Clinical Trials Logo

Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT05081492
Other study ID # 21094
Secondary ID NCI-2021-0898321
Status Active, not recruiting
Phase Phase 1
First received
Last updated
Start date October 18, 2021
Est. completion date September 22, 2024

Study information

Verified date January 2024
Source City of Hope Medical Center
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This phase I trial tests the safety, side effects, and best dose of CF33-hNIS-antiPDL1 in treating patients with triple negative breast cancer that has spread to other places in the body (metastatic). CF33-hNIS-antiPDL1 is an oncolytic virus. This is a virus that is designed to infect tumor cells and break them down.


Description:

PRIMARY OBJECTIVE: I. To determine the safety and tolerability of a novel chimeric oncolytic orthopoxvirus, oncolytic virus CF33-expressing hNIS/Anti-PD-L1 antibody (CF33-hNIS-antiPDL1), by the evaluation of toxicities including: type, frequency, severity, attribution, time course, reversibility and duration according to Common Terminology Criteria for Adverse Events (CTCAE) 5.0 criteria. SECONDARY OBJECTIVES: I. To determine the optimal biologic dose (OBD) (defined as a safe dose that induces an immune response in tumors [increase checkpoint target PD-L1 by at least 5% and/or increase T cell infiltration by at least 10%]) and the recommended phase II dose (RP2D) for future expansion trial. II. To determine tumor response rates by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 (primary) and immune-modified (i)RECIST (secondary). III. To document possible therapeutic efficacy and evaluate progression-free survival, overall survival and response. EXPLORATORY OBJECTIVE: I. To determine the immune and genomic profiles of tumors before and after CF33-hNIS-antiPDL1 therapy. OUTLINE: This is a dose-escalation study. Patients receive CF33-hNIS-antiPDL1 intratumorally (IT) on days 1 and 15. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days, then every 3 months for 1 year.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 9
Est. completion date September 22, 2024
Est. primary completion date September 22, 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Documented informed consent of the participant and/or legally authorized representative - Assent, when appropriate, will be obtained per institutional guidelines - Agreement to research biopsies on study, once during study and end of study, exceptions may be granted with study principal investigator (PI) approval - >= 18 years - Eastern Cooperative Oncology Group (ECOG) =< 2 - Histologically confirmed metastatic triple negative breast cancer. Triple negative status will be defined as estrogen receptor (ER) and progesterone receptor (PR) =< 10% by immunohistochemistry (IHC) and HER2 negative, per American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines - Measurable disease by RECIST 1.1 - Patients must have progressed on or been intolerant of at least 2 prior lines of therapy for advanced/metastatic disease. Patients that qualify for immunotherapy and/or PARP inhibitors must have progressed on or been intolerant of these agents - Fully recovered from the acute toxic effects (except alopecia) to =< grade 2 to prior anti-cancer therapy - Must have a superficial tumor (cutaneous, subcutaneous), breast lesion or nodal metastases amenable to safe repeated intratumoral injections per treating physician and interventional radiologist review - Absolute neutrophil count (ANC) >= 1,500/mm^3 - NOTE: Growth factor is not permitted within 14 days of ANC assessment unless cytopenia is secondary to disease involvement - Platelets >= 100,000/mm^3 - NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment unless cytopenia is secondary to disease involvement - Total bilirubin =< 1.5 X upper limit of normal (ULN) - Aspartate aminotransferase (AST) =< 2.5 x ULN - If liver metastases are present: AST =< 5 x ULN - Alanine aminotransferase (ALT) =< 2.5 x ULN - If liver metastases are present: ALT =< 5 x ULN - Serum creatinine =< 1.5 mg/dL or creatinine clearance of >= 50 mL/min per 24 hour urine test or the Cockcroft-Gault formula - Prothrombin (PT) =< 1.5 x ULN - Activated partial thromboplastin time (aPTT) =< 1.5 x ULN - Women of childbearing potential (WOCBP): negative serum pregnancy test - Agreement by females and males of childbearing potential* and their partners to use an effective method of birth control (defined as a hormonal or barrier method) or abstain from heterosexual activity for the course of the study through at least 6 months after the last dose of protocol therapy - Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only) Exclusion Criteria: - Chemotherapy, biological therapy, immunotherapy or investigational therapy within 14 days prior to day 1 of protocol therapy - Major surgery or radiation therapy within 28 days of study therapy - Has received a vaccination within 30 days of first study injection - History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent - Clinically significant uncontrolled illness - Active infection requiring antibiotics - Known history of immunodeficiency virus (HIV) - Patients with a known history of hepatitis B or hepatitis C infection who have active disease as evidenced by hepatitis (Hep) B surface antigen status or Hep C polymerase chain reaction (PCR) status obtained within 14 days of cycle 1, day 1 - Another malignancy within 3 years, except non-melanomatous skin cancer - Females only: Pregnant or breastfeeding - Patients may not have clinically unstable brain metastases. Patients may be enrolled with a history of treated brain metastases that are clinically stable for >= 4 weeks prior to start of study treatment - Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures - 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)

Study Design


Related Conditions & MeSH terms


Intervention

Biological:
Oncolytic Virus CF33-expressing hNIS/Anti-PD-L1 Antibody
Given IT

Locations

Country Name City State
United States City of Hope Medical Center Duarte California

Sponsors (3)

