RECRUITING

Modified Immune Cells (TAG72-CAR T Cells) for the Treatment of Patients With Platinum Resistant Epithelial Ovarian Cancer

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This phase I trial tests the safety, side effects, and best dose of TAG72-chimeric antigen receptor (CAR) T cells in treating patients with epithelial ovarian cancer that remains despite treatment with platinum therapy (platinum resistant). T cells are infection fighting blood cells that can kill tumor cells. The T cells given in this study will come from the patient and will have a new gene put in them that makes them able to recognize TAG72, a protein on the surface of tumor cells. These TAG72-specific T cells may help the body's immune system identify and kill TAG72+ cancer cells.

Official Title

A Phase 1 Study to Evaluate TAG72-Targeting Chimeric Antigen Receptor (CAR) T Cells in Patients With Advanced Epithelial Ovarian Cancer

Quick Facts

Study Start:2022-05-05

Study Completion:2027-04-05

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05225363

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:FEMALE

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Participant must have the ability to understand and the willingness to sign a written informed consent * Note: For research participants who do not speak English, a short form consent may be used with a City of Hope (COH) certified interpreter/translator to proceed with Pre-screening for TAG72 tumor expression, while the request for a translated full consent is processed. However, the research participant can proceed with lymphodepletion (if applicable) and CAR T cell infusion only after the translated full Screening/ Leukapheresis/ Treatment consent form is signed * Agreement to allow the use of archival tissue from diagnostic tumor biopsies. If unavailable exceptions may be granted with study principal investigator (PI) approval * Age \>= 18 years * Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2 or Karnofsky performance status (KPS) \>= 70% * Documented platinum resistant EOC (defined as disease that has progressed within six months of completing platinum therapy, or lack of response or disease progression while receiving the most recent platinum based therapy, respectively). Progression must be determined radiographically. Participant must have at least 1 measurable lesion * Documented TAG72+ (\> 1% cells \>= +1 intensity) tumor expression by IHC (MAb CC49) as evaluated by COH Pathology Core * In addition to platinum agents, participant must have received and failed, or have been intolerant to taxanes, liposomal doxorubicin or other agents known to confer clinical benefit. Participants are not required to fail all of these agents if, in the investigator's opinion, they would benefit from treatment on the current protocol * No known contraindications to leukapheresis, steroids or tocilizumab * Participant of reproductive potential must agree to use acceptable birth control methods throughout study therapy and for 3 months after final dose of study treatment * Total serum bilirubin =\< 2.0 mg/dL (performed within 42 days of signing the screening and leukapheresis consent) Patients with Gilbert syndrome may be included if their * total bilirubin is \< 3.0 x upper limit of normal (ULN) and direct bilirubin =\< 1.5 x ULN * Aspartate aminotransferase (AST) =\< 5 x ULN (performed within 42 days of signing the screening and leukapheresis consent) * Alanine aminotransferase (ALT) =\< 5 x ULN (performed within 42 days of signing the screening and leukapheresis consent) * Coagulation Parameters: Participants not receiving therapeutic anticoagulation: INR or aPTT ≤ 1.5xULN * Creatinine clearance of \>= 50 mL/min per the Cockcroft-Gault formula (performed within 42 days of signing the screening and leukapheresis consent) * Cardiac function (12 lead-electrocardiogram \[ECG\]) without acute abnormalities requiring investigation or intervention (performed within 42 days of signing the screening and leukapheresis consent) * Left ventricular ejection fraction \> 40% (performed within 42 days of signing the screening and leukapheresis consent)	* Participant has not yet recovered from toxicities of prior therapy * Participant with clinically significant arrhythmia or arrhythmias not stable on medical management within two weeks of signing the screening and leukapheresis consent * Participant with known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system, including seizure disorder * Active autoimmune disease requiring systemic immunosuppressive therapy * History of allergic reactions attributed to compounds of similar chemical or biologic composition or other agents used in this study * Current signs and/or symptoms of bowel obstruction * History of inflammatory bowel disease * History of gastrointestinal perforation or symptomatic diverticular disease confirmed by CT or colonoscopy * History of intra-abdominal abscess within the past 3 months. * Patients with known peritoneal adhesions that preclude the placement of an intraperitoneal catheter in the opinion of the surgeon placing the intraperitoneal catheter. * Participant with clinically significant arrhythmia or arrhythmias not stable on medical management within two weeks of signing the screening/leukapheresis/Treatment consent. * Participant with known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system, including seizure disorder. * Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia, and participants on therapeutic anti-coagulation. * History of stroke or intracranial hemorrhage within 6 months prior to signing the screening/ leukapheresis/Treatment consent * History of other malignancies, except for malignancy surgically resected (or treated with other modalities) with curative intent with no known active disease present for \>= 3 years, basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin * Uncontrolled active infection * Active hepatitis B or hepatitis C infection * Human immunodeficiency virus (HIV) infection * Any other condition that would, in the Investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns with clinical study procedures. * Massive ascites requiring therapeutic paracentesis will not be cause for ineligibility, per se, but will be evaluated on an individual basis. Investigators who have questions regarding assessing ascites are asked to speak with the Principal Investigator. * Prospective participants who, in the opinion of the Investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Inclusion Criteria

