Triple Negative Breast CancerPhase 2NCT03394027
ONC201 in Recurrent/Refractory Metastatic Breast Cancer and Advanced Endometrial Carcinoma
A Phase 2 study testing ONC201 in people with Triple Negative Breast Cancer and Endometrial Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Background: The new drug ONC201 have been shown to kill breast cancer and endometrial cancer cells in the laboratory. The exact mechanism of action is not completely clear yet, but the ONC201 destroys the mitochondria inside the cells. Blocking mitochondrial activity may kill tumor cells, which would shrink tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Triple Negative Breast Cancer, Endometrial Cancer, Hormone Receptor Positive, HER2 Negative Breast 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
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Jan 2018to 7 Oct 2021
- 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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have histologically or cytologically confirmed persistent or recurrent advanced or metastatic invasive endometrial cancer (EC) for which standard curative measures do not exist or are no longer effective.
- Patients must have measurable disease, per RECIST 1.1
- Patients must have at least one lesion deemed safe to biopsy and be willing to undergo mandatory biopsies.
- Women with endometrial cancer must have had at least one prior line of therapy in the metastatic/recurrent setting but there is no limit to the number of prior chemotherapy lines. Patients are eligible if they have received treatment with immunotherapy, such PD-1 inhibitors, PD-L1 inhibitors or CTLA4 inhibitors.
- Age greater than or equal to 18 years.
- ECOG performance status 0 or 1
- Adequate renal function, defined as serum creatinine less than or equal to 1.5 X upper limit of normal (ULN), or measured creatinine clearance greater than or equal to 60 mL/min/1.
- Adequate hepatic function, defined as AST and ALT levels less than or equal to 3 X ULN and total bilirubin < 1.5 X ULN, unless known diagnosis of Gilbert's syndrome, where bilirubin less than or equal to 5 mg/dl will be permitted. Gilbert's syndrome will be defined as elevated unconjugated bilirubin, with conjugated (direct) bilirubin within the normal range and less than 20% of the total. Total bilirubin will be permitted up to 5 mg/dL, if patients have historical readings consistent with...
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: A Phase 2 Study of ONC201 in Recurrent/Refractory Metastatic Breast Cancer and Advanced Endometrial Carcinoma
Background:
The new drug ONC201 have been shown to kill breast cancer and endometrial cancer cells in the laboratory. The exact mechanism of action is not completely clear yet, but the ONC201 destroys the mitochondria inside the cells. Blocking mitochondrial activity may kill tumor cells, which would shrink tumors. Researchers want to see if ONC201 helps shrink tumors of certain breast or endometrial cancers and if that effect is maintained.
Read more
Objective:
To see if ONC201 shrinks tumors with a lasting effect.
Eligibility:
Adults ages 18 and older who have metastatic breast cancer (hormone-positive or triple-negative) or metastatic endometrial cancers.
Design:
Participants will be screened with:
- Medical history
- Physical exam
- Heart, blood, and urine tests
- Computed tomography (CT) and bone scans
- Review of medical report and tumor sample
- Participants will have a tumor biopsy before starting treatment and after 5 weeks taking the study drug. A scan or ultrasound may be used to guide the biopsy. Patients will receive local anesthetic and a needle will remove a small piece of tumor.
- The study will be done in 28-day cycles. Every day 1 of each cycle participants will repeat most screening tests, will be seen by the physician and receive a supply of the study drug.
- Participants will take the study drug by mouth once every 7 days. They will keep a diary of when they take the drug and any side effects. During cycle 1, participants will get weekly calls to discuss their health and symptoms. Images will be repeated every 2 cycles to evaluate response to the treatment.
Read the detailed description
Background:
- Advanced breast cancer and endometrial cancer have limited treatment options. Current treatments provide a modest improvement in progression free survival, but no treatments improve survival.
- ONC201 is the founding member of a novel class of anticancer drugs called imipridones. The exact mechanism of ONC201 is unknown at this time, but preclinical data suggests that it causes global downregulation of mitochondrial genes leading to mitochondrial damage and ultimately non-apoptotic cell death.