Lead Sponsor Collaborator
City of Hope Medical Center Imugene Limited, National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Incidence of adverse events Toxicity will be graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events version 5.0. Observed toxicities/adverse events will be summarized in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study treatment and reversibility or outcome. Up to 30 days
Secondary Immune Biomarker Expression Changes (%) in PD1 expression compared to baseline by immunohistochemistry
Changes (%) in PD-L1 expression compared to baseline by immunohistochemistry
Changes (%) CTLA-4 expression compared to baseline by immunohistochemistry
Changes (%) CD8 cell quantification compared to baseline by Immunohistochemistry
Up to 6 months
Secondary Optimal biologic dose Defined as safe dose that induces an immune response in tumors (increase checkpoint target PD-L1 by at least 5% and/or increase T cell infiltration by at least 10%). Up to 3 months
Secondary Response rate based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Will estimate the response rate by the percent of evaluable patients and its 95% confidence interval (C.I.) by the exact method. Up to 6 months
Secondary Response rate based on immune related iRECIST Will estimate the response rate by the percent of evaluable patients and its 95% C.I. by the exact method. Up to 6 months
Secondary Progression free survival Will be estimated using the Kaplan-Meier product-limit method. Up to 1 year
Secondary Clinical benefit rate Percentage of patients who achieved Partial Response/ Complete Response/ Stable disease at 6 months Up to 6 months
Secondary Event-free survival Event-free survival (EFS): defined as the duration of time from start of protocol treatment to time of disease relapse/progression or death due to any cause, whichever occurs earlier. Up to 3 years
Secondary Duration of response Duration of response (DOR): defined as the time from the first achievement of PR and CR to time of PD. Up to 3 years
Secondary Overall survival Will be estimated using the Kaplan-Meier product-limit method. Up to 3 years
See also
  Status Clinical Trial Phase
Suspended NCT05673200 - Testing the Addition of an Anti-cancer Drug, ASTX727 (Cedazuridine, Decitabine), to Chemotherapy (Paclitaxel) and Immunotherapy (Pembrolizumab) for Metastatic Triple-Negative Breast Cancer Phase 1
Active, not recruiting NCT03218826 - PI3Kbeta Inhibitor AZD8186 and Docetaxel in Treating Patients Advanced Solid Tumors With PTEN or PIK3CB Mutations That Are Metastatic or Cannot Be Removed by Surgery Phase 1
Recruiting NCT04521764 - A Vaccine (MV-s-NAP) for the Treatment of Patients With Invasive Metastatic Breast Cancer Phase 1
Recruiting NCT03723928 - S1703 Serum Tumor Marker Directed Disease Monitoring in Patients With Hormone Receptor Positive Her2 Negative Metastatic Breast Cancer N/A
Suspended NCT03737695 - Clinical Information and Biospecimen Collection From Patients With Recurrent or Stage IV Breast Cancer
Active, not recruiting NCT04316117 - Using FDG-PET/CT to Assess Response of Bone-Dominant Metastatic Breast Cancer, FEATURE Study Phase 2
Not yet recruiting NCT04529044 - 177Lu-DOTATATE for the Treatment of Stage IV or Recurrent Breast Cancer Phase 2
Recruiting NCT04862585 - Safely Stopping Pre-medications in Patients With Breast Cancer Who Are Receiving Paclitaxel Phase 2/Phase 3
Completed NCT00338728 - Letrozole and Imatinib Mesylate in Treating Postmenopausal Participants With Estrogen or Progesterone Positive Metastatic Breast Cancer Phase 2
Withdrawn NCT05967286 - Olaparib and Alpelisib for Treatment of Metastatic Breast Cancer, A ComboMATCH Treatment Trial Phase 2
Recruiting NCT04673448 - Niraparib and TSR-042 for the Treatment of BRCA-Mutated Unresectable or Metastatic Breast, Pancreas, Ovary, Fallopian Tube, or Primary Peritoneal Cancer Phase 1
Recruiting NCT05318469 - Ivermectin and Balstilimab for the Treatment of Metastatic Triple Negative Breast Cancer Phase 1/Phase 2
Not yet recruiting NCT05539365 - Dendritic Cell-Based Treatment Plus Immunotherapy for the Treatment of Metastatic or Unresectable Triple Negative Breast Cancer Phase 2
Terminated NCT05198843 - Testing an Omega-3 Fatty Acid-Based Anti-Cancer Therapy for Patients With Triple-Negative Inflammatory Breast Cancer That Has Spread to Other Parts of the Body Phase 1/Phase 2
Active, not recruiting NCT04514484 - Testing the Combination of the Anti-cancer Drugs XL184 (Cabozantinib) and Nivolumab in Patients With Advanced Cancer and HIV Phase 1
Recruiting NCT05751668 - Finding an Effective Dose of GM1 to Reduce or Prevent Neuropathy (Numbness or Weakness) Due to Treatment With Paclitaxel (Phase II) Phase 2
Suspended NCT04906369 - Optimizing Treatment of Stage IV Breast Cancer Through Real-Time Disease Monitoring
Completed NCT03291938 - IACS-010759 in Advanced Cancers Phase 1
Recruiting NCT04314401 - National Cancer Institute "Cancer Moonshot Biobank"
Withdrawn NCT04351230 - T-DM1 With or Without Abemaciclib for the Treatment of HER2-Positive Metastatic Breast Cancer Phase 2