A Multicenter, Phase Ib/II Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Clinical Activity of TUB-040, in Combination with Standard Ovarian Cancer Drugs in Patients with High-grade Epithelial Serous or Endometrioid Epithelial Ovarian Cancer (OC).
Study Identifier:
NAPISTAR 1-02
CT.gov Identifier:
N/A
EudraCT Identifier:
EU Trial (CTIS) Number:
Study Contact Information:
N/A
Recruiting
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Study Summary
To evaluate the safety, tolerability, pharmacokinetics and preliminary clinical activity of TUB-040, in combination with standard ovarian cancer drugs in patients with high-grade epithelial serous or endometrioid epithelial ovarian cancer (OC).
Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Ovarian
Fallopian Tube
Primary Peritoneal
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
Phase I/II
Sex
Female
Age
18+ years
Study Drug
Drug: Test: TUB-040 Intravenous infusion + Standard Chemo therapy
Study Status
Indicates the current recruitment status or the expanded access status
Recruiting
Requirements information
Inclusion criteria
- Female ≥ 18 years of age at the time of the first screening visit.2Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.3Histologically confirmed advanced high-grade serous or endometrioid epithelial ovarian, fallopian tube or primary peritoneal cancer.4Have XXX ovarian cancer (XXOC) defined as: Patients who had recurrences (radiologically confirmed) to XXX-based therapy and have responded to the last XXX therapy received before study entry and did not progress within 6 months (182 days) of the date of the last dose of XXX-based systemic treatment.5Radiologically measurable disease in at least 1 lesion by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, that can include a lesion in an irradiated field and that shows progression according to RECIST v1.1.6Patients must have progressed radiographically on or after their most recent line of anti-cancer therapy.7Adequate hematologic function as indicated by: a) Platelet counts 100,000/mm³ (no transfusion or growth factors e.g. eltrombopag, romiplostim, or IL-11 within 4 weeks before first dose) b) Hemoglobin ≥9.0 g/dL (no transfusion or growth factors e.g. erythropoietin [EPO], darbepoetin within 4 weeks before first dose or long-acting white blood cell growth factors within 20 days before first dose) c) Absolute neutrophil count (ANC) ≥1500/μL (no growth factors, e.g., G-CSF, GM-CSF within 4 weeks before first dose) d) International normalized ratio (INR) ≤1.5 and activated partial thromboplastin time (aPTT) ≤1.5 × ULN in the absence of anticoagulation therapy. If patients are on anticoagulation therapy with a specific INR goal, INR should be within the therapeutic range for the medical indication.8Adequate hepatic function defined as total bilirubin level ≤1.5 × ULN, an aspartate aminotransferase (AST) level ≤2.5 × ULN, and an alanine aminotransferase (ALT) level ≤2.5 × ULN. a) For documented Gilbert's Syndrome, a total bilirubin <3 × ULN is accepted. b) For patients with liver metastases, AST and ALT <5 × ULN is accepted.9Alkaline phosphatase < 2.5 x ULN, except if there is an alternative explanation for ALP elevation rather than hepatic failure, such as the presence of bone metastasis.10Adequate renal function defined by glomerular filtration rate ≥60 mL/min (according to the Chronic Kidney Disease Epidemiology Collaboration, CKD-EPI, formula).11Patients must be willing to sign an archival tissue release form for research purposes and determination of biomarker (e.g., NaPi2b) expression. The patient must have an adequate tumor tissue sample available for biomarker assessment by the central laboratory. Mandatory is either a tissue (FFPE) block or a minimum of 6 freshly cut unstained sections based on the most recently available tumor sample. If no archival specimens are available, a new biopsy must be performed.12Resolution of all acute toxic effects of prior therapy or surgical procedures to Grade ≤1 including peripheral neuropathy (except alopecia, hyperpigmentation, or discoloration (incl. vitiligo) of the skin and nails, stable immune-related toxicity such as hypothyroidism on hormone replacement, corticosteroid treatment on ≤10 mg daily prednisone (or equivalent).13Patients with previous systemic topoisomerase 1 inhibitor treatment (e.g., Topotecan) or patients that are previously treated with ADCs are allowed (except for ADCs with a topoisomerase 1 inhibitor, such as SN38 or other camptothecin derivatives as payload or any ADC targeting NaPi2b).14Completed washout of prior therapy: a. Systemic anti-neoplastic therapy: five half-lives or 4 weeks, whichever is shorter prior to first dose of study drug. Hormonal therapy is not considered anti-neoplastic therapy. b. Radiotherapy: last dose ≥ 2 weeks from first dose of study drug. c. Completed major surgery at least 4 weeks prior from first dose of study drug and recovered from side effects to Grade ≤1.15Viral infections: a) Patients who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B (HBV) anti-viral therapy for at least 4 weeks and have undetectable HBV viral load. b) Patients with history of hepatitis C viral (HCV) infection are eligible if HCV viral load is undetectable at screening.16Women of childbearing potential (WOCBP) who are sexually active with a non-sterilized partner must use at least 1 highly effective method of contraception (with a failure rate of ≤1% per year) from the time of screening and must agree to continue using such precautions until the end of exposure, plus at minimum 5 half-lives and 6 months after last dose of either TUB-040, carboplatin, or bevacizumab, whichever is later. Abstinence is acceptable only when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception.17Patients must agree to continue a highly effective contraceptive method, refrain from egg cell donation and breastfeeding while on study treatment and for 5 half-lives plus 6 months after the last dose of study treatment.18Female patients will be considered post-menopausal if they have undergone bilateral salpingectomy, and/or bilateral oophorectomy, and/or hysterectomy or have been amenorrheic for 12 months without an alternative medical cause. a) Women <50 years of age will be considered post-menopausal if they have been amenorrhoeic for 12 months or more following cessation of all hormonal replacement therapy and/or if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution. b) Women ≥50 years of age will be considered post-menopausal if they have been amenorrhoeic for 12 months or more following cessation of all hormonal replacement therapy or had radiation-induced menopause with most recent menses >1 year ago or had chemotherapy-induced menopause with most recent menses >1 year ago.19In the opinion of the INV, the patient must be able to understand, must be willing to sign informed consent form (ICF) and comply with all study-related procedures, medication use, and evaluations.20Patients must have 1-2 prior lines of systemic XXX therapy and have not progressed within 182 days after the date of the last dose of XXX.21Prior treatment with PARPi is required (for patients who were previously documented to be HRD positive or have a germline or somatic BRCA 1/2 mutation), if PARPi therapy was locally approved at the time of testing.
