Clinical trial NCT03146663: NUC-1031 in Patients With Platinum-Resistant Ovarian Cancer
Official title: A Phase II Open-Label Study of NUC-1031 in Patients With Platinum-Resistant Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Ovarian Cancer
Keywords: Platinum-resistant
ovarian neoplasm
antineoplastic agents
ovarian diseases
cancer of the ovary
Lead sponsor: NuCana plc
Sponsor class: OTHER
First posted: 2017-05-10
Enrollment: 53
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Provision of signed written informed consent.
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. Time from the last line of platinum-based chemotherapy of less than 6 months.
4. Received at least 3 prior chemotherapy-containing regimens.
5. Age ≥18 years.
6. Ability to comply with protocol requirements.
7. Patients are not of childbearing potential or they must agree to use a physical method of contraception.

Exclusion Criteria:

1. Disease that progressed while receiving initial line of platinum-based chemotherapy.
2. Received fewer than 3 prior chemotherapy-containing regimens.
3. Prior therapy with single-agent gemcitabine.
4. Prior history of hypersensitivity to gemcitabine.
5. 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.
6. Residual side effects from chemotherapy or radiation, which have not gotten better except for nerve pain or tingling or hair loss.
7. 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.
8. Presence of an serious illness, uncontrolled illness, or active infection requiring IV antibiotics.
9. 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.
10. Currently pregnant, lactating or breastfeeding.
11. History of blocked intestines because of ovarian cancer, unless fully resolved.

Primary outcomes:
measure: Best Overall Response
timeFrame: Assessed from date of randomization until disease progression, up to end of the study (approximately 2 years)
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Arizona Oncology Associates, PC - HAL
state: Arizona
city: Tucson
country: United States
facility: Arizona Oncology Associates, PC - HOPE
state: Arizona
city: Lakewood
country: United States
facility: Rocky Mountain Cancer Centers, LLP
state: Colorado
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists and Research Institute
state: Florida
city: Edina
country: United States
facility: Minnesota Oncology Hematology, P.A.
state: Minnesota
city: Kansas City
country: United States
facility: SCRI - HCA Health Midwest
state: Missouri
city: Nashville
country: United States
facility: Nashville Tennessee Oncology
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology - South Austin
state: Texas
city: The Woodlands
country: United States
facility: Texas Oncology The Woodlands, Gynecologic Oncology
state: Texas
city: Tyler
country: United States
facility: Texas Oncology - Tyler
state: Texas
city: Edinburgh
country: United Kingdom
facility: Edinburgh Cancer Centre
city: Glasgow
country: United Kingdom
facility: Cancer Research UK Clinical Trial Unit
city: London
country: United Kingdom
facility: St Bartholomew's Hospital
city: London
country: United Kingdom
facility: University College London Hospital
city: London
country: United Kingdom
facility: Royal Marsden Hospital
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
city: Oxford
country: United Kingdom
facility: Oxford University Hospital Foundation Trust
Study officials:
affiliation: NuCana plc
name: Elisabeth Oelmann, MD PhD
role: STUDY_DIRECTOR
References: