Phase 2
N=30
ONC201 in Recurrent/Refractory Metastatic Breast Cancer and Advanced Endometrial Carcinoma
Triple Negative Breast Cancer · Endometrial Cancer · Hormone Receptor Positive, HER2 Negative Breast Cancer
Bottom Line
View on ClinicalTrials.gov: NCT03394027 ↗Enrolled (actual)
30
Serious AEs
54.6%
Results posted
Jan 2022
Primary outcome: Primary: Cohort 1 - Progression-free Survival (PFS) — 1.9 Months
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- ONC201 (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- National Cancer Institute (NCI)
- Primary completion
- Mar 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Cohort 1 - Progression-free Survival (PFS) |
1.9 | — |
| PRIMARY Cohort 2 - Overall Response Rate (ORR) (Complete Response (CR) + Partial Response (PR) by the Response Evaluation Criteria in Solid Tumors (RECIST) |
0; 0 | — |
| PRIMARY Cohort 3 - Overall Response Rate (ORR) (Complete Response (CR) + Partial Response (PR) by the Response Evaluation Criteria in Solid Tumors (RECIST) |
0; 0 | — |
| SECONDARY Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3 |
0; 0; 0; 0; 0; 1 | — |
| SECONDARY Cohort 1 - Overall Response Rate (Complete Response (CR) + Partial Response (PR) by the Response Evaluation Criteria in Solid Tumors (RECIST) |
0; 0 | — |
| SECONDARY Number of Participants in Cohorts 1, 2, and 3 With Clinical Benefit |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Cohorts 2 and 3 - Progression-free Survival (PFS) |
1.2; 2 | — |
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. 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.
Eligibility Criteria
- INCLUSION CRITERIA FOR COHORT 1: HORMONE RECEPTOR POSITIVE BREAST CANCER:
- Patients must have histologically confirmed persistent or recurrent invasive metastatic hormone receptor positive, human epidermal growth factor receptor 2 (HER2) normal breast cancer for which standard curative measures do not exist or are no longer effective. Hormone receptor positive is defined as estrogen receptor (ER) positive greater than or equal to 10% by immunohistochemistry (IHC) and/or progesterone receptor (PR) positive greater than or equal to 10% by IHC.HER2 will be considered negative per American Society of Clinical Oncology (ASCO)-College of American Pathologists (CAP) guidelines (HER2 test result as negative if a single test (or both tests) performed show: 1) IHC 1+ as defined by incomplete membrane staining that is faint/barely perceptible and within >10% of the invasive tumor cells; 2) IHC 0 as defined by no staining observed or membrane staining that is incomplete and is faint/barely perceptible and within less than or equal to 10% of the invasive tumor cells; or 3) ISH negative based on: a) Single-probe average HER2 copy number 500 msec or receiving therapeutic agents known to prolong the QT interval
- Known history of cardiac arrhythmias including uncontrolled atrial fibrillation, tachyarrhythmias or bradycardia, history of congestive heart failure, or myocardial infarction or stroke in the previous 3 months will be excluded.
- Known history of gastrointestinal illnesses that would preclude the absorption of ONC201, which is an oral agent.
- Patients with bone metastases who have initiated denosumab or bisphosphonate therapy within 28 days prior to Cycle 1 Day 1.
- Pregnant women are excluded from this study because ONC201 has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ONC201, breastfeeding should be discontinued if the mother is treated with ONC201. These potential risks may also apply to other agents used in this study.
- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with ONC201.
- Patients who have known active Hepatitis B, or Hepatitis C infections.
INCLUSION CRITERIA FOR COHORT 2: TRIPLE NEGATIVE BREAST CANCER:
- Patients must have histologically or cytologically confirmed persistent or recurrent invasive, metastatic triple negative breast cancer (TNBC) for which standard curative measures do not exist or are no longer effective. TNBC, defined as estrogen receptor (ER) negative (ER 10% of the invasive tumor cells; 2) IHC 0 as defined by no staining observed or membrane staining that is incomplete and is faint/barely perceptible and within less than or equal to 10% of the invasive tumor cells; or 3) ISH negative based on: a) Single-probe average HER2 copy number 500 msec or receiving therapeutic agents known to prolong the QT interval
- Known history of cardiac arrhythmias including uncontrolled atrial fibrillation, tachyarrhythmias or bradycardia, history of congestive heart failure, or myocardial infarction or stroke in the previous 3 months will be excluded.
- Known history of gastrointestinal illnesses that would preclude the absorption of ONC201, which is an oral agent
- Patients with bone metastases who have initiated denosumab or bisphosphonate therapy within 28 days prior to Cycle 1 Day 1.
- Pregnant women are excluded from this study because ONC201 has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ONC201, breastfeeding should be discontinued if the mother is treated with ONC201. These potential risks may also apply to other agents used in this study.
- HIV-positive patients on combination antiretroviral therapy are ineligible
Data sourced from ClinicalTrials.gov (NCT03394027). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.