally In combination phase, SHR3680 will be administered together with SHR3162

Drug: SHR3680; SHR3162

Interventions

SHR3680; SHR3162 DRUG

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.

SHR3680; SHR3680+SHR3162

Eligibility Criteria

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

You may qualify if:

• 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)
• 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)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Atridia Pty Ltd.: lead

Study Sites (6)

Border Medical Oncology

Albury, New South Wales, 2640, Australia

Location

Chris O'Brien Lifehouse

Camperdown, New South Wales, 2050, Australia

Location

St George Hospital

Kogarah, New South Wales, 2217, Australia

Location

Liverpool Hospital

Liverpool, New South Wales, 2170, Australia

Location

Westmead Hospital

Sydney, New South Wales, 2145, Australia

Location

Icon Cancer Centre

South Brisbane, Queensland, 4101, Australia

Location

MeSH Terms

Conditions

Neoplasms; Prostatic Neoplasms

Interventions

fluzoparib

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2016
• First Posted: April 21, 2016
• Study Start: September 1, 2016
• Primary Completion: June 28, 2019
• Study Completion: June 28, 2020
• Last Updated: July 21, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

AU (6)