- Preclinical studies have demonstrated that ONC201 selectively kills various cancer cells, including breast cancer cells (hormone-receptor positive cell lines, human epidermal growth factor receptor 2 (HER2+) cell line as well as triple negative breast cancer cell lines) and endometrial cancer cells, while having little effect on normal cells.
- An on-going phase I study of ONC201 has demonstrated clinical benefit in some solid tumors, including endometrial cancer.
Objectives:
- Cohort 1: To determine the progression free survival (PFS) at 8 months of ONC201 in metastatic hormone receptor positive breast cancer (HR+BC)
- Cohort 2: To determine the overall response rate (ORR) of ONC201 in metastatic triple negative breast cancer (TNBC)
- Cohort 3: To determine the overall response rate (ORR) of ONC201 in advanced endometrial cancer (EC)
Eligibility:
Selected Inclusion Criteria
- Histologically confirmed metastatic breast cancer or endometrial cancer with appropriate immunohistochemistry (IHC) testing and confirmation of HER2 non-amplification required for the breast cancer cohorts (cohorts 1 and 2)
- Age 18 years or older
- Female and male breast cancer patients are eligible for the breast cancer cohorts
- Eastern Cooperative Oncology Group (ECOG) 0 or 1
- Measurable metastatic disease with greater than or equal to 1 biopsiable lesion with willingness to undergo a biopsy
- Cohort 1 Hormone receptor + breast cancer (HR+BC) requires prior treatment with greater than or equal to 2 lines of hormonal treatment. No prior treatment required for cohorts 2/3 (TNBC and EC).
- Adequate hematopoietic, hepatic and renal function
Selected Exclusion Criteria
- Patients who have received chemotherapy in the previous 3 weeks (6 weeks for nitrosoureas or mitomycin); other investigational agents within 3 weeks or a programmed cell death protein 1 (PD1)/programmed death-ligand 1 (PDL1) agent within 4 weeks prior to first dose of study treatment.
- Radiotherapy less than or equal to 4 weeks before first dose of study treatment.
- Symptomatic central nervous system (CNS) metastases. Asymptomatic or brain metastases treated greater than 4 weeks from first dose of study treatment are allowed.
- History of invasive malignancy less than or equal to 3 years
- Known history of cardiac arrhythmias including uncontrolled atrial fibrillation, tachyarrhythmias or bradycardia.
- History of congestive heart failure (CHF), or myocardial infarction (MI) or stroke in the previous 3 months will be excluded.
- Started denosumab or bisphosphonate therapy within 28 days prior to Cycle 1 Day 1
- Human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C infection
Design:
- This is a phase II single arm study of ONC201 divided in three cohorts, each cohort with different type of metastatic, advanced disease:
- Cohort 1: HR+ breast cancer (male and female)
- Cohort 2: Triple negative breast cancer (male and female)
- Cohort 3: Endometrial cancer (female only)
- All patients will receive ONC201 at the recommended phase 2 dose (RP2D) of 625mg by mouth every 7 days with each cycle being 28 days long. Patients will receive ONC201 as long as they derive clinical benefit or toxicity becomes impeditive
- Patients will be evaluated for toxicity every 4 weeks by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 and for response every two cycles (8 weeks) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
- Conditions
- Triple Negative Breast Cancer, Endometrial Cancer, Hormone Receptor Positive, HER2 Negative Breast Cancer
- Being tested
- ONC201
- Keywords
- Imipridones, TNBC, Metastatic, Male Breast Cancer
- Medical subject headings
- Triple Negative Breast Neoplasms, Endometrial Neoplasms, Neoplasm Metastasis, Breast Neoplasms, Male
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ONC201Drug
625 mg by mouth every 7 days; each cycle = 28 days. Patients will receive ONC201 as long as they derive clinical benefit or toxicity becomes impeditive.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1-ONC201 in Recurrent/Refractory Metastatic Breast Cancer and Advanced Endometrial Carcinoma | Experimental | Single arm divided in three cohorts, each cohort with a different type of metastatic disease: estrogen receptor (ER) + breast cancer, triple negative breast cancer, and endometrial cancer Receives: Drug: ONC201 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cohort 1 - Progression-free Survival (PFS)
PFS in participants with refractory, metastatic hormone receptor positive breast cancer. PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Progression is at least a 20% increase in the sum of the diameters of target lesions. And the appearance of one or more new lesions.
