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

• Sponsor: University of Wisconsin, Madison (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03733119
• Collaborator: The V Foundation for Cancer Research (Other)
• Enrollment: 4
• Location: 1
• Arms: 2
• Actual Duration (Months): 27
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Triple Negative Breast Cancer	Drug: Akt/ERK Inhibitor ONC201; Dietary Supplement: Methionine-Restricted Diet	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To determine objective response rate (ORR) to ONC201 with a methionine-restricted diet in patients with metastatic triple negative breast cancer (TNBC).

SECONDARY OBJECTIVES:

1. To determine progression-free survival (PFS) to ONC201 with a methionine-restricted diet in patients with metastatic TNBC.

2. To determine clinical benefit rate (complete or partial response plus stable disease) (CBR) at 4 months to ONC201 with a methionine-restricted diet in patients with metastatic TNBC.

3. To determine overall survival (OS) to ONC201 with a methionine-restricted diet in patients with metastatic TNBC.

4. To assess metabolic indices in patients with metastatic TNBC treated with ONC201 and a methionine-restricted diet.

5. To assess the expression of TRAIL receptor in circulating tumor cells (CTCs) prior, during and upon progression in patients with metastatic TNBC treated with ONC201 with a methionine-restricted diet.

EXPLORATORY OBJECTIVES:

1. To determine time to development of brain metastases or worsening of brain metastases in patients with metastatic TNBC treated with ONC201 with a methionine-restricted diet.

STUDY DESIGN Patients with metastatic TNBC will be enrolled in a single-arm study evaluating ONC201 with a methionine-restricted diet.

After completion of study treatment, participants are followed up every 3 months for 2 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 4 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: ONC201 With a Methionine-Restricted Diet in Patients With Metastatic Triple Negative Breast Cancer
• Actual Study Start Date: Nov 13, 2018
• Actual Primary Completion Date: Feb 13, 2021
• Actual Study Completion Date: Feb 13, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Akt/ERK inhibitor ONC201 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; Given PO; Other Names: ONC201 TIC10
Experimental: Akt/ERK inhibitor ONC201, methionine-restricted diet 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; Given PO; Other Names: ONC201 TIC10 ; Dietary Supplement: Methionine-Restricted Diet; Given PO

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate (ORR) - Number of Participants Who Responded to Treatment [maximum follow up time was 1 year]

   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.

Secondary Outcome Measures

1. Progression-free Survival (PFS) - Number of Participants With PFS [maximum follow up time was 1 year]

   Will be summarized using Kaplan-Meier estimates of the median survival times. Point estimates as well as 95% confidence intervals will be provided. Due to early termination with few participants, only the counts of events have been reported.

2. Overall Survival (OS) - Number of Participants Who Survived the Study Period [maximum follow up time was 1 year]

   Will be summarized using Kaplan-Meier estimates of the median survival times. Point estimates as well as 95% confidence intervals will be provided. Due to early termination with few participants, only the counts of events have been reported.

3. Clinical Benefit Rate (CBR) - Number of Participants Who Experienced Clinical Benefit [At 4 months]

   CBR will be estimated according to RECIST 1.1, by dividing the total number of responders (complete plus partial responses plus CR or PR or stable disease [SD]), 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.

4. Duration of Response (DOR) [Up to 2 years]

   Will be measured using Kaplan-Meier methodology. A 95% confidence interval will be provided for the median duration of response.

5. 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]

   Incidence of adverse events as measured by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 5.0. Safety and tolerability will be assessed by frequency tables. Also, metabolic indices in patients with metastatic triple negative breast cancer (TNBC) treated with ONC-201 and a methionine-restricted diet will be assessed by frequency tables and descriptive statistics.

Other Outcome Measures

1. Time to Development or Worsening of Brain Metastases [Up to 2 years]

   Will be summarized using Kaplan-Meier methodology.

2. Number of Participants With Developing or Worsening Brain Metastasis [up to 4 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 74 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 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)

• Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to registration. NOTE: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy), or they are naturally postmenopausal for at least 12 consecutive months

• Females of childbearing potential must be willing to abstain from heterosexual activity or must agree to use adequate contraception (hormonal or barrier method) for the duration of study participation and for 90 days after discontinuation of study treatment

• Ability of the subject to understand and comply with study procedures for the entire length of the study

• Able to swallow ONC201

• Be willing to discontinue vitamin and mineral supplements for the duration of the study if randomized to receive the methionine restricted diet

Exclusion Criteria:

• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin	United States	53792

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Kari Wisinski, MD, University of Wisconsin, Madison

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 16, 2021

More Information

Additional Information:

• University of Wisconsin Carbone Cancer Center

Publications

None provided.

