Endometrial Cancer RecurrentPhase 2NCT03485729
ONC201 in Recurrent or Metastatic Type II Endometrial Cancer Endometrial Cancer
A Phase 2 study testing Dordaviprone (ONC201) in people with Endometrial Cancer Recurrent, run by Jazz Pharmaceuticals at 3 sites in United States.
Trial summary
This was a Phase 2, Simon two-stage, non-randomized, open-label, 2-arm trial of dordaviprone (ONC201) in women with metastatic or recurrent Type II endometrial cancer who failed at least 1 prior chemotherapy regimen. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Endometrial Cancer Recurrent
- What is being tested?
- Dordaviprone (ONC201)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 3 sitesUnited States
- Study dates
- 21 Mar 2018to 19 Jan 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- A patient had to meet all of the following criteria to be eligible to participate in the study:
- Had histologically confirmed metastatic or recurrent Type II endometrial cancer (serous, clear cell, carcinosarcoma, adenosquamous, and mixed histologies). For patients with tumors that had mixed histologies, the tumor should have had evidence of some tumor cells with Type II endometrial cancer features.
- Must have had measurable disease, defined as at least 1 lesion that could be accurately measured in at least 1 dimension in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
- Had availability of at least 12 unstained slides from archival formalin-fixed paraffin-embedded (FFPE) tumor tissue. Available archived tissue biopsies were provided for correlative studies.
- For Arm A and Arm C, patients must have had disease that was amendable to biopsy and must have been willing to provide consent for a tumor biopsy at baseline (within 30 days of beginning ONC201) an at least 1 on-treatment tumor biopsy.
- Must have had radiographic disease progression after at least 1 line of systemic cytotoxic therapy for metastatic disease or with progression within 12 months of completing adjuvant chemotherapy.
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- Were aged ≥18 years.
- Had an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
- Must have had adequate bone marrow, hepatic and renal function, as defined below:
- Leukocytes: ≥3000/mcL
- Absolute neutrophil count: ≥1500/mcL
- Platelets: ≥100,000/mcL
- Total bilirubin: ≤1.5 upper limit of normal (ULN)
- Aspartate aminotransferase/Alanine aminotransferase (SGOT/SGPT): ≤2 ULN
- Creatinine: ≤1.5 ULN OR
- Creatinine clearance: ≥60 mL/min/1.732 for patients with creatinine levels above ULN calculated using Calvert formula
- Had a life expectancy of at least 3 months.
- Had the ability to understand and willingness to sign a written informed consent and Health Insurance Portability and Accountability Act (HIPAA) consent document.
- Must have been surgically sterile or postmenopausal or must have agreed to use effective contraception during the period of the trial and for at least 90 days after completion of treatment.
Who cannot join
- A potential patient who met any of the following criteria was ineligible to participate in the study:
- Had any prior treatment with ONC201.
- Had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who had not recovered from adverse events (AEs) due to agents administered more than 4 weeks earlier.
- Patients who had not recovered to baseline or Common Terminology Criteria for Adverse Events (CTCAE) Grade ≤2 from related toxicity to all prior therapies were excluded. Patients with non-serious AEs such as alopecia, fatigue, weakness, loss of appetite, and nausea that were non-significant were not excluded.
- Had any other prior malignancy from which the patient had been disease-free for less than 3 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of any site.
- Were unable to swallow capsules.
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- Had impairment of gastrointestinal (GI) function or GI disease that may have significantly altered the absorption of ONC201 (uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
- Were receiving any other investigational agents.
- Patients with symptomatic brain metastases were excluded. Patients with asymptomatic and treated central nervous system (CNS) metastases may have participated in this trial. The patient must have completed any prior treatment for CNS metastases >28 days prior to study entry including radiotherapy or surgery. Steroids for the treatment of brain metastasis were not permitted, and patients must have been stable off steroid treatment for 4 weeks prior to enrollment.
- Had uncontrolled intercurrent illness including but not limited to ongoing or active infection. Or any of the following in the 6 months previous to enrollment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism.
- Had active inflammatory GI disease, chronic diarrhea (unless related to underlying malignancy or prior related treatment) or history of abdominal fistula, GI perforation, peptic ulcer disease, or intra-abdominal abscess within 6 months prior to study enrollment. Gastroesophageal reflux disease under treatment with proton pump inhibitors was allowed.
- Known human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy.
- Had active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may have increased the risk associated with study participation or study drug administration or may have interfered with the interpretation of study results, or in the judgement of the Investigator, would have made the patient inappropriate for entry into the study.
- Were pregnant or breast feeding.
- Had known history of cardiac arrhythmias including atrial fibrillation, tachyarrhythmias, or bradycardia, unless arrhythmia was controlled and after cardiology had cleared patient to receive ONC201. Was receiving therapeutic agents known to prolong QT interval; however, the use of Zofran was permitted. Had a history of congestive heart failure or myocardial infarction or stroke in the 3 months prior to enrollment.
