ONC201 With a Methionine-Restricted Diet in Patients With Metastatic Triple Negative Breast Cancer

NCT03733119 | Terminated Phase 2 Results DMC FDA Drug

• 6 other identifiers: UW171072018-0252A534260SMPH/MEDICINE/HEM-ONCNCI-2018-01878Protocol Version 02/16/2021
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well Akt/ERK inhibitor ONC201 (ONC201) with a methionine-restricted (MR) diet works in treating participants with triple negative breast cancer that has spread to other places in the body or cannot be removed by surgery. ONC201 activates a process that leads to the death of a cell. ONC201 is able to target tumor cells to get rid of them, but does not affect normal cells. MR diet is a methionine-free amino acid modified medical food. The addition of an intermittent MR diet may enhance the activity of ONC201. Giving ONC201 and an MR diet may work better in treating participants with breast cancer.

Conditions

Triple Negative Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR) - Number of Participants Who Responded to Treatment

  ORR will be estimated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, by dividing the total number of responders (complete plus partial responses plus CR or PR) or (CR or PR), respectively, by number of subjects with measurable disease and the exact 95% confidence interval will be provided. Due to early termination with few participants, only the counts of events have been reported.

  maximum follow up time was 1 year

Secondary Outcomes (5)

• Progression-free Survival (PFS) - Number of Participants With PFS

  maximum follow up time was 1 year

• Overall Survival (OS) - Number of Participants Who Survived the Study Period

  maximum follow up time was 1 year

• Clinical Benefit Rate (CBR) - Number of Participants Who Experienced Clinical Benefit

  At 4 months

• Duration of Response (DOR)

  Up to 2 years

• Incidence of Adverse Events - Number of Participants Who Experienced Adverse Events

  30 days after last dose of study drug, up to 4 months on study

Other Outcomes (2)

• Time to Development or Worsening of Brain Metastases

  Up to 2 years

• Number of Participants With Developing or Worsening Brain Metastasis

  up to 4 months

Study Arms (2)

Akt/ERK inhibitor ONC201

EXPERIMENTAL

Participants receive Akt/ERK inhibitor ONC201 PO on days 3, 10, and 17. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: Akt/ERK Inhibitor ONC201

Akt/ERK inhibitor ONC201, methionine-restricted diet

EXPERIMENTAL

Participants receive Akt/ERK inhibitor ONC201 PO on days 3, 10, and 17. Participants also receive methionine-restricted diet PO on days 1-5, 8-12, and 15-19. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: Akt/ERK Inhibitor ONC201; Dietary Supplement: Methionine-Restricted Diet

Interventions

Akt/ERK Inhibitor ONC201 DRUG

Given PO

Also known as: ONC201, TIC10

Akt/ERK inhibitor ONC201; Akt/ERK inhibitor ONC201, methionine-restricted diet

Methionine-Restricted Diet DIETARY_SUPPLEMENT

Given PO

Akt/ERK inhibitor ONC201, methionine-restricted diet

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Metastatic or unresectable TNBC (estrogen receptor \[ER\] \< 10%, progesterone receptor \[PR\] \< 10% and HER2 negative either by immunohistochemistry \[IHC\] or in situ hybridization method by American Society of Clinical Oncology \[ASCO\]-College of American Pathologists \[CAP\] guidelines). For patients with a previous tumor sample with positive ER, PR and/or HER2 results, if the most recent biopsy meets study criteria, they will be eligible.
• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. within 28 days prior to registration
• Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately
• Any number of prior lines of systemic therapy for metastatic disease
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
• Prior cancer treatment, including radiotherapy, must be completed at least 14 days prior to registration and the subject must have recovered from all reversible acute toxic effects of the regimen to =\< grade 1 or to baseline prior to initiation of that therapy. Grade 2 or higher exceptions include alopecia, up to grade 2 neuropathy, and other grade 2 AEs or lab values not constituting a safety risk in the opinion of the treating physician. This criteria does not apply to lab tests for normal organ and marrow function outlined below.
• No active central nervous system (CNS) metastatic disease; subjects with prior definitive treatment of their CNS disease by surgical resection, stereotactic body radiation therapy (SBRT) or whole-brain radiotherapy (WBRT) \> 28 days ago will be eligible if asymptomatic and off systemic steroids
• Life expectancy of greater than 12 weeks
• Normal organ and marrow function as defined per protocol definitions
• Absolute neutrophil count (ANC) \> 1.5 x 10\^3/uL
• Platelet count \>= 100 x 10\^3/uL
• Hemoglobin \>= 9 g/dL
• Total bilirubin \< 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) ≤ 2.5 x ULN if participant has liver metastases, ≤5x ULN.
• Creatinine \< ULN (institutional normal)

You may not qualify if:

• No prior therapy with TRAIL receptor agonists
• Active infection requiring systemic therapy. Patients with a known history of human immunodeficiency virus (HIV) must have a CD4 count \>= the institutional lower limit of normal within 28 days prior to registration. Patients with HIV must also be on a stable antiretroviral regimen for \>= 28 days before registration
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study)
• Known additional malignancy that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, or other cancer for which the subject has been disease-free for at least three years
• Treatment with any investigational drug agent =\< 14 days prior to registration or within 5 half-lives of that investigational product, whichever is longer
• Participant who has had major surgery =\< 14 days prior to registration or has not recovered from major side effects of the surgery (tumor biopsy is not considered as major surgery)
• Known hypersensitivity to any of the excipients of ONC201
• Any impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
• Any concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, cause unacceptable safety risks, contraindicate subject participation in the clinical study or compromise compliance with the protocol (e.g. chronic pancreatitis, chronic active hepatitis, active untreated or uncontrolled fungal, bacterial or viral infections, etc.)
• Participants who follow a vegan or vegetarian diet

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• The V Foundation for Cancer Research: collaborator

Study Sites (1)

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

Location

Related Publications (1)

• Liao M, Qin R, Huang W, Zhu HP, Peng F, Han B, Liu B. Targeting regulated cell death (RCD) with small-molecule compounds in triple-negative breast cancer: a revisited perspective from molecular mechanisms to targeted therapies. J Hematol Oncol. 2022 Apr 12;15(1):44. doi: 10.1186/s13045-022-01260-0.

  PMID: 35414025 DERIVED

Related Links

• University of Wisconsin Carbone Cancer Center

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

TIC10 compound

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Limitations and Caveats

Trial was terminated early due to slow accrual, not powered for meaningful results, statistical analysis not completed.

Results Point of Contact

• Title: Kari Wisinski, MD
• Organization: University of Wisconsin Carbone Cancer Center

kbwisinski@medicine.wisc.edu

608-262-2876

Study Officials

• Kari Wisinski, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2018
• First Posted: November 7, 2018
• Study Start: November 13, 2018
• Primary Completion: February 13, 2021
• Study Completion: February 13, 2021
• Last Updated: March 10, 2022
• Results First Posted: March 10, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)