Study of NUC-1031 for the treatment of platinum-resistant ovarian cancer

Phase 1

• Conditions: Platinum-resistant epithelial cancer of the ovary, fallopian tube or primary peritoneum (here termed ‘ovarian cancer’), who have been treated with 3 or more prior chemotherapy regimens.; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-003287-39-GB
• Lead Sponsor: uCana plc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2017-03-22
• Study Completion: 2019-12-31
• Last Update Posted: 9 September 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 53

Inclusion Criteria

1. Provision of signed written informed consent. Patients with easily accessible tumour must also consent to the collection of fresh biopsy tumour tissue to participate in the study. Patients who do not have easily accessible tumour for biopsy should not be put at undue risk for sample collection and these patients remain eligible for the study.
2. Original diagnosis and/or histological confirmation of high-grade serous, high-grade endometrioid, undifferentiated/unclassifiable epithelial ovarian, fallopian tube or primary peritoneal cancer.
3. Platinum-free interval since last line of platinum of less than 6 months (182 days).
4. Received at least 3 prior chemotherapy-containing regimens. Prior treatment with only non-cytotoxic agents (e.g. hormones, antibodies or PARP inhibitors) is permitted, but should not be considered as one of the ‘3 prior chemotherapy-containing regimens’. Adjuvant chemotherapy should be counted as a prior line of chemotherapy.
5. Age =18 years.
6. ECOG performance status of 0 or 1.
7. Measurable disease as defined by RECIST.
8. Adequate bone marrow function as defined by: absolute neutrophil count (ANC) =1.5×10^9/l, platelet count =100×10^9/l and hemoglobin level =10.0 g/dl.
9. Adequate liver function, as defined by: serum total bilirubin =1.5×upper limit of normal (ULN), AST and ALT =2.5×ULN (or =5×ULN if liver metastases are present).
10. Adequate renal function assessed as Cr <1.5×ULN or GFR =50 ml/min.
11. Ability to comply with protocol requirements.
12. Patients are assumed to be infertile as a consequence of treatment for their disease, however, in the event they are not, patients must be postmenopausal (12 months of amenorrhea), agree to be abstinent, or they must agree to use two forms of contraception, one of which must be a barrier method and the other must be a highly effective method. These forms of contraception must be used from the time of signing consent, throughout the treatment period, and for 30 days following the last NUC-1031 dose administration. Oral or injectable contraceptive agents cannot be the sole method of contraception. See protocol Section 10.3.1 for more information. Patients of childbearing potential must have a negative serum pregnancy test within 72 hours prior to the first study drug administration. This criterion does not apply to patients who have had a previous hysterectomy or bilateral oophorectomy.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 14

Exclusion Criteria

1. Disease classified as primary platinum refractory (i.e. progression while receiving initial line of platinum-based therapy or within 4 weeks of the last platinum dose of the initial regimen).
2. Received fewer than 3 prior chemotherapy-containing regimens.
3. Prior therapy with single-agent gemcitabine (prior gemcitabine plus carboplatin combination treatment is permitted).
4. Prior history of hypersensitivity to gemcitabine.
5. History of allergic reactions attributed to the components of the diluents used with NUC-1031.
6. Mucinous, low-grade serous, low-grade endometrioid, carcinosarcoma, clear cell or undifferentiated/unclassifiable histology.
7. Symptomatic CNS or leptomeningeal metastases.
8. Prior chemotherapy, radiotherapy (other than short cycle of palliative radiotherapy for bone pain), treatment with a VEGF inhibitor, PARP inhibitor or immunotherapy within 21 days of first receipt of study drug (within 6 weeks for nitrosoureas and mitomycin C); hormone therapy within 14 days of first receipt of study drug; or blood transfusion, or use of hematopoietic growth factors within 28 days of first receipt of study drug.
9. Residual toxicities from chemotherapy or radiotherapy, which have not regressed to Grade =1 severity (NCI CTCAE v4), except for neuropathy (Grade 2 allowed) or alopecia.
10. Patients who have a history of another malignancy diagnosed within the past 5 years, with the exception of adequately treated non-melanoma skin cancer curatively treated carcinoma in situ of the cervix or ductal carcinoma in situ (DCIS) of the breast. Patients with previous invasive cancers are eligible if treatment was completed more than 5 years prior to initiating the current study treatment, and the patient has had no evidence of recurrence since then.
11. Presence of an uncontrolled concomitant illness or active infection requiring IV antibiotics.
12. Presence of any serious illnesses, medical conditions, or other medical history, including laboratory results, which, in the Investigator’s opinion, would be likely to interfere with the patient's participation in the study, or with the interpretation of the results.
13. Known HIV positive or known active hepatitis B or C.
14. Any condition (e.g. known or suspected poor compliance, psychological instability, geographical location, etc.) that, in the judgment of the Investigator, may affect the patient’s ability to sign the informed consent and undergo study procedures.
15. Currently pregnant, lactating or breastfeeding.
16. QTc interval >450 milliseconds.
17. Concomitant use of drugs known to prolong QT/QTc interval.
18. History of radiologically confirmed bowel obstruction (including sub-occlusive disease) relating to ovarian cancer within 6 months prior to the first receipt of study drug.
19. Patients who have received a live vaccination within 4 weeks of first planned NUC-1031 dose administration.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified