RECRUITING

Clinical Trial of Autologous B7-H3 CAR T Cells in Reoccurent Platinum-resistant Ovarian Tumors

Conditions

Quick Navigation

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 is a single site, open label, Phase 1 study using a 3 + 3 dose escalation design in two cohorts of adults with recurrent, platinum-resistant ovarian tumors.

Official Title

Phase I Clinical Trial of Autologous B7-H3 Chimeric Receptor (CAR) T Cells in Adults With Recurrent, Platinum Resistant Ovarian Tumors

Quick Facts

Study Start:2024-11-11

Study Completion:2025-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06646627

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
1. Disease: Histologically or cytologically confirmed diagnosis of ovarian cancer including serous, endometrioid, clear cell, mucinous, mixed epithelial, or undifferentiated. The study does not include pure sarcoma, stromal, or germ-cell tumors. Tumors that are substantially high-grade carcinoma and have focal elements of lower grade tumors or sarcomatous elements (e.g., carcinosarcoma) are eligible. 2. Have measurable disease. Measurable disease is defined as at least 1 lesion that can be accurately measured in at least 1 dimension (longest diameter to be recorded). Each lesion must be ≥10 mm when measured by CT, MRI, or caliper measurement at clinical examination or ≥20 mm when measured by chest x-ray. Lymph nodes must be ≥15 mm in short axis when measured by CT or MRI. 3. B7-H3 positive expression on malignant cells is NOT required but archival tissue must be available, or the subject must be willing to undergo tissue biopsy for expression analysis. 4. Age: ≥ 18 years of age 5. Prior Therapies: Subjects must have had at least 1 prior platinum-based chemotherapeutic regimen for the management of ovarian carcinoma. 6. Performance Status: ECOG status of 2 or better (or Karnofsky Performance Status score of ≥60%) (See Section 11.1) 7. Life expectancy at least 3 months, in the investigator's clinical judgement. 8. Adequate bone marrow and major organ function. * Hgb ≥ 10 g/dL * ANC ≥ 1500/uL * Platelet count ≥ 100,000/uL * Absolute lymphocyte count ≥150/uL * Creatinine ≤ 1.5 mg/dL or creatinine clearance ≥ 50 mL/min * Serum ALT and AST ≤ 5x ULN (Grade 2) * Total bilirubin ≤ 1.5x ULN (subjects with Gilbert's syndrome allowed if direct bilirubin within normal limits) * PT or PTT ≤ 1.25 X ULN (not receiving therapeutic anticoagulation) * Cardiac ejection fraction ≥ 45% * No evidence of physiologically significant pericardial effusion * No clinically significant ECG findings * Baseline oxygen saturation \> 92% on room air 9. Pregnancy: Females of childbearing potential (defined as women ≤50 years of age, or \>50 years of age with a history of amenorrhea for ≤12 months prior to study entry) must have a negative blood or urine pregnancy test. 10. Consent: Must be able to understand and be willing to personally sign the written IRB approved informed consent document.	* 1. Active infection or uncontrollable infection requiring systemic treatment within 1 week before screening. Simple UTI and uncomplicated bacterial pharyngitis are permitted if responding to active treatment. 2. Requirement for systemic corticosteroid therapy at doses higher than physiologic maintenance dosing (must be \< 5 mg/day of prednisone (or equivalent doses of other corticosteroids). Topical, inhaled or ocular steroids are allowed. 3. Presence of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess. 4. Malignant tumors other than the target tumor within 2 years prior to screening, except for the following: malignant tumors that have received radical treatment and no known active disease within ≥ 2 years prior to enrollment; or adequately treated non-melanoma skin cancers with no evidence of disease. 5. Have any of the following heart conditions: * Myocardial infarction or coronary artery bypass grafting (CABG) within 6 months before enrollment; * Clinically significant ventricular arrhythmia, or a history of unexplained syncope (except those caused by vasovagal or dehydration); * History of severe nonischemic cardiomyopathy. 6. Known to have active or uncontrolled autoimmune diseases, such as Crohns disease, rheumatoid arthritis, systemic lupus erythematosus, systemic vasculitis, etc. 7. Ongoing HIV, HBV, or HCV infection. History of HBV or HCV is permitted if viral load is undetectable by qPCR and/or nucleic acid testing. 8. Known or suspected untreated brain metastases. Patients with radiographically stable, asymptomatic previously irradiated lesions are eligible provided patient is \>4 weeks beyond completion of cranial irradiation and \>3 weeks off of corticosteroid therapy at the time of study intervention. 9. Known sensitivities to any of the agents used in this study or their reagents including steroids, tocilizumab, DSMO, cyclophosphamide, fludarabine, etc. 10. Prior history of clinically significant seizure disorder (e.g., not including childhood febrile seizures). 11. Any other issue which, in the opinion of the treating physician or principal investigator, would make the patient ineligible for the study.