• Responsible Party: University of Wisconsin, Madison
• ClinicalTrials.gov Identifier: NCT03733119
• Other Study ID Numbers: UW17107; 2018-0252; A534260; SMPH/MEDICINE/HEM-ONC; NCI-2018-01878; Protocol Version 02/16/2021
• First Posted: Nov 7, 2018
• Last Update Posted: Mar 10, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Breast Neoplasms; Triple Negative Breast Neoplasms; TIC10 compound

Study Results

Participant Flow

Pre-assignment Detail	4 participants enrolled, 1 determined not to meet the eligibility criteria, 3 participants started treatment

Arm/Group Title	Akt/ERK Inhibitor ONC201	Akt/ERK Inhibitor ONC201, Methionine-restricted Diet
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	2	2
Treated	2	1
Stopped Treatment After 1 Dose	1	0
Stopped Treatment After 3 Cycles	1	1
COMPLETED	0	0
NOT COMPLETED	2	2

Baseline Characteristics

Arm/Group Title	Akt/ERK Inhibitor ONC201	Akt/ERK Inhibitor ONC201, Methionine-restricted Diet	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	2	2	4
Age, Customized (Count of Participants)
20-29	0 0%	1 50%	1 25%
30-39	0 0%	0 0%	0 0%
40-49	1 50%	0 0%	1 25%
50-59	1 50%	0 0%	1 25%
60-69	0 0%	1 50%	1 25%
Sex: Female, Male (Count of Participants)
Female	2 100%	2 100%	4 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	2 100%	2 100%	4 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	2 100%	2 100%	4 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	2 100%	2 100%	4 100%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate (ORR) - Number of Participants Who Responded to Treatment
Description	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.
Time Frame	maximum follow up time was 1 year

Outcome Measure Data

Analysis Population Description

study was terminated early, data for response rate at 2 years per protocol was not collected

Arm/Group Title	Akt/ERK Inhibitor ONC201	Akt/ERK Inhibitor ONC201, Methionine-restricted Diet
Arm/Group Description	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.	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.
Measure Participants	2	1
Count of Participants [Participants]	0 0%	0 0%

2. Secondary Outcome

Title	Progression-free Survival (PFS) - Number of Participants With PFS
Description	Will be summarized using Kaplan-Meier estimates of the median survival times. Point estimates as well as 95% confidence intervals will be provided. Due to early termination with few participants, only the counts of events have been reported.
Time Frame	maximum follow up time was 1 year

Outcome Measure Data

Analysis Population Description

study was terminated early, data for progression free survival at 2 years not collected

Arm/Group Title	Akt/ERK Inhibitor ONC201	Akt/ERK Inhibitor ONC201, Methionine-restricted Diet
Arm/Group Description	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.	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.
Measure Participants	2	1
Count of Participants [Participants]	0 0%	0 0%

3. Secondary Outcome

Title	Overall Survival (OS) - Number of Participants Who Survived the Study Period
Description	Will be summarized using Kaplan-Meier estimates of the median survival times. Point estimates as well as 95% confidence intervals will be provided. Due to early termination with few participants, only the counts of events have been reported.
Time Frame	maximum follow up time was 1 year

Outcome Measure Data

Analysis Population Description

study was terminated early, data for overall survival at 2 years not collected

Arm/Group Title	Akt/ERK Inhibitor ONC201	Akt/ERK Inhibitor ONC201, Methionine-restricted Diet
Arm/Group Description	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.	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.
Measure Participants	2	1
Count of Participants [Participants]	0 0%	0 0%

4. Secondary Outcome

Title	Clinical Benefit Rate (CBR) - Number of Participants Who Experienced Clinical Benefit
Description	CBR will be estimated according to RECIST 1.1, by dividing the total number of responders (complete plus partial responses plus CR or PR or stable disease [SD]), 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.
Time Frame	At 4 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Akt/ERK Inhibitor ONC201	Akt/ERK Inhibitor ONC201, Methionine-restricted Diet
Arm/Group Description	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.	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.
Measure Participants	2	1
Count of Participants [Participants]	0 0%	0 0%

5. Secondary Outcome

Title	Duration of Response (DOR)
Description	Will be measured using Kaplan-Meier methodology. A 95% confidence interval will be provided for the median duration of response.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

duration of response could not be calculated as there were no responders on study

Arm/Group Title	Akt/ERK Inhibitor ONC201	Akt/ERK Inhibitor ONC201, Methionine-restricted Diet
Arm/Group Description	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.	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.
Measure Participants	0	0

6. Secondary Outcome

Title	Incidence of Adverse Events - Number of Participants Who Experienced Adverse Events
Description	Incidence of adverse events as measured by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 5.0. Safety and tolerability will be assessed by frequency tables. Also, metabolic indices in patients with metastatic triple negative breast cancer (TNBC) treated with ONC-201 and a methionine-restricted diet will be assessed by frequency tables and descriptive statistics.
Time Frame	30 days after last dose of study drug, up to 4 months on study

Outcome Measure Data

Analysis Population Description

See Adverse Events Module for a complete summary of adverse events data.