- Concomitant use of potent cytochrome P450 (CYP) A4/5 inhibitors or inducers during the treatment phase of the study and within 2 hours prior to starting study drug administration.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
Rutgers, The State University of New Jersey
New Brunswick, New Jersey, 08903
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
About this study
Official title: A Phase II Study of ONC201 in Recurrent or Metastatic Type II Endometrial Cancer
This was a Phase 2, Simon two-stage, non-randomized, open-label, 2-arm trial of dordaviprone (ONC201) in women with metastatic or recurrent Type II endometrial cancer who failed at least 1 prior chemotherapy regimen. Patients with histologically confirmed Type II endometrial cancer, including but not limited to serous, clear cell, carcinosarcoma, adenosquamous, and mixed histologies were eligible.
The primary objective of this study was to determine the efficacy of dordaviprone (ONC201) in metastatic type II endometrial cancer.
Note: This study was completed by predecessor company, Oncoceutics, Inc.
Read the detailed description
This study included 3 arms: Arm A, Arm B, and Arm C. Dordaviprone (ONC201) was to be administered as a dose of 625 mg by mouth, once or twice each week until disease progression, unacceptable toxicity, or if the patient discontinued for any other reason.
For Arm A and Arm B, ONC201 administration occurred on Days 1, 8, and 15 of each 3-week cycle. For Arm C, ONC201 administration occurred on Days 1, 2, 8, 9, and 15, and 16 of each 3-week cycle.
All patients in Arm A had a biopsy of their tumor one day after the second dose of dordaviprone (ONC201) on Cycle 1, Day 9. All patients in Arm C had a biopsy of their tumor one day after the fourth dose of dordaviprone (ONC201) on Cycle 1, Day 10.
Assessments of objective tumor response were conducted using RECIST version 1.1. Safety was assessed through the reporting of adverse events, measurement of vital signs, electrocardiograms, and clinical laboratory results.
Before the study was terminated, a total of 27 patients were enrolled and received at least 1 dose of dordaviprone (ONC201): 10 patients in Arm A, 14 patients in Arm B, and 3 patients in Arm C.
- Conditions
- Endometrial Cancer Recurrent
- Being tested
- Dordaviprone (ONC201)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dordaviprone (ONC201)Drug
625 mg dordaviprone (ONC201)
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | Patients received 625 mg dordaviprone (ONC201) once weekly on Days 1, 8, and 15 of each 3-week cycle. Patients were required to undergo a biopsy of their tumor one day after their second dose of dordaviprone (ONC201) on Cycle 1, Day 9. Receives: Drug: Dordaviprone (ONC201) |
| Arm B | Experimental | Patients received 625 mg dordaviprone (ONC201) once weekly on Days 1, 8, and 15 of each 3-week cycle. Patients were not required to undergo a biopsy of their tumor. Receives: Drug: Dordaviprone (ONC201) |
| Arm C | Experimental | Patients received 625 mg dordaviprone (ONC201) twice weekly on consecutive days on Days 1, 2, 8, 9, 15, and 16 of each 3-week cycle. Patients were required to undergo a biopsy of their tumor one day after their fourth dose of dordaviprone (ONC201) on Cycle 1, Day 10. Receives: Drug: Dordaviprone (ONC201) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-Free Survival Rate at 2 Months
Progression-free survival rate at 2 months was defined as the percentage of participants who exhibited progression-free survival for >8 weeks (>56 days) following treatment initiation; only Arm B participants were analyzed for this outcome.
Measured: 2 months (8 weeks); from treatment initiation to 2 months (8 weeks) following treatment initiation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2018
- Study start21 Mar 2018
- Primary completion19 Jan 2023
- Study completion19 Jan 2023
Why it stopped: This study was terminated due to a change in the Sponsor's corporate priorities. The decision to terminate the study was not based on any safety concerns.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Endometrial Cancer RecurrentStudies of the same condition, open and under way.
- More trials run by Jazz PharmaceuticalsThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jazz Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Oncoceutics, Inc.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03485729
- Sponsor's protocol ID
- ONC012
- Status last verified
- Dec 2024
- First submitted
- 25 Mar 2018
- Last updated
- 24 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of ONC201 in Recurrent or Metastatic Type II Endometrial Cancer
- ClinicalTrials.gov ID
- NCT03485729
- Acronym / sponsor ID
- ONC012
- Conditions
- Endometrial Cancer Recurrent
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: This study was terminated due to a change in the Sponsor's corporate priorities. The decision to terminate the study was not based on any safety concerns.
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Jazz PharmaceuticalsIndustry (pharma, biotech, devices)
- Collaborators
- Oncoceutics, Inc.
- Study start
- 21 Mar 2018 (actual)
- Primary completion
- 19 Jan 2023 (actual)
- Study completion
- 19 Jan 2023 (actual)
- First posted
- 2 Apr 2018 (actual)
- Results
- Posted 24 Dec 2024
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 2, Simon two-stage, non-randomized, open-label, 2-arm trial of dordaviprone (ONC201) in women with metastatic or recurrent Type II endometrial cancer who failed at least 1 prior chemotherapy regimen. Patients with histologically confirmed Type II endometrial cancer, including but not limited to serous, clear cell, carcinosarcoma, adenosquamous, and mixed histologies were eligible.