Measured: Every 8 weeks, while on the Trial. Participants were followed for an average of 8-10 weeks (up to 16 weeks).
Cohort 2 - Overall Response Rate (ORR) (Complete Response (CR) + Partial Response (PR) by the Response Evaluation Criteria in Solid Tumors (RECIST)
Overall response (Complete response (CR) + Partial Response (PR) of ONC201 in participants with metastatic triple negative breast cancer was measured by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is disappearance of all target lesions. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions.
Measured: Every 8 weeks, while on the Trial. Participants were followed for an average of 8-10 weeks (up to 16 weeks).
Cohort 3 - Overall Response Rate (ORR) (Complete Response (CR) + Partial Response (PR) by the Response Evaluation Criteria in Solid Tumors (RECIST)
Overall response (Complete response (CR) + Partial Response (PR) of ONC201 in participants with advanced or metastatic endometrial cancer was measured by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is disappearance of all target lesions. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions.
Measured: Every 8 weeks, while on the Trial. Participants were followed for an average of 8-10 weeks (up to 16 weeks).
Secondary outcomes (4)
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3
Serious and non-serious adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, , Grade 4 is life-threatening, and Grade 5 is death related to adverse event.
Measured: Date treatment consent signed to date off study, approximately 13 months and 28 days for cohort 1, 11 months and 12 days for cohort 2, and 34 months and 29 days for cohort 3.
Cohort 1 - Overall Response Rate (Complete Response (CR) + Partial Response (PR) by the Response Evaluation Criteria in Solid Tumors (RECIST)
Overall response (Complete response (CR) + Partial Response (PR) of ONC201 in participants with refractory, metastatic hormone receptor positive breast cancer was measured by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is disappearance of all target lesions. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions.
Measured: Every 8 weeks, while on the Trial. Participants were followed for an average of 8-10 weeks (up to 16 weeks).
Number of Participants in Cohorts 1, 2, and 3 With Clinical Benefit
Clinical benefit is Complete Response (CR) + Partial Response (PR) + Stable Disease (SD) measured by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is disappearance of all target lesions. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (i.e., at least a 20% increase in the sum of the diameters of target lesions).
Measured: Every 8 weeks, while on the Trial. Participants were followed for an average of 8-10 weeks (up to 16 weeks).
Cohorts 2 and 3 - Progression-free Survival (PFS)
PFS in participants with triple negative breast cancer and endometrial cancer. PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Progression is at least a 20% increase in the sum of the diameters of target lesions. And the appearance of one or more new lesions.
Measured: Every 8 weeks, while on treatment, up to 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2018
- Study start17 Jan 2018
- Primary completion18 Mar 2021
- Study completion7 Oct 2021
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.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Triple Negative Breast CancerStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Stanley Lipkowitz, MD, PhD, National Cancer Institute (NCI)
- Investigators
- Stanley Lipkowitz, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03394027
- Sponsor's protocol ID
- 180034
- Other IDs
- 18-C-0034
- Status last verified
- Jul 2022
- First submitted
- 5 Jan 2018
- Last updated
- 23 Aug 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing data will be shared with subscribers to database of Genotypes and Phenotypes (dbGaP).
Publications
Greer YE, Lipkowitz S. TIC10/ONC201: a bend in the road to clinical development. Oncoscience. 2015 Feb 20;2(2):75-6. doi: 10.18632/oncoscience.133. eCollection 2015. No abstract available.
PubMed 25859547Endo Greer Y, Lipkowitz S. ONC201: Stressing tumors to death. Sci Signal. 2016 Feb 16;9(415):fs1. doi: 10.1126/scisignal.aad7955.
PubMed 26884598Stein MN, Bertino JR, Kaufman HL, Mayer T, Moss R, Silk A, Chan N, Malhotra J, Rodriguez L, Aisner J, Aiken RD, Haffty BG, DiPaola RS, Saunders T, Zloza A, Damare S, Beckett Y, Yu B, Najmi S, Gabel C, Dickerson S, Zheng L, El-Deiry WS, Allen JE, Stogniew M, Oster W, Mehnert JM. First-in-Human Clinical Trial of Oral ONC201 in Patients with Refractory Solid Tumors. Clin Cancer Res. 2017 Aug 1;23(15):4163-4169. doi: 10.1158/1078-0432.CCR-16-2658. Epub 2017 Mar 22.
