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ONC201 and Atezolizumab in Obesity-Driven Endometrial Cancer

Primary Purpose

Endometrial Cancer, Metastasis

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Atezolizumab

ONC201

About this trial

This is an interventional treatment trial for Endometrial Cancer focused on measuring Atezolizumab, ONC201, obesity

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

In order to participate in this study a subject must meet all of the eligibility criteria outlined below.

Inclusion Criteria

Ability to understand and willingness to sign a written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information.
Age ≥ 18 years at the time of consent.
ECOG Performance Status of 0, 1, or 2
Histologically confirmed metastatic or recurrent EC (endometrioid, serous, clear cell, adeno-squamous and mixed histologies).
Subjects must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension in accordance with RECIST criteria
Must have radiographic disease progression after at least 1 line of systemic cytotoxic therapy for metastatic disease or with progression within 12 months of completing adjuvant chemotherapy.
Life expectancy of at least 3 months.
Demonstrate adequate organ function as defined in the table below; all screening labs to be obtained within 72 hours prior to initiating study treatment.

Exclusion Criteria

Prior treatment with ONC201.
Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including antiCTLA-4, and anti PD-L1 therapeutic antibodies
Treatment with another investigational agent or participation in another clinical trial within the last 28 days prior to initiating protocol therapy.
Subjects who have had chemotherapy or radiotherapy within 4 weeks prior to study treatment or those who have not recovered from adverse events due to agents administered more than 4 weeks prior to initiating protocol therapy.
Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of protocol therapy Subjects receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of protocol therapy.
Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti TNF-agents) within 2 weeks prior to initiation

Sites / Locations

Lineberger Comprehensive Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Obese

Non-Obese

Arm Description

Subjects with BMI > 30 kg/m2

Subjects with BMI ≤ 29.9 kg/m2

Outcomes

Primary Outcome Measures

Recommended phase 2 dose (RP2D)

The RP2D will be determined based on the incidence of dose-limiting toxicities (DLT)s. A DLT is defined as all grade 3 or above toxicities that are related to study treatment and occur within the first cycle of therapy. Adverse events are assessed using NCI Common Terminology Criteria for Adverse Events (CTCAE). A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate Instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.

Secondary Outcome Measures

Overall Response Rate (ORR)

ORR is defined as the proportion of subjects achieving response complete response (CR) or partial response(PR) assessed by RECIST v1.1. Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): >=30% decrease in the sum of the longest diameter of target lesions.

Progression Free Survival (PFS)

PFS is defined as time from first day of treatment until disease progression as defined by RECIST v1.1 or death from any cause.

Overall Survival (OS)

OS is defined as the time of the start of study treatment to death from any cause.

Full Information

NCT ID

NCT05542407

First Posted

September 12, 2022

Last Updated

September 7, 2023

Sponsor

UNC Lineberger Comprehensive Cancer Center

Collaborators

Genentech, Inc., Oncoceutics, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT05542407

Brief Title

ONC201 and Atezolizumab in Obesity-Driven Endometrial Cancer

Official Title

Phase 1 Clinical Trial of ONC201 and Atezolizumab in Obesity-Driven Endometrial Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Recruiting

Study Start Date

August 16, 2023 (Actual)

Primary Completion Date

January 15, 2025 (Anticipated)

Study Completion Date

January 15, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

UNC Lineberger Comprehensive Cancer Center

Collaborators

Genentech, Inc., Oncoceutics, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Endometrial cancer (EC) is the fourth most common cancer in United States women, and alarmingly, the frequency and mortality from EC continues to rise, in part due to the obesity epidemic. Obese women with EC have a 6.3-fold increased risk of death from this disease, as compared to their non-obese counterparts. Patients with advanced/recurrent EC are unlikely to be cured by surgery, conventional chemotherapy (paclitaxel + carboplatin is the standard first-line treatment), radiation, or a combination of these. Thus, new treatments for EC are desperately needed as well as a better understanding of the impact of obesity on EC biology and treatment. The purpose of this study is to test the safety of a combination of treatments, atezolizumab and ONC201, given based on body weight, to treat endometrial cancer. Using the combination of atezolizumab and ONC201, has not been approved by the Food and Drug Administration (FDA) for the treatment of endometrial cancer. This clinical trial will examine the treatment of atezolizumab + ONC201 in obese and non-obese subjects with metastatic/recurrent EC.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Endometrial Cancer, Metastasis

