Metastatic Castrate Resistant Prostate Cancer (mCRPC)Phase 1NCT02826772
Safety, Tolerability, and PK of GT0918 (Proxalutamide) in Subjects With Metastatic Castrate Prostate Cancer
A Phase 1 study testing GT0918 in people with Metastatic Castrate Resistant Prostate Cancer (mCRPC), run by Suzhou Kintor Pharmaceutical Inc, at 6 sites in United States.
Trial summary
This was a Phase 1, multicenter, open-label, clinical trial in adult subjects with metastatic castrate resistant prostate cancer who progressed after both hormonal therapy (abiraterone or enzalutamide) and chemotherapy (docetaxel), or cannot tolerate either or both therapies. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Metastatic Castrate Resistant Prostate Cancer (mCRPC)
- What is being tested?
- GT0918
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 6 sitesUnited States
- Study dates
- 10 Feb 2016to 15 Feb 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
- Written informed consent obtained prior to any study-related procedure being performed.
- Subjects at least 18 years of age or older at the time of consent.
- Histologically confirmed metastatic castrate resistant cancer (mCRPC) who progressed after both hormonal therapy (abiraterone or enzalutamide) and chemotherapy (docetaxel, for example); or cannot tolerate either or both of these classes of therapies.
- Ongoing androgen deprivation therapy with a luteinizing hormone-releasing hormone (LHRH) "super-agonist" or antagonist, or bilateral orchiectomy and serum testosterone level < 50 ng/dL (< 0.5 ng/mL, < 1.7 nmol/L) at screening.
- Metastatic disease documented by computed tomography (CT)/magnetic resonance imaging (MRI) or bone scan.
- Progressive disease despite ongoing androgen deprivation or chemotherapy. Progressive disease is defined by 1 or more of the following criteria:
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- Subjects with a rising PSA value > 2 ng/mL in at least 2 measurements, at least 1 week apart. If the confirmatory PSA value is less than the screening PSA value, then an additional test for the rising PSA is required to document progression.
- Subjects with measurable disease, progression defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
- Subjects with metastatic bone disease, progression defined by 2 or more new lesions in a radionuclide bone scan.
- ECOG performance status of 0-2 (dose escalation phase); ECOG performance status of 0-1 (expansion phase).
- Screening blood counts of the following:
- Absolute neutrophil count ≥ 1500/μL
- Platelets ≥ 100,000/μL
- Hemoglobin > 9 g/dL
- Screening chemistry values of the following:
- Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 2.5 × upper limit of the normal reference range (ULN)
- Total bilirubin ≤ 2 × ULN
- Creatinine ≤ 1.5 × ULN
- Albumin > 2.8 g/dL.
- At screening, life expectancy of at least 3 months.
- Subjects whose partners are women of childbearing potential (WOCBP) must use an adequate method of birth control while on study drug and at least for 3 weeks after discontinuation of study drug.
- Subject is willing and able to comply with all protocol required visits and assessments.
Who cannot join
- Subjects with life expectancy less than 3 months.
- Discontinuation of bicalutamide or nilutamide less than 6 weeks, and other antiandrogens less than 4 weeks, abiraterone less than 3 weeks, prior to the start of study medication.
- Prior chemotherapy, radiation, sipuleucel-T or other experimental immunotherapy less than 4 weeks prior to the start of study medication.
- Prior chemotherapies more than 2 lines (Phase II part only) .
- Ongoing acute treatment-related toxicity associated with a previous therapy greater than grade 1 except for grade 2 alopecia or neuropathy.
- History of impaired adrenal gland function (eg, Addison's disease, Cushing's syndrome).
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- Known gastrointestinal disease or condition that affects the absorption of GT0918.
- History of congestive heart failure New York Heart Association (NYHA) class III or IV or uncontrolled hypertension at screening.
- History or family history of long QT syndrome.
- History of other malignancy within the previous 3 years, except basal cell or squamous cell carcinoma, or non-muscle invasive bladder cancer.
- Use of systemic glucocorticoid (eg, prednisone, dexamethasone) within 14 days prior to the start of study medication.
