NUC-1031 in Patients With Platinum-Resistant Ovarian Cancer

Study Overview
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Brief Summary
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This study was designed to evaluate the effect of two dose levels of NUC-1031 (500 mg/m2 and 750mg/m2) in patients with ovarian cancer. The primary objective was to determine the anti-tumor activity of NUC-1031 at the selected dose level (500 mg/m2 or 750 mg/m2).

Detailed Description
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A total of 53 patients were randomized, of whom 51 patients were treated in Part I of the study, 24 patients in the 500 mg/m2 arm and 27 patients in the 750 mg/m2 arm. Eligible, consenting patients received NUC-1031 by IV infusion on Days 1, 8, and 15 of each 28-day cycle. Patients continued to receive NUC-1031 until the occurrence of disease progression and underwent imaging every 8 weeks. After disease progression, patients were followed for overall survival. Part II of the study was designed to select one of the treatment dose levels for further evaluation based on clinical and laboratory assessments of patients recruited in Part I. Despite promising efficacy and a good tolerability profile in Part I, it was decided not to initiate Part II as the pre-specified boundary for efficacy was uncertain to be met in this heavily pre-treated population with significant co-morbidities.

Official Title
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A Phase II Open-Label Study of NUC-1031 in Patients With Platinum-Resistant Ovarian Cancer

Conditions
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Ovarian Cancer

Intervention / Treatment
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* Drug: NUC-1031 500 mg
* Drug: NUC-1031 750mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of signed written informed consent. Original diagnosis and/or histological confirmation of high-grade serous, high-grade endometrioid, undifferentiated/unclassifiable epithelial ovarian, fallopian tube or primary peritoneal cancer. Time from the last line of platinum-based chemotherapy of less than 6 months. Received at least 3 prior chemotherapy-containing regimens. Age ≥18 years. Ability to comply with protocol requirements. Patients are not of childbearing potential or they must agree to use a physical method of contraception. Exclusion Criteria: Disease that progressed while receiving initial line of platinum-based chemotherapy. Received fewer than 3 prior chemotherapy-containing regimens. Prior therapy with single-agent gemcitabine. Prior history of hypersensitivity to gemcitabine. Prior chemotherapy, radiation (other than short cycle of radiation to reduce bone pain), treatment with a VEGF inhibitor, PARP inhibitor or immunotherapy within 21 days of first receipt of study drug. Hormone therapy within 14 days of first receipt of study drug. Residual side effects from chemotherapy or radiation, which have not gotten better except for nerve pain or tingling or hair loss. Patients who have a history of another type of cancer diagnosed within the past 5 years, with the exception of adequately treated non-melanoma skin cancer curatively treated cervical cancer or ductal carcinoma in situ (DCIS) of the breast. Presence of an serious illness, uncontrolled illness, or active infection requiring IV antibiotics. Presence of any serious illnesses, serious medical conditions, serious medical history, active bacterial or viral infections including hepatitis B or C, or known to be HIV positive. Currently pregnant, lactating or breastfeeding. History of blocked intestines because of ovarian cancer, unless fully resolved.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>NUC-1031 500 mg/m2 administered on Days 1, 8, and 15 of 28-day cycles | Drug: NUC-1031 500 mg<br>* NUC-1031 500 mg/m2 on Days 1, 8, and 15 of a 28-day cycle.<br>* Other names: fosgemcitabine palabenamide;|
| Experimental: Arm B<br>NUC-1031 750 mg/m2 administered on Days 1, 8, and 15 of 28-day cycles | Drug: NUC-1031 750mg<br>* NUC-1031 750 mg/m2 on Days 1, 8, and 15 of a 28-day cycle<br>* Other names: fosgemcitabine palabenamide;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Overall Response | Best overall response to study treatment, as assessed by blinded independent central review according to RECIST v1.1, in the evaluable population of patients who received at least one dose of study treatment and had measurable disease at baseline. Complete Response (CR): disappearance of all target and non-target lesions, normalization of tumor markers, and pathological lymph nodes must have short axis measurements <10 mm. Partial Response (PR): ≥30% decrease in the sum of measures of target lesions, taking as reference the baseline sum of diameters. Non-target lesions must be non-progressive disease. Stable Disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest sum of diameters on study. Progressive Disease (PD): ≥20% increase in the sum of measured lesions taking as reference the smallest sum of diameters recorded on study and an absolute increase of ≥5mm. | Assessed from date of randomization until disease progression, up to end of the study (approximately 2 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Platinum-resistant, ovarian neoplasm, antineoplastic agents, ovarian diseases, cancer of the ovary