Keywords

Atezolizumab, ONC201, obesity

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

58 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Obese

Arm Type

Experimental

Arm Description

Subjects with BMI > 30 kg/m2

Arm Title

Non-Obese

Arm Type

Experimental

Arm Description

Subjects with BMI ≤ 29.9 kg/m2

Intervention Type

Drug

Intervention Name(s)

Atezolizumab

Intervention Description

10 mg/kg- 20 mg/kg Atezolizumab will be administered by intravenous, on day 1 of each 21-day cycle.

Intervention Type

Drug

Intervention Name(s)

ONC201

Intervention Description

375 mg once weekly - 625 mg ONC201 will be administered orally, once or twice weekly.

Primary Outcome Measure Information:

Title

Recommended phase 2 dose (RP2D)

Description

Time Frame

Up to 3 weeks

Secondary Outcome Measure Information:

Title

Overall Response Rate (ORR)

Description

Time Frame

Up to 2 years

Title

Progression Free Survival (PFS)

Description

PFS is defined as time from first day of treatment until disease progression as defined by RECIST v1.1 or death from any cause.

Time Frame

Up to 2 years

Title

Overall Survival (OS)

Description

OS is defined as the time of the start of study treatment to death from any cause.

Time Frame

Up to 2 years

10. Eligibility

Sex

Female

Gender Based

Yes

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

In order to participate in this study a subject must meet all of the eligibility criteria outlined below. Inclusion Criteria Ability to understand and willingness to sign a written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information. Age ≥ 18 years at the time of consent. ECOG Performance Status of 0, 1, or 2 Histologically confirmed metastatic or recurrent EC (endometrioid, serous, clear cell, adeno-squamous and mixed histologies). Subjects must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension in accordance with RECIST criteria Must have radiographic disease progression after at least 1 line of systemic cytotoxic therapy for metastatic disease or with progression within 12 months of completing adjuvant chemotherapy. Life expectancy of at least 3 months. Demonstrate adequate organ function as defined in the table below; all screening labs to be obtained within 72 hours prior to initiating study treatment. Exclusion Criteria Prior treatment with ONC201. Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including antiCTLA-4, and anti PD-L1 therapeutic antibodies Treatment with another investigational agent or participation in another clinical trial within the last 28 days prior to initiating protocol therapy. Subjects who have had chemotherapy or radiotherapy within 4 weeks prior to study treatment or those who have not recovered from adverse events due to agents administered more than 4 weeks prior to initiating protocol therapy. Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of protocol therapy Subjects receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study. Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of protocol therapy. Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti TNF-agents) within 2 weeks prior to initiation

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

De'Andrea Taylor

Phone

919-966-1195

deandrea_taylor@med.unc.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Victoria Bae-Jump, MD, PhD

Organizational Affiliation

UNC-Chapel Hill

Official's Role

Principal Investigator

Facility Information:

Facility Name

Lineberger Comprehensive Cancer Center

City

Chapel Hill

State/Province

North Carolina

ZIP/Postal Code

27599

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Melisa Ramirez-Pineda

Phone

919-966-5996

Melisa_Ramirez-Pineda@med.unc.edu

First Name & Middle Initial & Last Name & Degree

Victoria Bae-Jump, M.D., PhD

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.

Links:

URL

http://unclineberger.org/patientcare/clinical-trials/clinical-trials

Description

University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trials

Learn more about this trial

ONC201 and Atezolizumab in Obesity-Driven Endometrial Cancer

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