Exclusion Criteria

* Participant must have the ability to understand and the willingness to sign a written informed consent
* Note: For research participants who do not speak English, a short form consent may be used with a City of Hope (COH) certified interpreter/translator to proceed with Pre-screening for TAG72 tumor expression, while the request for a translated full consent is processed. However, the research participant can proceed with lymphodepletion (if applicable) and CAR T cell infusion only after the translated full Screening/ Leukapheresis/ Treatment consent form is signed
* Agreement to allow the use of archival tissue from diagnostic tumor biopsies. If unavailable exceptions may be granted with study principal investigator (PI) approval
* Age \>= 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2 or Karnofsky performance status (KPS) \>= 70%
* Documented platinum resistant EOC (defined as disease that has progressed within six months of completing platinum therapy, or lack of response or disease progression while receiving the most recent platinum based therapy, respectively). Progression must be determined radiographically. Participant must have at least 1 measurable lesion
* Documented TAG72+ (\> 1% cells \>= +1 intensity) tumor expression by IHC (MAb CC49) as evaluated by COH Pathology Core
* In addition to platinum agents, participant must have received and failed, or have been intolerant to taxanes, liposomal doxorubicin or other agents known to confer clinical benefit. Participants are not required to fail all of these agents if, in the investigator's opinion, they would benefit from treatment on the current protocol
* No known contraindications to leukapheresis, steroids or tocilizumab
* Participant of reproductive potential must agree to use acceptable birth control methods throughout study therapy and for 3 months after final dose of study treatment
* Total serum bilirubin =\< 2.0 mg/dL (performed within 42 days of signing the screening and leukapheresis consent) Patients with Gilbert syndrome may be included if their
* total bilirubin is \< 3.0 x upper limit of normal (ULN) and direct bilirubin =\< 1.5 x ULN
* Aspartate aminotransferase (AST) =\< 5 x ULN (performed within 42 days of signing the screening and leukapheresis consent)
* Alanine aminotransferase (ALT) =\< 5 x ULN (performed within 42 days of signing the screening and leukapheresis consent)
* Coagulation Parameters: Participants not receiving therapeutic anticoagulation: INR or aPTT ≤ 1.5xULN
* Creatinine clearance of \>= 50 mL/min per the Cockcroft-Gault formula (performed within 42 days of signing the screening and leukapheresis consent)
* Cardiac function (12 lead-electrocardiogram \[ECG\]) without acute abnormalities requiring investigation or intervention (performed within 42 days of signing the screening and leukapheresis consent)
* Left ventricular ejection fraction \> 40% (performed within 42 days of signing the screening and leukapheresis consent)

* Participant has not yet recovered from toxicities of prior therapy
* Participant with clinically significant arrhythmia or arrhythmias not stable on medical management within two weeks of signing the screening and leukapheresis consent
* Participant with known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system, including seizure disorder
* Active autoimmune disease requiring systemic immunosuppressive therapy
* History of allergic reactions attributed to compounds of similar chemical or biologic composition or other agents used in this study
* Current signs and/or symptoms of bowel obstruction
* History of inflammatory bowel disease
* History of gastrointestinal perforation or symptomatic diverticular disease confirmed by CT or colonoscopy
* History of intra-abdominal abscess within the past 3 months.
* Patients with known peritoneal adhesions that preclude the placement of an intraperitoneal catheter in the opinion of the surgeon placing the intraperitoneal catheter.
* Participant with clinically significant arrhythmia or arrhythmias not stable on medical management within two weeks of signing the screening/leukapheresis/Treatment consent.
* Participant with known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system, including seizure disorder.
* Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia, and participants on therapeutic anti-coagulation.
* History of stroke or intracranial hemorrhage within 6 months prior to signing the screening/ leukapheresis/Treatment consent
* History of other malignancies, except for malignancy surgically resected (or treated with other modalities) with curative intent with no known active disease present for \>= 3 years, basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin
* Uncontrolled active infection
* Active hepatitis B or hepatitis C infection
* Human immunodeficiency virus (HIV) infection
* Any other condition that would, in the Investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns with clinical study procedures.
* Massive ascites requiring therapeutic paracentesis will not be cause for ineligibility, per se, but will be evaluated on an individual basis. Investigators who have questions regarding assessing ascites are asked to speak with the Principal Investigator.
* Prospective participants who, in the opinion of the Investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Contacts and Locations

Study Contact

Lorna Rodriguez

CONTACT

626-359-8111

lorrodriguez@coh.org

Principal Investigator

Lorna Rodriguez

PRINCIPAL_INVESTIGATOR

City of Hope Medical Center

Study Locations (Sites)

City of Hope Medical Center

Duarte, California, 91010

United States

Collaborators and Investigators

Sponsor: City of Hope Medical Center

Lorna Rodriguez, PRINCIPAL_INVESTIGATOR, City of Hope Medical Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-05-05

Study Completion Date2027-04-05

Study Record Updates

Study Start Date2022-05-05

Study Completion Date2027-04-05

Terms related to this study

Additional Relevant MeSH Terms

Platinum-Resistant Ovarian Carcinoma