PubMed 28331050Atkins SLP, Greer YE, Jenkins S, Gatti-Mays ME, Houston N, Lee S, Lee MJ, Rastogi S, Sato N, Burks C, Annunziata CM, Lee JM, Nagashima K, Trepel JB, Lipkowitz S, Zimmer AS. A Single-Arm, Open-Label Phase II Study of ONC201 in Recurrent/Refractory Metastatic Breast Cancer and Advanced Endometrial Carcinoma. Oncologist. 2023 Oct 3;28(10):919-e972. doi: 10.1093/oncolo/oyad164.
PubMed 37279797
Study at a glance
From the registry record, last updated by the sponsor on 23 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of ONC201 in Recurrent/Refractory Metastatic Breast Cancer and Advanced Endometrial Carcinoma
- ClinicalTrials.gov ID
- NCT03394027
- Acronym / sponsor ID
- 180034
- Conditions
- Triple Negative Breast Cancer, Endometrial Cancer, Hormone Receptor Positive, HER2 Negative Breast Cancer
- Keywords
- Imipridones, TNBC, Metastatic, Male Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 17 Jan 2018 (actual)
- Primary completion
- 18 Mar 2021 (actual)
- Study completion
- 7 Oct 2021 (actual)
- First posted
- 9 Jan 2018 (actual)
- Results
- Posted 12 Jan 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
The new drug ONC201 have been shown to kill breast cancer and endometrial cancer cells in the laboratory. The exact mechanism of action is not completely clear yet, but the ONC201 destroys the mitochondria inside the cells. Blocking mitochondrial activity may kill tumor cells, which would shrink tumors. Researchers want to see if ONC201 helps shrink tumors of certain breast or endometrial cancers and if that effect is maintained.
Objective:
To see if ONC201 shrinks tumors with a lasting effect.
Eligibility:
Adults ages 18 and older who have metastatic breast cancer (hormone-positive or triple-negative) or metastatic endometrial cancers.
Design:
Participants will be screened with:
- Medical history
- Physical exam
- Heart, blood, and urine tests
- Computed tomography (CT) and bone scans
- Review of medical report and tumor sample
- Participants will have a tumor biopsy before starting treatment and after 5 weeks taking the study drug. A scan or ultrasound may be used to guide the biopsy. Patients will receive local anesthetic and a needle will remove a small piece of tumor.
- The study will be done in 28-day cycles. Every day 1 of each cycle participants will repeat most screening tests, will be seen by the physician and receive a supply of the study drug.
- Participants will take the study drug by mouth once every 7 days. They will keep a diary of when they take the drug and any side effects. During cycle 1, participants will get weekly calls to discuss their health and symptoms. Images will be repeated every 2 cycles to evaluate response to the treatment.
Detailed description
Background:
- Advanced breast cancer and endometrial cancer have limited treatment options. Current treatments provide a modest improvement in progression free survival, but no treatments improve survival.
- ONC201 is the founding member of a novel class of anticancer drugs called imipridones. The exact mechanism of ONC201 is unknown at this time, but preclinical data suggests that it causes global downregulation of mitochondrial genes leading to mitochondrial damage and ultimately non-apoptotic cell death.
- Preclinical studies have demonstrated that ONC201 selectively kills various cancer cells, including breast cancer cells (hormone-receptor positive cell lines, human epidermal growth factor receptor 2 (HER2+) cell line as well as triple negative breast cancer cell lines) and endometrial cancer cells, while having little effect on normal cells.
- An on-going phase I study of ONC201 has demonstrated clinical benefit in some solid tumors, including endometrial cancer.
