IRB Study Number 23-965
Status Recruiting
Institute Taussig Cancer Institute
Description
4.2 Primary Objectives
The primary objective is to determine Progression-free Survival (PFS) per RECIST 1.1 in the study patient population as randomized [i.e., Intention-to-Treat (ITT) population]. Refer to Section 23.10.1 for details of this primary objective.
4.3 Secondary Objectives
Key secondary objectives are to determine Objective Response Rate (ORR) and Duration of Response (DOR) by RECIST 1.1 in the ITT patient population, PFS by RECIST 1.1 (in modified patient population), PFS by iRECIST, Overall Survival (OS) and safety in the ITT patient population. Refer to Section 23.12.1 for details of these secondary objectives.
Inclusion Criteria
Signed informed consent.
Women ≥ 18 years.
History of histologically confirmed (from prior treatment) non-resectable ovarian, fallopian tube or primary peritoneal cancer.
High-grade serous [including malignant mixed Mullerian tumor (MMMT) with metastasis that contains high grade epithelial carcinoma; FIGO grades 2 and 3 allowed], endometrioid, or clear-cell ovarian cancer.
Performance status ECOG of 0 or 1.
Life expectancy of at least 6 months.
Received a minimum of 3 prior lines (including the first line) of systemic therapy with no maximal limit.
Time from Last Platinum (TFLP) of ≤ 24 months since the last dose of platinum in the most recent platinum-based line of therapy (excluding using platinum as a radiosensitizer) until consent into this Phase 3 trial.
Platinum-resistant or -refractory disease based on platinum-free interval (PFI) by radiological assessment from the most recent platinum-based line of therapy (must have received a minimum of 2 doses of platinum in that line):
• Platinum-refractory: PFI of <1 month (including disease progression while on platinum-based therapy).
• Platinum-resistant: PFI of 1-6 months.
Received prior bevacizumab (or bevacizumab biosimilar) treatment.
No contraindication to receive carboplatin or cisplatin.
No contraindication to receive bevacizumab (or bevacizumab biosimilar).
Have disease progression after last prior line of therapy based on radiological assessment prior to randomization (from review of medical history records is allowed).
At least one measurable target lesion per RECIST 1.1 based on abdominal/pelvis screening imaging scan. Additional measurable target lesions by abdominal/pelvis and chest scans are allowed.
Patients in both Arms need to have evidence by CT and/or PET scans or physical exam of the abdominal/pelvic region of likely having disease within the peritoneal cavity (i.e., peritoneal carcinomatosis). Visual confirmation of visible lesions at time of catheter implantation for the Experimental Arm is not required.
Adequate renal, hepatic, bone marrow, and immune functions:
a. Renal function:
• Creatinine ≤ 1.8 mg/dL or calculated creatinine clearance (CrCl) using the Cockcroft-Gault formula ≥ 45 mL/min, or measured creatinine clearance ≥ 45 mL/min:
Female CrCl = (140 – age in years) × weight in kg × 0.85 72 × serum creatinine in mg/dL
• Absence of clinically significant hematuria on urinalysis: dipstick or urine sample ≤1+ (exception to this criterion is presence of renal stent(s) and/or with otherwise good renal function as assessed by investigator).
• Absence of clinically significant proteinuria on urinalysis: dipstick or urine sample ≤1+
b. Adequate hepatic function:
• Serum bilirubin ≤1.5 × ULN
• AST and ALT ≤ 3 × ULN
c. Adequate bone marrow function:
• ANC ≥ 1.5 × 109/L
• Platelets ≥ 100 × 109/L
• Stable Hemoglobin ≥ 80 g/L (transfusion in preparation for laparoscopy is allowed)
d. Adequate coagulation tests:
• INR ≤ 1.5 × ULN
e. Adequate immune function by lymphocyte count:
• Absolute Lymphocyte Count (ALC) ≥ 0.5 × 103/mm3
• Relative Lymphocyte Count (RLC) ≥ 10%
Have NO continuing acute toxic effects of any prior therapy, including but not limited to biological therapy, radiotherapy, chemotherapy, or surgical procedures, i.e., all such effects must have resolved to Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0) Grade 1 (with the exception of peripheral neuropathy and alopecia).