- Co-administration of CYP3A4 ligands that serve as substrates or induce or inhibit the enzyme.
- Prior use of any herbal products known to decrease PSA levels (eg, PC-SPES or saw palmetto) within 30 days prior to the start of study medication.
- Major surgery within 30 days prior to the start of study medication.
- Blood transfusion (including blood products) within 1 week of screening.
- Serious persistent infection within 14 days prior to the start of study medication.
- Serious concurrent medical condition including CNS disorders.
- Previous history of difficulty swallowing capsules.
- Known hypersensitivity to GT0918 or its excipients.
- Any condition that, in the opinion of the investigator, would impair the subject's ability to comply with study procedures.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Gabrail Cancer Center Research
Canton, Ohio, 44718
North Shore Hematology Oncology Associates
East Setauket, New York, 11733
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, 89169
Rutgers University
New Brunswick, New Jersey, 08901
G U Research Network
Omaha, Nebraska, 68130
Chesapeake Urology Research Associates
Towson, Maryland, 21204
About this study
Official title: A Phase 1/2, Multi-Center, Open-Label, Two-Stage Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of GT0918 in Subjects With Metastatic Castrate Resistant Prostate Cancer (mCRPC)
This was a Phase 1, multicenter, open-label, clinical trial in adult subjects with metastatic castrate resistant prostate cancer who progressed after both hormonal therapy (abiraterone or enzalutamide) and chemotherapy (docetaxel), or cannot tolerate either or both therapies.
The study involved a Phase 1 dose escalation of oral GT0918 to evaluate its safety, tolerability, pharmacokinetics and pharmacodynamics.
Read the detailed description
GT0918 treatment was initiated with the first dose of 50 mg/day in a cohort of 3 patients, and 6- patients per cohort for the subsequent escalated dose levels at 100 mg, 200 mg, 300 mg, 400 mg, 500 mg and 600 mg/day. Patients received orally administered GT0918 once daily at the indicated doses for 28 consecutive days (4 weeks), followed by a 7-day off-treatment period for PK analysis. This concluded the Cycle 1 treatment. Patients who could not complete the first cycle of 28 days for DLT evaluation were to be considered as early termination and replaced. Upon completion of the Cycle 1 treatment, if no DLT occurred in the cohort of 3 patients, or no more than 1 patient had DLT in cohorts with at least 6 patients, dose escalation was allowed for the subsequent higher dose.
Patients were to receive up to 6 cycles of GT0918 treatments at their assigned dose levels if they were evaluated by the investigator to have no unacceptable toxicity and show evidence of clinical benefit (stable disease or a response) per RECIST v1.1 criteria and PSA assessments. No off-treatment periods were scheduled for the additional cycles from Cycle 2 beyond. Patients had to be evaluated bi-monthly for their eligibility to continue the treatment of additional cycles. Patient evaluations included CT and/or MRI scans performed every 2 cycles (8 weeks), as well as physical examinations, ECOG performance status, PSA measurements, which were performed every 4 weeks. Cycles beyond the 6th cycle were optional for eligible subjects that did not exhibit progressive disease (PD). Eligible patients could be treated for a total of 6 months at their assigned dose level at the investigator's discretion.
Patients would have an End-of-Study (EOS) visit if treatment were discontinued due to intolerable toxicities, disease progression, withdrawal of consent. Safety follow-up for possible delayed drug-related AE or side effects can be performed by phone call or office visit if needed.
- Being tested
- GT0918
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GT0918Drug
Also called androgen receptor antagonist, proxalutamide
anti-tumor activity
| Study group | Role | What they receive |
|---|---|---|
| Phase 1 GT0918 level 1 | Experimental | generic name: not applicable dosage form: tablet dosage: oral dosage to be determined dosage frequency: daily dosage duration: 6 months Receives: Drug: GT0918 |
What is being measured
The primary outcome is the main question the study is designed to answer.
dose-limiting toxicities (DLTs)
abnormal laboratory value
Measured: 1 month
maximum tolerated dose (MTD),biological dose or minimal effective dose, (MED), and recommended Phase 2 dose(s) (RP2D).