Objectives:
- Cohort 1: To determine the progression free survival (PFS) at 8 months of ONC201 in metastatic hormone receptor positive breast cancer (HR+BC)
- Cohort 2: To determine the overall response rate (ORR) of ONC201 in metastatic triple negative breast cancer (TNBC)
- Cohort 3: To determine the overall response rate (ORR) of ONC201 in advanced endometrial cancer (EC)
Eligibility:
Selected Inclusion Criteria
- Histologically confirmed metastatic breast cancer or endometrial cancer with appropriate immunohistochemistry (IHC) testing and confirmation of HER2 non-amplification required for the breast cancer cohorts (cohorts 1 and 2)
- Age 18 years or older
- Female and male breast cancer patients are eligible for the breast cancer cohorts
- Eastern Cooperative Oncology Group (ECOG) 0 or 1
- Measurable metastatic disease with greater than or equal to 1 biopsiable lesion with willingness to undergo a biopsy
- Cohort 1 Hormone receptor + breast cancer (HR+BC) requires prior treatment with greater than or equal to 2 lines of hormonal treatment. No prior treatment required for cohorts 2/3 (TNBC and EC).
- Adequate hematopoietic, hepatic and renal function
Selected Exclusion Criteria
- Patients who have received chemotherapy in the previous 3 weeks (6 weeks for nitrosoureas or mitomycin); other investigational agents within 3 weeks or a programmed cell death protein 1 (PD1)/programmed death-ligand 1 (PDL1) agent within 4 weeks prior to first dose of study treatment.
- Radiotherapy less than or equal to 4 weeks before first dose of study treatment.
- Symptomatic central nervous system (CNS) metastases. Asymptomatic or brain metastases treated greater than 4 weeks from first dose of study treatment are allowed.
- History of invasive malignancy less than or equal to 3 years
- Known history of cardiac arrhythmias including uncontrolled atrial fibrillation, tachyarrhythmias or bradycardia.
- History of congestive heart failure (CHF), or myocardial infarction (MI) or stroke in the previous 3 months will be excluded.
- Started denosumab or bisphosphonate therapy within 28 days prior to Cycle 1 Day 1
- Human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C infection
Design:
- This is a phase II single arm study of ONC201 divided in three cohorts, each cohort with different type of metastatic, advanced disease:
- Cohort 1: HR+ breast cancer (male and female)
- Cohort 2: Triple negative breast cancer (male and female)
- Cohort 3: Endometrial cancer (female only)
- All patients will receive ONC201 at the recommended phase 2 dose (RP2D) of 625mg by mouth every 7 days with each cycle being 28 days long. Patients will receive ONC201 as long as they derive clinical benefit or toxicity becomes impeditive
- Patients will be evaluated for toxicity every 4 weeks by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 and for response every two cycles (8 weeks) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm 1-ONC201 in Recurrent/Refractory Metastatic Breast Cancer and Advanced Endometrial Carcinoma | Experimental | Drug: ONC201Single arm divided in three cohorts, each cohort with a different type of metastatic disease: estrogen receptor (ER) + breast cancer, triple negative breast cancer, and endometrial cancer |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients must have histologically or cytologically confirmed persistent or recurrent advanced or metastatic invasive endometrial cancer (EC) for which standard curative measures do not exist or are no longer effective.
- Patients must have measurable disease, per RECIST 1.1
- Patients must have at least one lesion deemed safe to biopsy and be willing to undergo mandatory biopsies.
- Women with endometrial cancer must have had at least one prior line of therapy in the metastatic/recurrent setting but there is no limit to the number of prior chemotherapy lines. Patients are eligible if they have received treatment with immunotherapy, such PD-1 inhibitors, PD-L1 inhibitors or CTLA4 inhibitors.
- Age greater than or equal to 18 years.
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| ONC201625 mg by mouth every 7 days; each cycle = 28 days. Patients will receive ONC201 as long as they derive clinical benefit or toxicity becomes impeditive. | Drug | Arm 1-ONC201 in Recurrent/Refractory Metastatic Breast Cancer and Advanced Endometrial Carcinoma |
Primary outcome
Cohort 1 - Progression-free Survival (PFS)
Time frame: Every 8 weeks, while on the Trial. Participants were followed for an average of 8-10 weeks (up to 16 weeks).
PFS in participants with refractory, metastatic hormone receptor positive breast cancer. PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Progression is at least a 20% increase in the sum of the diameters of target lesions. And the appearance of one or more new lesions.
