Endometrial CancerPhase 2NCT03099499
Single Agent ONC201 in Recurrent or Metastatic Endometrial Cancer
A Phase 2 study testing ONC201 in people with Endometrial Cancer, run by Fox Chase Cancer Center at 1 site in United States.
Trial summary
ONC201 is a small molecule which selectively targets the G protein-coupled receptor DRD2. Downstream of target engagement, ONC201 activates the integrated stress response (ISR) in tumor cell leading to inactivation of Akt and extracellular signal-regulated kinase (ERK) signaling as well as induction of the TRAIL… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Endometrial Cancer
- What is being tested?
- ONC201
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Jun 2017to 9 Sep 2020
- 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
- Patients must have histologically confirmed metastatic or recurrent endometrial cancer. Eligible histologies include but are not limited to endometrioid, serous, clear cell, carcinosarcoma, adenosquamous, and mixed histologies.
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension in accordance with RECIST criteria v. 1.1
- Must have radiographic disease progression after 1 line of systemic cytotoxic therapy for metastatic disease or with progression within 12 months of completing adjuvant chemotherapy
- Available archived tissue biopsies will be provided for correlative studies
- Age > 18 years.
- Eastern Cooperative Oncology group (ECOG) performance status of 0, 1, or 2
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- Patients must have adequate bone marrow, hepatic and renal function as defined below:
- Leukocytes > 3,000/micro-liter (mcl)
- Absolute neutrophil count > 1,500/mcL
- Platelets > 100,000/mcL
- Total bilirubin ≤1.5 upper limit of normal (ULN)
- Aspartate aminotransferase/ Alanine aminotransferase (AST/ALT) < 2 ULN
- Creatinine ≤1.5 ULN OR
- Creatinine clearance > 60 Ml/min/1.73 m2 for patients with creatinine levels above ULN calculated using Calvert formula
- Prior chemotherapy, hormonal and radiation therapy administered in the adjuvant setting will be allowed.
- Life expectancy at least 3 months
- Ability to understand and willingness to sign a written informed consent and HIPAA consent document
- Patients must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of the trial and for at least 90 days after completion of treatment.
Who cannot join
- No prior treatment with ONC201
- Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- The subjects who have not recovered to baseline or CTCAE ≤ Grade 1 from related toxicity to all prior therapies will be excluded. Patients with Non-serious adverse events such as alopecia, fatigue, weakness, loss of appetite and nausea that are non-significant will not be excluded.
- Any other prior malignancy from which the patient has 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.
- The subject is unable to swallow capsules
- Patients receiving any other investigational agents
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- Patients with symptomatic brain metastases are excluded. Patients with asymptomatic and treated central nervous system (CNS) metastases may participate 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 are not permitted, and patients must be stable off steroid treatment for 4 weeks prior to enrollment
- Uncontrolled inter-current illness including, but not limited to ongoing or active infection. Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, cerebrovascular accident, transient ischemic attack or symptomatic pulmonary embolism.
- Active inflammatory gastrointestinal disease, chronic diarrhea (unless related to underlying malignancy or prior related treatment) or history of abdominal fistula, gastrointestinal perforation, peptic ulcer disease, or intra-abdominal abscess within 6 months prior to study enrollment. Gastroesophageal reflux disease under treatment with proton pump inhibitors is allowed.
- Known Human Immunodeficiency Virus (HIV)-positive patients on combination antiretroviral therapy
- Known history of Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) infection.
- Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, or in the judgment of the investigator would make the patient inappropriate for entry into the study.
- Pregnant or breast feeding. Refer to section 4.4 for further details.
Trial locations and contacts
1 site in 1 country.
United States1 site
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
About this study
Official title: A Phase 2 Study of Single Agent ONC201 in Recurrent or Metastatic Endometrial Cancer
ONC201 is a small molecule which selectively targets the G protein-coupled receptor DRD2. Downstream of target engagement, ONC201 activates the integrated stress response (ISR) in tumor cell leading to inactivation of Akt and extracellular signal-regulated kinase (ERK) signaling as well as induction of the TRAIL pathway. ONC201 also inhibits dopamine receptor 2 (DRD2), resulting in anti-tumor responses in preclinical models. Single agent ONC201 has been examined in open-label Phase I studies in patients with advanced, treatment refractory solid malignancies. Due to its differential anti-proliferative and pro-apoptotic response in tumor cells, treatment was overall well tolerated, and the recommended phase II dose of ONC201 was set at 625mg every three weeks. An additional dose-escalation phase I study (NCT02609230) is further evaluating weekly versus three week dosing in patients with advanced solid tumors and multiple myeloma. Preliminary data from these phase I studies suggests a possible clinical benefit in patients with advanced, chemo-refractory endometrial cancers, with at least one mixed response noted in a patient with clear cell histology.
Hypothesis: Single agent ONC201 will demonstrate clinical benefit in women with recurrent or metastatic endometrial cancers, especially in those women with alterations in the Phosphoinositide 3 kinase (PI3K)/Akt/mammalian target of Rapamycin (mTOR) pathway.
