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Trial record 51 of 211 for:    Oral Cancer | Recruiting Studies | NIH

ONC201 in Recurrent/Refractory Metastatic Breast Cancer and Advanced Endometrial Carcinoma

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ClinicalTrials.gov Identifier: NCT03394027
Recruitment Status : Recruiting
First Posted : January 9, 2018
Last Update Posted : December 5, 2018
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief 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:

<TAB>Medical history

<TAB>Physical exam

<TAB>Heart, blood, and urine tests

<TAB>CT and bone scans

<TAB>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 reponse to the treatment.


Condition or disease Intervention/treatment Phase
Triple Negative Breast Cancer Endometrial Cancer Hormone Receptor Positive, HER2 Negative Breast Cancer Drug: ONC201 Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of ONC201 in Recurrent/Refractory Metastatic Breast Cancer and Advanced Endometrial Carcinoma
Actual Study Start Date : January 17, 2018
Estimated Primary Completion Date : August 1, 2022
Estimated Study Completion Date : December 30, 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Arm 1
Single arm divided in three cohorts, each cohort with a different type of metastatic disease: ER + breast cancer, triple negative breast cancer, and endometrial cancer
Drug: ONC201
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.




Primary Outcome Measures :
  1. Cohort 1 - Progression-free survival (PFS) [ Time Frame: at 8 months ]
    Cohort 1 HR+BC - To determine the progression free survival at 8 months (PFS by RECIST) of ONC201 in patients with refractory, metastic hormone receptor positive breast cancer

  2. Cohort 2 - Overall Response Rate (ORR) [ Time Frame: every 8 weeks ]
    To determine the overall response rate (ORR; CR + PR by RECIST) of ONC201 in patients with metastic triple negative breast cancer

  3. Cohort 3 - Overall Response Rate (ORR) [ Time Frame: every 8 weeks ]
    To determine the ORR of ONC201 in patients with advanced or metastatic endometrial cancer


Secondary Outcome Measures :
  1. Cohorts 1,2, and 3 - tabulation of adverse event type and grade [ Time Frame: every 4 weeks ]
    tabulation of adverse event type and grade every 4-week cycle

  2. Cohort 1 - Overall Response Rate [ Time Frame: every 8 weeks ]
    To determine the overall response rate (ORR; CR + PR by RECIST) of ONC201 in patients with refractory, metastatic hormone receptor positive breast cancer

  3. Cohorts 1,2, and 3 - Clinical Benefit Rate [ Time Frame: every 8 weeks ]
    CR + PR + SD by RECIST

  4. Cohorts 2 and 3 - Progression-free Survival [ Time Frame: every 8 weeks ]
    PFS by RECIST



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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA FOR COHORT 1: HORMONE RECEPTOR POSITIVE BREAST CANCER:
  • Patients must have histologically confirmed persistent or recurrent invasive metastatic hormone receptor positive, 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 greatr 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 ASCO-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 <4.0 signals/cell or b) Dualprobe HER2/CEP17 ratio <2.0 with an average HER2 copy number <4.0 signals/cell)and HER2 testing must have been performed in a laboratory accredited by the College of American Pathologists (CAP) or another accrediting entity.
  • 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.
  • HR+BC patients must have received prior treatment with at least 2 lines of hormonal treatment (SERM, AI, or fulvestrant) and deemed ineligible for further hormonal therapy. Patients may have received prior chemotherapy and there is no limit to the number of prior chemotherapy.
  • Age greater than or equal to18 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 the definition of Gilbert's syndrome prior to entering study.
  • Adequate bone marrow function, defined as absolute neutrophil (ANC) greater than or equal to 1,500/mm^3 (greater than or equal to 1.5 X10^6/L), platelet count greater than or equal to 75,000/mm^3 (greater than or equal to 75 X10^6/L), and hemoglobin greater than or equal to 9 mg/dL (transfusion to obtain hemoglobin greater than or equal to 9 mg/dL within 24 hours prior to dosing is allowed).
  • Patients must be able to swallow oral medications (capsules) without chewing, breaking, crushing, opening or otherwise altering the product formulation.
  • The effects of ONC201 on the developing human fetus are unknown. For this reason and because imipridone agents are known to be teratogenic, female patients must either be of non-reproductive potential (i.e., post-menopausal by history: greater than or equal to 60 years old and no menses for greater than or equal to 1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry and agree to use contraception or abstinence during the study and for and for at least 4 weeks after the final dose of any study-related medications. Male patients must use at least two forms of contraception during the study and for at least 4 weeks after the final dose of any study-related medications or have a partner who is not of reproductive potential.
  • Ability of subject to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA FOR COHORT 1: HORMONE RECEPTOR POSITIVE BREAST CANCER:

  • Patients who have received chemotherapy in the previous 3 weeks (6 weeks for nitrosoureas or mitomycin); other investigational agents within 3 weeks or a PD1/PDL1 agent within 4 weeks prior to first dose of study enrollment.
  • Patients who have undergone radiotherapy within 4 weeks of first dose of study treatment.
  • Patients with a history of another invasive malignancy within the last 3 years.
  • Patients with symptomatic brain metastases or leptomeningeal involvement. Patients with asymptomatic or brain metastases that have been treated with radiation at least 4 weeks prior to first dose of study treatment are allowed.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to imipridones or other agents used in study.
  • Patients with a mean QTcF interval of > 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 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 ER negative (ER < 10%), PR negative (PR <10%). HER2 will be considered negative per ASCO-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 <4.0 signals/cell or b) Dual-probe HER2/CEP17 ratio <2.0 with an average HER2 copy number <4.0 signals/cell) and HER2 testing must have been performed in a laboratory accredited by the College of American Pathologists (CAP) or another accrediting entity.
  • Patients must have received at least one line of prior chemotherapy in the metastatic setting.
  • 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.
  • Eligible patients may or may not have received prior chemotherapy and there is no limit to the number of prior chemotherapy. Patients are also 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 the definition of Gilber's syndrome prior to entering study.
  • Adequate bone marrow function, defined as absolute neutrophil (ANC) greater than or equal to 1,500/mm^3 (greater than or equal to 1.5 X10^6/L), platelet count greater than or equal to 75,000/mm^3 (greater than or equal to 75 X10^6/L), and hemoglobin greater than or equal to 9 mg/dL (transfusion to obtain hemoglobin greater than or equal to 9 mg/dL within 24 hours prior to dosing is allowed)
  • Patients must be able to swallow oral medications (capsules) without chewing, breaking, crushing, opening or otherwise altering the product formulation. The effects of ONC201 on the developing human fetus are unknown. For this reason and because imipridone agents as well as other therapeutic agents used in this trial are known to be teratogenic. Female patients must either be of non-reproductive potential (i.e., post-menopausal by history: greater than or equal to 60 years old and no menses for greater than or equal to 1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry and agree to use contraception or abstinence during the study and for and for at least 4 weeks after the final dose of any study-related medications. Male patients must use at least two forms of contraception during the study and for and for at least 4 weeks after the final dose of any study-related medications or have a partner who is not of reproductive potential.
  • Ability of subject to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA FOR COHORT 2: TRIPLE NEGATIVE BREAST CANCER:

  • Patients who have received chemotherapy in the previous 3 weeks (6 weeks for nitrosoureas or mitomycin); other investigational agents within 3 weeks or a PD1/PDL1 agent within 4 weeks prior to first dose of study treatment.
  • Patients who have undergone radiotherapy within 4 weeks of first dose of study treatment.
  • Patients with a history of another invasive malignancy within the last 3 years.
  • Patients with symptomatic brain metastases or leptomeningeal involvement. Patients with asymptomatic or brain metastases that have been treated with radiation at least 4 weeks prior to first dose of study treatment are allowed.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to imipridones or other agents used in study.
  • Patients with a mean QTcF interval of > 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 because of the potential for pharmacokinetic interactions with ONC201.
  • Patients who have known active Hepatitis B, or Hepatitis C infections.

INCLUSION CRITERIA FOR COHORT 3: ENDOMETRIAL CANCER:

  • 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 the d...

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03394027


Contacts
Contact: Nicole D. Houston, R.N. (240) 760-6127 houstonnd@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    888-624-1937      
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Alexandra S Zimmer, M.D. National Cancer Institute (NCI)

Additional Information:
Publications:
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT03394027     History of Changes
Other Study ID Numbers: 180034
18-C-0034
First Posted: January 9, 2018    Key Record Dates
Last Update Posted: December 5, 2018
Last Verified: November 30, 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Impiridones
TNBC
Metastatic
Male Breast Cancer

Additional relevant MeSH terms:
Breast Neoplasms
Endometrial Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Breast Diseases
Skin Diseases
Uterine Diseases
Genital Diseases, Female