50 mg, 100 mg, 200 mg, 300 mg, 400 mg or 500 mg of GT0918
Measured: 1 month
Secondary outcomes (13)
maximum concentration (Cmax)
Pharmacokinetics
Measured: 6 months
time that maximum concentration is observed (tmax)
Pharmacokinetics
Measured: 6 months
area under the concentration time-curve from time zero to infinity (AUC0∞)
Pharmacokinetics
Measured: 6 months
area under the plasma concentration-time curve from time zero hours to time (t hrs), (AUC0-t)
Pharmacokinetics
Measured: 6 months
area under the plasma concentration-time curve from time zero hours to 24 hours (AUC0-24)
Pharmacokinetics
Measured: 6 months
terminal elimination rate constant (λz)
Pharmacokinetics
Measured: 6 months
terminal elimination half life (t½)
Pharmacokinetics
Measured: 6 months
volume of distribution (Vz)
Pharmacokinetics
Measured: 6 months
volume of plasma cleared of the drug per unit time (C)
Pharmacokinetics
Measured: 6 months
circulating tumor deoxyribonucleic acid (ctDNA)
antitumor activities
Measured: 6 months
circulating messenger ribonucleic acid (mRNA)
antitumor activities
Measured: 6 months
circulating tumor cells (CTC)
antitumor activities
Measured: 6 months
prostate-specific antigen (PSA)
biomarker
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2016 (estimated)
- Study start10 Feb 2016
- Primary completion15 May 2019
- Study completion15 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Castrate Resistant Prostate Cancer (mCRPC)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Suzhou Kintor Pharmaceutical Inc,
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Phoebe Zhang, PhD, Study director, Suzhou Kintor Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02826772
- Sponsor's protocol ID
- GT0918-US-1001
- Status last verified
- Mar 2020
- First submitted
- 23 Jun 2016
- Last updated
- 17 Mar 2020
- Results posted
- No
- Data monitoring committee
- 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
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2, Multi-Center, Open-Label, Two-Stage Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of GT0918 in Subjects With Metastatic Castrate Resistant Prostate Cancer (mCRPC)
- ClinicalTrials.gov ID
- NCT02826772
- Acronym / sponsor ID
- GT0918-US-1001
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Suzhou Kintor Pharmaceutical Inc,Industry (pharma, biotech, devices)
- Study start
- 10 Feb 2016 (actual)
- Primary completion
- 15 May 2019 (actual)
- Study completion
- 15 Feb 2020 (actual)
- First posted
- 11 Jul 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was a Phase 1, multicenter, open-label, clinical trial in adult subjects with metastatic castrate resistant prostate cancer who progressed after both hormonal therapy (abiraterone or enzalutamide) and chemotherapy (docetaxel), or cannot tolerate either or both therapies.
The study involved a Phase 1 dose escalation of oral GT0918 to evaluate its safety, tolerability, pharmacokinetics and pharmacodynamics.
Detailed description
GT0918 treatment was initiated with the first dose of 50 mg/day in a cohort of 3 patients, and 6- patients per cohort for the subsequent escalated dose levels at 100 mg, 200 mg, 300 mg, 400 mg, 500 mg and 600 mg/day. Patients received orally administered GT0918 once daily at the indicated doses for 28 consecutive days (4 weeks), followed by a 7-day off-treatment period for PK analysis. This concluded the Cycle 1 treatment. Patients who could not complete the first cycle of 28 days for DLT evaluation were to be considered as early termination and replaced. Upon completion of the Cycle 1 treatment, if no DLT occurred in the cohort of 3 patients, or no more than 1 patient had DLT in cohorts with at least 6 patients, dose escalation was allowed for the subsequent higher dose.
Patients were to receive up to 6 cycles of GT0918 treatments at their assigned dose levels if they were evaluated by the investigator to have no unacceptable toxicity and show evidence of clinical benefit (stable disease or a response) per RECIST v1.1 criteria and PSA assessments. No off-treatment periods were scheduled for the additional cycles from Cycle 2 beyond. Patients had to be evaluated bi-monthly for their eligibility to continue the treatment of additional cycles. Patient evaluations included CT and/or MRI scans performed every 2 cycles (8 weeks), as well as physical examinations, ECOG performance status, PSA measurements, which were performed every 4 weeks. Cycles beyond the 6th cycle were optional for eligible subjects that did not exhibit progressive disease (PD). Eligible patients could be treated for a total of 6 months at their assigned dose level at the investigator's discretion.