Arm/Group Title	Akt/ERK Inhibitor ONC201	Akt/ERK Inhibitor ONC201, Methionine-restricted Diet
Arm/Group Description	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.	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.
Measure Participants	2	1
Count of Participants [Participants]	2 100%	1 50%

7. Other Pre-specified Outcome

Title	Time to Development or Worsening of Brain Metastases
Description	Will be summarized using Kaplan-Meier methodology.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

study was terminated early, data for outcome at 2 years not collected, see Number of Participants with Development or Worsening of Brain Metastases Outcome for more information

Arm/Group Title	Akt/ERK Inhibitor ONC201	Akt/ERK Inhibitor ONC201, Methionine-restricted Diet
Arm/Group Description	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.	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.
Measure Participants	0	0

8. Other Pre-specified Outcome

Title	Number of Participants With Developing or Worsening Brain Metastasis
Time Frame	up to 4 months

Outcome Measure Data

Analysis Population Description

one participant was determined to have a brain metastasis prior to treatment, outcome measure added to provide additional information about participant population

Arm/Group Title	Akt/ERK Inhibitor ONC201	Akt/ERK Inhibitor ONC201, Methionine-restricted Diet
Arm/Group Description	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.	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.
Measure Participants	1	1
Count of Participants [Participants]	0 0%	0 0%

Adverse Events

Time Frame	up to 4 months
Adverse Event Reporting Description	Participants were followed for 30 days after last dose of study drug
Arm/Group Title	Akt/ERK Inhibitor ONC201		Akt/ERK Inhibitor ONC201, Methionine-restricted Diet
Arm/Group Description	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.		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.
All Cause Mortality
	Akt/ERK Inhibitor ONC201		Akt/ERK Inhibitor ONC201, Methionine-restricted Diet
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/2 (100%)		1/1 (100%)
Serious Adverse Events
	Akt/ERK Inhibitor ONC201		Akt/ERK Inhibitor ONC201, Methionine-restricted Diet
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/2 (50%)		0/1 (0%)
Cardiac disorders
Pericardial tamponade	1/2 (50%)	1	0/1 (0%)	0
Pericardial effusion	1/2 (50%)	1	0/1 (0%)	0
Infections and infestations
Lung infection	1/2 (50%)	1	0/1 (0%)	0
Nervous system disorders
Intracranial hemorrhage	1/2 (50%)	1	0/1 (0%)	0
Other (Not Including Serious) Adverse Events
	Akt/ERK Inhibitor ONC201		Akt/ERK Inhibitor ONC201, Methionine-restricted Diet
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/2 (100%)		1/1 (100%)
Blood and lymphatic system disorders
Anemia	1/2 (50%)	1	1/1 (100%)	2
Eosinophilia	1/2 (50%)	1	0/1 (0%)	0
Eye disorders
Blurred vision	1/2 (50%)	1	0/1 (0%)	0
Vision decreased	1/2 (50%)	1	0/1 (0%)	0
Gastrointestinal disorders
Constipation	0/2 (0%)	0	1/1 (100%)	1
Diarrhea	1/2 (50%)	2	0/1 (0%)	0
Nausea	2/2 (100%)	2	1/1 (100%)	1
Vomiting	2/2 (100%)	4	0/1 (0%)	0
General disorders
Fatigue	2/2 (100%)	2	1/1 (100%)	1
Fever	1/2 (50%)	2	0/1 (0%)	0
Non-cardiac chest pain	1/2 (50%)	1	0/1 (0%)	0
Pain	1/2 (50%)	1	1/1 (100%)	2
Infections and infestations
Otitis media	0/2 (0%)	0	1/1 (100%)	1
Sinusitis	0/2 (0%)	0	1/1 (100%)	1
Urinary tract infection	1/2 (50%)	1	0/1 (0%)	0
Injury, poisoning and procedural complications
Bruising	0/2 (0%)	0	1/1 (100%)	1
Investigations
Aspartate aminotransferase increased	1/2 (50%)	1	0/1 (0%)	0
Blood bilirubin increased	1/2 (50%)	1	0/1 (0%)	0
Lymphocyte count decreased	1/2 (50%)	2	1/1 (100%)	1
White blood cell decreased	0/2 (0%)	0	1/1 (100%)	2
Metabolism and nutrition disorders
Anorexia	1/2 (50%)	1	0/1 (0%)	0
Hyperglycemia	2/2 (100%)	2	0/1 (0%)	0
Hypernatremia	0/2 (0%)	0	1/1 (100%)	1
Hypoalbuminemia	2/2 (100%)	2	0/1 (0%)	0
Hypomagnesemia	0/2 (0%)	0	1/1 (100%)	1
Hyponatremia	1/2 (50%)	1	0/1 (0%)	0
Nervous system disorders
Dizziness	1/2 (50%)	1	0/1 (0%)	0
Headache	2/2 (100%)	2	0/1 (0%)	0
Psychiatric disorders
Depression	1/2 (50%)	1	0/1 (0%)	0
Insomnia	1/2 (50%)	1	0/1 (0%)	0
Irritability	1/2 (50%)	2	0/1 (0%)	0
Renal and urinary disorders
Hemoglobinuria	1/2 (50%)	1	0/1 (0%)	0
Proteinuria	1/2 (50%)	1	0/1 (0%)	0
Reproductive system and breast disorders
Dyspnea	1/2 (50%)	1	1/1 (100%)	1

Limitations/Caveats

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

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.