Cohort 2 - Overall Response Rate (ORR) (Complete Response (CR) + Partial Response (PR) by the Response Evaluation Criteria in Solid Tumors (RECIST)
Time frame: Every 8 weeks, while on the Trial. Participants were followed for an average of 8-10 weeks (up to 16 weeks).
Overall response (Complete response (CR) + Partial Response (PR) of ONC201 in participants with metastatic triple negative breast cancer was measured by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is disappearance of all target lesions. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions.
Cohort 3 - Overall Response Rate (ORR) (Complete Response (CR) + Partial Response (PR) by the Response Evaluation Criteria in Solid Tumors (RECIST)
Time frame: Every 8 weeks, while on the Trial. Participants were followed for an average of 8-10 weeks (up to 16 weeks).
Overall response (Complete response (CR) + Partial Response (PR) of ONC201 in participants with advanced or metastatic endometrial cancer was measured by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is disappearance of all target lesions. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions.
4 secondary outcomes
Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3
Time frame: Date treatment consent signed to date off study, approximately 13 months and 28 days for cohort 1, 11 months and 12 days for cohort 2, and 34 months and 29 days for cohort 3.
Cohort 1 - Overall Response Rate (Complete Response (CR) + Partial Response (PR) by the Response Evaluation Criteria in Solid Tumors (RECIST)
Time frame: Every 8 weeks, while on the Trial. Participants were followed for an average of 8-10 weeks (up to 16 weeks).
Number of Participants in Cohorts 1, 2, and 3 With Clinical Benefit
Time frame: Every 8 weeks, while on the Trial. Participants were followed for an average of 8-10 weeks (up to 16 weeks).
Cohorts 2 and 3 - Progression-free Survival (PFS)
Time frame: Every 8 weeks, while on treatment, up to 3 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Aug 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 25859547Greer YE, Lipkowitz S. TIC10/ONC201: a bend in the road to clinical development. Oncoscience. 2015 Feb 20;2(2):75-6. doi: 10.18632/oncoscience.133. eCollection 2015. No abstract available.
- Background: PubMed 26884598Endo Greer Y, Lipkowitz S. ONC201: Stressing tumors to death. Sci Signal. 2016 Feb 16;9(415):fs1. doi: 10.1126/scisignal.aad7955.
- Background: PubMed 28331050Stein MN, Bertino JR, Kaufman HL, Mayer T, Moss R, Silk A, Chan N, Malhotra J, Rodriguez L, Aisner J, Aiken RD, Haffty BG, DiPaola RS, Saunders T, Zloza A, Damare S, Beckett Y, Yu B, Najmi S, Gabel C, Dickerson S, Zheng L, El-Deiry WS, Allen JE, Stogniew M, Oster W, Mehnert JM. First-in-Human Clinical Trial of Oral ONC201 in Patients with Refractory Solid Tumors. Clin Cancer Res. 2017 Aug 1;23(15):4163-4169. doi: 10.1158/1078-0432.CCR-16-2658. Epub 2017 Mar 22.
- Derived from this study: PubMed 37279797Atkins SLP, Greer YE, Jenkins S, Gatti-Mays ME, Houston N, Lee S, Lee MJ, Rastogi S, Sato N, Burks C, Annunziata CM, Lee JM, Nagashima K, Trepel JB, Lipkowitz S, Zimmer AS. A Single-Arm, Open-Label Phase II Study of ONC201 in Recurrent/Refractory Metastatic Breast Cancer and Advanced Endometrial Carcinoma. Oncologist. 2023 Oct 3;28(10):919-e972. doi: 10.1093/oncolo/oyad164.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing data will be shared with subscribers to database of Genotypes and Phenotypes (dbGaP).
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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.
Stanley Lipkowitz, M.D. principal investigator
National Cancer Institute (NCI)
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 Triple Negative Breast Cancer and Endometrial Cancer, run by National Cancer Institute (NCI) 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 8 inclusion and 0 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 23 Aug 2022. 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 12 Jan 2022). 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?
Cohort 1 - Progression-free Survival (PFS) (time frame: Every 8 weeks, while on the Trial. Participants were followed for an average of 8-10 weeks (up to 16 weeks).). The study lists 3 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 NCT03394027, which also lists 4 linked publications.
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 23 Aug 2022; AzTrials last refreshed its copy on 26 Oct 2026.