Patients would have an End-of-Study (EOS) visit if treatment were discontinued due to intolerable toxicities, disease progression, withdrawal of consent. Safety follow-up for possible delayed drug-related AE or side effects can be performed by phone call or office visit if needed.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Phase 1 GT0918 level 1 | Experimental | Drug: GT0918generic name: not applicable dosage form: tablet dosage: oral dosage to be determined dosage frequency: daily dosage duration: 6 months |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Written informed consent obtained prior to any study-related procedure being performed.
- Subjects at least 18 years of age or older at the time of consent.
- Histologically confirmed metastatic castrate resistant cancer (mCRPC) who progressed after both hormonal therapy (abiraterone or enzalutamide) and chemotherapy (docetaxel, for example); or cannot tolerate either or both of these classes of therapies.
- Ongoing androgen deprivation therapy with a luteinizing hormone-releasing hormone (LHRH) "super-agonist" or antagonist, or bilateral orchiectomy and serum testosterone level < 50 ng/dL (< 0.5 ng/mL, < 1.7 nmol/L) at screening.
- Metastatic disease documented by computed tomography (CT)/magnetic resonance imaging (MRI) or bone scan.
Key exclusion criteria (20 listed)
- Subjects with life expectancy less than 3 months.
- Discontinuation of bicalutamide or nilutamide less than 6 weeks, and other antiandrogens less than 4 weeks, abiraterone less than 3 weeks, prior to the start of study medication.
- Prior chemotherapy, radiation, sipuleucel-T or other experimental immunotherapy less than 4 weeks prior to the start of study medication.
- Prior chemotherapies more than 2 lines (Phase II part only) .
- Ongoing acute treatment-related toxicity associated with a previous therapy greater than grade 1 except for grade 2 alopecia or neuropathy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GT0918Also: androgen receptor antagonist, proxalutamideanti-tumor activity | Drug | Phase 1 GT0918 level 1 |
Primary outcome
dose-limiting toxicities (DLTs)
Time frame: 1 month
abnormal laboratory value
maximum tolerated dose (MTD),biological dose or minimal effective dose, (MED), and recommended Phase 2 dose(s) (RP2D).
Time frame: 1 month
50 mg, 100 mg, 200 mg, 300 mg, 400 mg or 500 mg of GT0918
13 secondary outcomes
maximum concentration (Cmax)
Time frame: 6 months
time that maximum concentration is observed (tmax)
Time frame: 6 months
area under the concentration time-curve from time zero to infinity (AUC0∞)
Time frame: 6 months
area under the plasma concentration-time curve from time zero hours to time (t hrs), (AUC0-t)
Time frame: 6 months
area under the plasma concentration-time curve from time zero hours to 24 hours (AUC0-24)
Time frame: 6 months
terminal elimination rate constant (λz)
Time frame: 6 months
terminal elimination half life (t½)
Time frame: 6 months
volume of distribution (Vz)
Time frame: 6 months
volume of plasma cleared of the drug per unit time (C)
Time frame: 6 months
circulating tumor deoxyribonucleic acid (ctDNA)
Time frame: 6 months
circulating messenger ribonucleic acid (mRNA)
Time frame: 6 months
circulating tumor cells (CTC)
Time frame: 6 months
prostate-specific antigen (PSA)
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2020.
- Derived from this study: PubMed 32203306Maia 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Phoebe Zhang, PhD study director
Suzhou Kintor Pharmaceuticals, Inc.
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GT0918 in people with Metastatic Castrate Resistant Prostate Cancer (mCRPC), run by Suzhou Kintor Pharmaceutical Inc, at 6 sites in United States.
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 20 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 17 Mar 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 United States. 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?
dose-limiting toxicities (DLTs) (time frame: 1 month). 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 NCT02826772, 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 17 Mar 2020.