The primary objective of this study was to determine the efficacy of dordaviprone (ONC201) in metastatic type II endometrial cancer.
Note: This study was completed by predecessor company, Oncoceutics, Inc.
Detailed description
This study included 3 arms: Arm A, Arm B, and Arm C. Dordaviprone (ONC201) was to be administered as a dose of 625 mg by mouth, once or twice each week until disease progression, unacceptable toxicity, or if the patient discontinued for any other reason.
For Arm A and Arm B, ONC201 administration occurred on Days 1, 8, and 15 of each 3-week cycle. For Arm C, ONC201 administration occurred on Days 1, 2, 8, 9, and 15, and 16 of each 3-week cycle.
All patients in Arm A had a biopsy of their tumor one day after the second dose of dordaviprone (ONC201) on Cycle 1, Day 9. All patients in Arm C had a biopsy of their tumor one day after the fourth dose of dordaviprone (ONC201) on Cycle 1, Day 10.
Assessments of objective tumor response were conducted using RECIST version 1.1. Safety was assessed through the reporting of adverse events, measurement of vital signs, electrocardiograms, and clinical laboratory results.
Before the study was terminated, a total of 27 patients were enrolled and received at least 1 dose of dordaviprone (ONC201): 10 patients in Arm A, 14 patients in Arm B, and 3 patients in Arm C.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm A | Experimental | Drug: Dordaviprone (ONC201)Patients received 625 mg dordaviprone (ONC201) once weekly on Days 1, 8, and 15 of each 3-week cycle. Patients were required to undergo a biopsy of their tumor one day after their second dose of dordaviprone (ONC201) on Cycle 1, Day 9. |
| Arm B | Experimental | Drug: Dordaviprone (ONC201)Patients received 625 mg dordaviprone (ONC201) once weekly on Days 1, 8, and 15 of each 3-week cycle. Patients were not required to undergo a biopsy of their tumor. |
| Arm C | Experimental | Drug: Dordaviprone (ONC201)Patients received 625 mg dordaviprone (ONC201) twice weekly on consecutive days on Days 1, 2, 8, 9, 15, and 16 of each 3-week cycle. Patients were required to undergo a biopsy of their tumor one day after their fourth dose of dordaviprone (ONC201) on Cycle 1, Day 10. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- A patient had to meet all of the following criteria to be eligible to participate in the study:
- Had histologically confirmed metastatic or recurrent Type II endometrial cancer (serous, clear cell, carcinosarcoma, adenosquamous, and mixed histologies). For patients with tumors that had mixed histologies, the tumor should have had evidence of some tumor cells with Type II endometrial cancer features.
- Must have had measurable disease, defined as at least 1 lesion that could be accurately measured in at least 1 dimension in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
- Had availability of at least 12 unstained slides from archival formalin-fixed paraffin-embedded (FFPE) tumor tissue. Available archived tissue biopsies were provided for correlative studies.
- For Arm A and Arm C, patients must have had disease that was amendable to biopsy and must have been willing to provide consent for a tumor biopsy at baseline (within 30 days of beginning ONC201) an at least 1 on-treatment tumor biopsy.
Key exclusion criteria (16 listed)
- A potential patient who met any of the following criteria was ineligible to participate in the study:
- Had any prior treatment with ONC201.
- Had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who had not recovered from adverse events (AEs) due to agents administered more than 4 weeks earlier.
- Patients who had not recovered to baseline or Common Terminology Criteria for Adverse Events (CTCAE) Grade ≤2 from related toxicity to all prior therapies were excluded. Patients with non-serious AEs such as alopecia, fatigue, weakness, loss of appetite, and nausea that were non-significant were not excluded.
- Had any other prior malignancy from which the patient had been disease-free for less than 3 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of any site.
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 |
|---|---|---|
| Dordaviprone (ONC201)625 mg dordaviprone (ONC201) | Drug | Arm A, Arm B, Arm C |
Primary outcome
Progression-Free Survival Rate at 2 Months
Time frame: 2 months (8 weeks); from treatment initiation to 2 months (8 weeks) following treatment initiation
Progression-free survival rate at 2 months was defined as the percentage of participants who exhibited progression-free survival for >8 weeks (>56 days) following treatment initiation; only Arm B participants were analyzed for this outcome.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dordaviprone (ONC201) in people with Endometrial Cancer Recurrent, run by Jazz Pharmaceuticals at 3 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 19 inclusion and 16 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: stopped early, as of the sponsor's last update on 24 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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 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?
Yes. Results are posted in the registry (first posted 24 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Progression-Free Survival Rate at 2 Months (time frame: 2 months (8 weeks); from treatment initiation to 2 months (8 weeks) following treatment initiation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 24 Dec 2024; AzTrials last refreshed its copy on 7 Nov 2026.