Inclusion Criteria

Exclusion Criteria

1. Disease: Histologically or cytologically confirmed diagnosis of ovarian cancer including serous, endometrioid, clear cell, mucinous, mixed epithelial, or undifferentiated. The study does not include pure sarcoma, stromal, or germ-cell tumors. Tumors that are substantially high-grade carcinoma and have focal elements of lower grade tumors or sarcomatous elements (e.g., carcinosarcoma) are eligible.
2. Have measurable disease. Measurable disease is defined as at least 1 lesion that can be accurately measured in at least 1 dimension (longest diameter to be recorded). Each lesion must be ≥10 mm when measured by CT, MRI, or caliper measurement at clinical examination or ≥20 mm when measured by chest x-ray. Lymph nodes must be ≥15 mm in short axis when measured by CT or MRI.
3. B7-H3 positive expression on malignant cells is NOT required but archival tissue must be available, or the subject must be willing to undergo tissue biopsy for expression analysis.
4. Age: ≥ 18 years of age
5. Prior Therapies: Subjects must have had at least 1 prior platinum-based chemotherapeutic regimen for the management of ovarian carcinoma.
6. Performance Status: ECOG status of 2 or better (or Karnofsky Performance Status score of ≥60%) (See Section 11.1)
7. Life expectancy at least 3 months, in the investigator's clinical judgement.
8. Adequate bone marrow and major organ function.
* Hgb ≥ 10 g/dL
* ANC ≥ 1500/uL
* Platelet count ≥ 100,000/uL
* Absolute lymphocyte count ≥150/uL
* Creatinine ≤ 1.5 mg/dL or creatinine clearance ≥ 50 mL/min
* Serum ALT and AST ≤ 5x ULN (Grade 2)
* Total bilirubin ≤ 1.5x ULN (subjects with Gilbert's syndrome allowed if direct bilirubin within normal limits)
* PT or PTT ≤ 1.25 X ULN (not receiving therapeutic anticoagulation)
* Cardiac ejection fraction ≥ 45%
* No evidence of physiologically significant pericardial effusion
* No clinically significant ECG findings
* Baseline oxygen saturation \> 92% on room air
9. Pregnancy: Females of childbearing potential (defined as women ≤50 years of age, or \>50 years of age with a history of amenorrhea for ≤12 months prior to study entry) must have a negative blood or urine pregnancy test.
10. Consent: Must be able to understand and be willing to personally sign the written IRB approved informed consent document.

* 1. Active infection or uncontrollable infection requiring systemic treatment within 1 week before screening. Simple UTI and uncomplicated bacterial pharyngitis are permitted if responding to active treatment.
2. Requirement for systemic corticosteroid therapy at doses higher than physiologic maintenance dosing (must be \< 5 mg/day of prednisone (or equivalent doses of other corticosteroids). Topical, inhaled or ocular steroids are allowed.
3. Presence of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess.
4. Malignant tumors other than the target tumor within 2 years prior to screening, except for the following: malignant tumors that have received radical treatment and no known active disease within ≥ 2 years prior to enrollment; or adequately treated non-melanoma skin cancers with no evidence of disease.
5. Have any of the following heart conditions:
* Myocardial infarction or coronary artery bypass grafting (CABG) within 6 months before enrollment;
* Clinically significant ventricular arrhythmia, or a history of unexplained syncope (except those caused by vasovagal or dehydration);
* History of severe nonischemic cardiomyopathy. 6. Known to have active or uncontrolled autoimmune diseases, such as Crohns disease, rheumatoid arthritis, systemic lupus erythematosus, systemic vasculitis, etc.
7. Ongoing HIV, HBV, or HCV infection. History of HBV or HCV is permitted if viral load is undetectable by qPCR and/or nucleic acid testing.
8. Known or suspected untreated brain metastases. Patients with radiographically stable, asymptomatic previously irradiated lesions are eligible provided patient is \>4 weeks beyond completion of cranial irradiation and \>3 weeks off of corticosteroid therapy at the time of study intervention.
9. Known sensitivities to any of the agents used in this study or their reagents including steroids, tocilizumab, DSMO, cyclophosphamide, fludarabine, etc.
10. Prior history of clinically significant seizure disorder (e.g., not including childhood febrile seizures).
11. Any other issue which, in the opinion of the treating physician or principal investigator, would make the patient ineligible for the study.

Contacts and Locations

Study Contact

Bela Shah

CONTACT

650-723-0594

belashah@stanford.edu

Principal Investigator

Oliver Dorigo, MD, PhD

PRINCIPAL_INVESTIGATOR

Stanford University

Study Locations (Sites)

Stanford University

Palo Alto, California, 94304

United States

Collaborators and Investigators

Sponsor: Crystal Mackall, MD

Oliver Dorigo, MD, PhD, PRINCIPAL_INVESTIGATOR, Stanford University

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 Date2024-11-11

Study Completion Date2025-12

Study Record Updates

Study Start Date2024-11-11

Study Completion Date2025-12

Terms related to this study

Keywords Provided by Researchers

B7-H3CART

Additional Relevant MeSH Terms

Ovarian Cancer