Exclusion criteria
- Patients with clear-cell, mucinous histology, mixed histology with mucinous component, sarcoma, sarcomatous component, or low-grade ovarian cancer.2Patients with XXX refractory OC (XXX refractory is defined as disease that has not responded to a primary XXX-based regimen or progressed within 30 days after primary XXX-based therapy) or XXX resistant ovarian cancer.3Patient pregnant, lactating or breastfeeding or having a positive serum pregnancy test during the screening period.4Previous systemic topoisomerase-1 inhibitor treatment (except Topotecan).5History of hypersensitivity to exatecan or excipients of the TUB-040 formulation.6Patients with unresolved malignant bowel obstruction (including patients with radiological findings indicating possible bowel obstruction on CT scans), history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess or patients on total parenteral nutrition (TPN).7Prior thoracocentesis for therapeutic drainage of malignant effusion < 4 weeks from trial inclusion and repeated paracentesis for therapeutic drainage of malignant effusion < 4 weeks before trial inclusion.8Prior radiotherapy to the pelvis or abdomen (Dose Escalation phase only).9Patients with serum albumin level < 2.5 g/dL (subjects should not have received IV albumin within 4 weeks of the test).10Participation in interventional clinical studies either concurrently or within the previous 28 days or within 5 half-lives (whichever is shorter) of any investigational pharmacologic agents before study treatment.11Patients with untreated spinal cord compression or cerebrovascular accident/stroke within < 6 months of enrollment.12Major surgery within 21 days prior to signing the ICF, unless the patient is recovered at that time.13History of non-infectious ILD/pneumonitis/radiation pneumonitis that required steroids or has current ILD/pneumonitis.14Documented cardiac comorbidities: Corrected QT interval > 470 msec on the screening ECG, unstable or uncontrolled pectoral angina, myocardial infarction during the last 6 months, valvular heart disease that requires treatment, uncontrollable hypertension (≥Grade 3), uncontrollable arrhythmias, acute myocarditis, or congestive heart failure (CHF) (New York Heart Association III or IV).15Active, uncontrolled or severe impairment of the urogenital, renal, hepatobiliary (including liver cirrhosis), cardiovascular, respiratory, gastrointestinal, neurologic, or hematopoietic systems which, in the opinion of the INV, would predispose the patient to the development of complications from the administration of protocol therapy.16Demyelinating diseases: History of multiple sclerosis or of progressive multifocal leukoencephalopathy.17History of another malignancy with ongoing treatment or not yet free from disease for 2 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or other malignancy with a similar expected curative outcome.18Any concurrent anti-cancer chemotherapy, radiotherapy (except for local radiation therapy of lesions that may cause imminent complications), hormonal therapy, immunotherapy, or corticosteroid therapy, other than that permitted in Section 8.8 in protocol.19Live vaccines within 30 days prior to study entry or any known unresolved and active bacterial, viral (e.g. Hep B, Hep C, Varicella or CMV), fungal, mycobacterial, or other infection at screening.20History of hypersensitivity to XXX and risk of further cumulative toxicity with additional XXX, including but not limited to myelosuppression, with febrile neutropenia, Grade 4 hematotoxicity, neuropathy Grade ≥2, renal insufficiency during prior XXX-based therapy.21Non-healing wounds, ulcers, or bone fractures.22History of posterior reversible encephalopathy syndrome.23Recent history of hemoptysis of ≥1/2 teaspoon of red blood within 4 weeks before first study treatment.24History of Grade 4 thromboembolic events.25Hypertension ≥ Grade 3 that is not controlled with medical management.26Clinically significant proteinuria: urine-protein (UPC) ratio ≥ 1.0 or urine dipstick result ≥ 2+; patients with UPC ratio ≥ 1.0 or ≥ 2+ proteinuria should undergo 24-hour urine collection and must show result < 1 gram of protein in 24-hour period.27Any patient who is required to take strong CYP3A4 inhibitors or inducers (see also Prohibited Medication and Guidance for Potential Use section).
Clinical Study Information for Healthcare Providers
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Study Locations
Location
Investigator
Status
Condition(s) Treated at Site
Location
START Los Angeles
Los Angeles, CA, United States, 90025
Investigator
Navid Hafez
Status
Will Be Recruiting
Condition(s) Treated at Site
Ovarian
Fallopian Tube
Primary Peritoneal
Location
START New Jersey
East Brunswick, NJ, United States, 08816
Investigator
Bruno Fang
Status
Will Be Recruiting
Condition(s) Treated at Site
Ovarian
Fallopian Tube
Primary Peritoneal
Location
START New York (Long Island)
Lake Success, NY, United States, 11042
Investigator
Geraldine O'Sullivan Coyne
Status
Will Be Recruiting
Condition(s) Treated at Site
Ovarian
Fallopian Tube
Primary Peritoneal