- Conditions
- Endometrial Cancer
- Being tested
- ONC201
- Medical subject headings
- Endometrial Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ONC201Drug
ONC201 will be administered at a dose of 625 mg by mouth weekly until disease progression, unacceptable toxicity, or if the patient discontinues for any other reason. Radiologic tumor assessment would be performed at baseline, Cycle 3 Day 1, Cycle 5 Day 1, and at the end of every 3 cycles beyond cycle 5. All patients including those removed from the study due to unacceptable toxicity, will undergo radiologic tumor assessment at the time of discontinuation (End of treatment).
| Study group | Role | What they receive |
|---|---|---|
| ONC201 treatment Arm | Experimental | Not described Receives: Drug: ONC201 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival (PFS) Rate at 12 Weeks
PFS will be calculated from the day of starting the treatment until 12 weeks. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Measured: 12 weeks
Objective Response Rate (ORR) as Determined by Response Criteria In Solid Tumors (RECIST) 1.1 Criteria
ORR will be calculated from the day of starting the treatment until disease progression. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Measured: 1-2 years
Secondary outcomes (3)
Duration of Response
Duration of response will be determined from the time when a partial or complete response is seen until disease progression
Measured: 1-2 years
Duration of Stable Disease
Duration of stable disease will be calculated from the time of first treatment until disease progression
Measured: 1-2 years
Median Progression Free Survival
Progression free survival will be calculated from the time of the start of the treatment until disease progression. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Measured: 1-2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2017
- Study start8 Jun 2017
- Primary completion9 Sep 2020
- Study completion9 Sep 2020
Why it stopped: Slow accrual
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 CancerStudies of the same condition, open and under way.
- More trials run by Fox Chase Cancer CenterThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fox Chase Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Oncoceutics, Inc.
- Responsible party
- Sponsor
- Investigators
- Gina Mantia-Smaldone, MD, Principal investigator, Fox Chase Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03099499
- Sponsor's protocol ID
- GYN-106
- Status last verified
- Oct 2026
- First submitted
- 23 Mar 2017
- Last updated
- 3 Nov 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of Single Agent ONC201 in Recurrent or Metastatic Endometrial Cancer
- ClinicalTrials.gov ID
- NCT03099499
- Acronym / sponsor ID
- GYN-106
- Conditions
- Endometrial Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow accrual
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Fox Chase Cancer CenterUniversity, hospital or other
- Collaborators
- Oncoceutics, Inc.
- Study start
- 8 Jun 2017 (actual)
- Primary completion
- 9 Sep 2020 (actual)
- Study completion
- 9 Sep 2020 (actual)
- First posted
- 4 Apr 2017 (actual)
- Results
- Posted 14 Oct 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
ONC201 is a small molecule which selectively targets the G protein-coupled receptor DRD2. Downstream of target engagement, ONC201 activates the integrated stress response (ISR) in tumor cell leading to inactivation of Akt and extracellular signal-regulated kinase (ERK) signaling as well as induction of the TRAIL pathway. ONC201 also inhibits dopamine receptor 2 (DRD2), resulting in anti-tumor responses in preclinical models. Single agent ONC201 has been examined in open-label Phase I studies in patients with advanced, treatment refractory solid malignancies. Due to its differential anti-proliferative and pro-apoptotic response in tumor cells, treatment was overall well tolerated, and the recommended phase II dose of ONC201 was set at 625mg every three weeks. An additional dose-escalation phase I study (NCT02609230) is further evaluating weekly versus three week dosing in patients with advanced solid tumors and multiple myeloma. Preliminary data from these phase I studies suggests a possible clinical benefit in patients with advanced, chemo-refractory endometrial cancers, with at least one mixed response noted in a patient with clear cell histology.
Hypothesis: Single agent ONC201 will demonstrate clinical benefit in women with recurrent or metastatic endometrial cancers, especially in those women with alterations in the Phosphoinositide 3 kinase (PI3K)/Akt/mammalian target of Rapamycin (mTOR) pathway.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ONC201 treatment Arm | Experimental | Drug: ONC201 |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Patients must have histologically confirmed metastatic or recurrent endometrial cancer. Eligible histologies include but are not limited to endometrioid, serous, clear cell, carcinosarcoma, adenosquamous, and mixed histologies.
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension in accordance with RECIST criteria v. 1.1
- Must have radiographic disease progression after 1 line of systemic cytotoxic therapy for metastatic disease or with progression within 12 months of completing adjuvant chemotherapy
- Available archived tissue biopsies will be provided for correlative studies
- Age > 18 years.
Key exclusion criteria (13 listed)
- No prior treatment with ONC201
- Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- The subjects who have not recovered to baseline or CTCAE ≤ Grade 1 from related toxicity to all prior therapies will be excluded. Patients with Non-serious adverse events such as alopecia, fatigue, weakness, loss of appetite and nausea that are non-significant will not be excluded.
- Any other prior malignancy from which the patient has 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.
- The subject is unable to swallow capsules
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 |
|---|---|---|
| ONC201ONC201 will be administered at a dose of 625 mg by mouth weekly until disease progression, unacceptable toxicity, or if the patient discontinues for any other reason. Radiologic tumor assessment would be performed at baseline, Cycle 3 Day 1, Cycle 5 Day 1, and at the end of every 3 cycles beyond cycle 5. All patients including those removed from the study due to unacceptable toxicity, will undergo radiologic tumor assessment at the time of discontinuation (End of treatment). | Drug | ONC201 treatment Arm |
Primary outcome
Progression Free Survival (PFS) Rate at 12 Weeks
Time frame: 12 weeks
PFS will be calculated from the day of starting the treatment until 12 weeks. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Objective Response Rate (ORR) as Determined by Response Criteria In Solid Tumors (RECIST) 1.1 Criteria
Time frame: 1-2 years
ORR will be calculated from the day of starting the treatment until disease progression. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
3 secondary outcomes
Duration of Response
Time frame: 1-2 years
Duration of Stable Disease
Time frame: 1-2 years
Median Progression Free Survival
Time frame: 1-2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Gina Mantia-Smaldone, MD principal investigator
Fox Chase Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ONC201 in people with Endometrial Cancer, run by Fox Chase Cancer Center at 1 site 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 18 inclusion and 13 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 3 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 14 Oct 2026). 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 (PFS) Rate at 12 Weeks (time frame: 12 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?
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 3 Nov 2026.