Women of child-bearing potential (WOCBP) must have a negative pregnancy test prior to initiating study dosing and must agree to use adequate contraception.
Be willing and able to comply with scheduled visits, the treatment plan, imaging and laboratory tests.
Adequate nutritional status as determined based on Prognostic Nutritional Index (PNI)*.
* PNI = 10 × serum albumin (g/dL) + 0.005 × peripheral lymphocyte count (i.e., Absolute Lymphocyte Count) (per mm3); minimal PNI is ≥ 35.
Exclusion Criteria
Tumors of mucinous, low-grade serous, squamous cell, small cell neuroendocrine subtypes, MMMT tumors absent an epithelial component on recent biopsy, or non-epithelial ovarian cancers (e.g., germ cell tumors, Sex-cord tumors).
Bowel obstruction within last 3 months prior to the time of screening.
Active urinary tract infection, pneumonia, or other systemic infections.
Active gastrointestinal bleeding.
Known current central nervous system (CNS) metastasis.
Inflammatory diseases of the bowel.
Concurrent therapy with any other investigational anti-cancer agent or treatments.
History of human immunodeficiency virus (HIV) infection.
Has active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection within 4 weeks prior to study initiation (as determined by serum sample).
History of thromboembolic event within the prior 3 months.
Pregnant or breast-feeding women.
Smallpox vaccination within 1 year of study therapy.
Any non-oncology vaccine therapy used for prevention of infectious diseases including seasonal (influenza) vaccinations, COVID-19 vaccination or other vaccines, within 2 weeks of the planned first dose of study drug.
Contraindications for IP catheter placement:
• Bowel obstruction with distended abdomen.
• Rigid abdomen with bulky anterior abdominal wall carcinomatosis.
• Abdominal wall hernia mesh that precludes laparoscopic entry to the abdomen.
At the time of eligibility assessment, have clinically significant cardiac disease (New York Heart Association Class III or IV).
Acute cerebrovascular event(s) (CVA, TIA) within the past 6 months.
Oxygen saturation <90% measured by pulse oximetry at rest.
Have received prior virus-based gene therapy or therapy with cytolytic virus of any type.
Receiving concurrent antiviral agent active against vaccinia virus (e.g., cidofovir, vaccinia immunoglobulin, imatinib, ST-246, or other agents with known anti-vaccinia activities).
Clinically significant dermatological disorders (e.g., eczema, psoriasis, or any unhealed skin wounds or ulcers) as assessed by the investigator.
Prior malignancy of other histology active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast, or any other stage I/II local malignancies.
Received chemotherapy, radiotherapy, or any anti-cancer biologic therapies within 4 weeks prior to the planned first dose of treatment in either Arm.
Underwent surgery within 4 weeks, or have insufficient recovery from surgical-related trauma or wound healing, prior to the planned first dose of treatment in either Arm.
Receiving immunosuppressive therapy or any steroids (exception is acute concurrent corticosteroid usage if no more than 20 mg per day for medical management with prednisolone equivalent).
Dementia or altered mental status that would prohibit informed consent.
Other severe or uncontrolled medical disorder that would, in the investigator’s opinion, impair ability to receive study treatment (e.g., uncontrolled diabetes, chronic renal disease, chronic pulmonary disease, active fever, psychiatric illness/social situations that would limit compliance with study requirements).
Known drug or alcohol abuse.
Symptomatic malignant ascites or pleural effusions defined as rapidly progressive ascites with abdominal distention and gastrointestinal dysfunction, pleural effusions with respiratory difficulties, and/or requiring frequent paracentesis more than once every 14 days.
Known hypersensitivity to gentamicin.
