Ovarian Cancer
Conditions
Keywords
Platinum-resistant, ovarian neoplasm, antineoplastic agents, ovarian diseases, cancer of the ovary
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.
Interventions
DRUGNUC-1031 500 mg
NUC-1031 500 mg/m2 on Days 1, 8, and 15 of a 28-day cycle.
DRUGNUC-1031 750mg
NUC-1031 750 mg/m2 on Days 1, 8, and 15 of a 28-day cycle
Sponsors
NuCana plc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response | Assessed from date of randomization until disease progression, up to end of the study (approximately 2 years) | 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. |
Countries
United Kingdom, United States
Participant flow
Recruitment details
A total of 87 patients were screened, of whom 53 patients were randomized and 51 patients received at least one dose of NUC-1031. These 51 patients were included in the full analysis set and the safety analysis set.
Pre-assignment details
Screening details: Patients with histologically-confirmed platinum-resistant high-grade serious, high-grade endometrioid, epithelial cancer of the ovary, fallopian tube or primary peritoneum (here termed 'ovarian cancer'), who had been treated with 3 or more prior chemotherapy regimens were eligible. The Screening visit was to occur within 28 days of Cycle 1 Day 1.
Participants by arm
| Arm | Count |
|---|---|
| Arm A NUC-1031 500 mg/m2 administered on Days 1, 8, and 15 of 28-day cycles | 25 |
| Arm B NUC-1031 750 mg/m2 administered on Days 1, 8, and 15 of 28-day cycles | 28 |
| Total | 53 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Did not receive study treatment | 1 | 1 |
Baseline characteristics
| Characteristic | Arm A | Arm B | Total |
|---|---|---|---|
| Age, Customized 55 - <66 years | 6 Participants | 10 Participants | 16 Participants |
| Age, Customized <55 years | 6 Participants | 4 Participants | 10 Participants |
| Age, Customized 66 - 75 years | 9 Participants | 10 Participants | 19 Participants |
| Age, Customized >75 years | 4 Participants | 4 Participants | 8 Participants |
| Comorbidity at baseline No | 6 Participants | 9 Participants | 15 Participants |
| Comorbidity at baseline Yes | 19 Participants | 19 Participants | 38 Participants |
| Documented deleterious BRCA mutation No | 21 Participants | 23 Participants | 44 Participants |
| Documented deleterious BRCA mutation Unknown | 0 Participants | 1 Participants | 1 Participants |
| Documented deleterious BRCA mutation Yes | 4 Participants | 4 Participants | 8 Participants |
| Eastern Cooperative Oncology Group (ECOG) performance status 0 | 8 Participants | 12 Participants | 20 Participants |
| Eastern Cooperative Oncology Group (ECOG) performance status 1 | 16 Participants | 16 Participants | 32 Participants |
| Eastern Cooperative Oncology Group (ECOG) performance status Unknown | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 28 Participants | 52 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Histology High grade endometroid | 1 Participants | 1 Participants | 2 Participants |
| Histology High grade serous | 24 Participants | 23 Participants | 47 Participants |
| Histology Not recorded | 0 Participants | 1 Participants | 1 Participants |
| Histology Other | 0 Participants | 3 Participants | 3 Participants |
| Metastatic disease No | 0 Participants | 1 Participants | 1 Participants |
| Metastatic disease Not recorded | 0 Participants | 1 Participants | 1 Participants |
| Metastatic disease Yes | 25 Participants | 26 Participants | 51 Participants |
| Number of prior lines of therapy | 4.5 Therapies | 5.0 Therapies | 4.8 Therapies |
| Original diagnosis Fallopian tube | 4 Participants | 2 Participants | 6 Participants |
| Original diagnosis Not recorded | 0 Participants | 1 Participants | 1 Participants |
| Original diagnosis Other | 2 Participants | 0 Participants | 2 Participants |
| Original diagnosis Ovarian | 16 Participants | 20 Participants | 36 Participants |
| Original diagnosis Primary peritoneal | 3 Participants | 5 Participants | 8 Participants |
| Prior gemcitabine-containing regimen No | 12 Participants | 11 Participants | 23 Participants |
| Prior gemcitabine-containing regimen Yes | 13 Participants | 17 Participants | 30 Participants |
| Prior systemic cancer therapy No | 1 Participants | 1 Participants | 2 Participants |
| Prior systemic cancer therapy Yes | 24 Participants | 27 Participants | 51 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black/African American | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 23 Participants | 26 Participants | 49 Participants |
| Sex/Gender, Customized Female | 25 Participants | 28 Participants | 53 Participants |
| Stage at screening Not recorded | 0 Participants | 1 Participants | 1 Participants |
| Stage at screening Stage I | 1 Participants | 0 Participants | 1 Participants |
| Stage at screening Stage II | 1 Participants | 0 Participants | 1 Participants |
| Stage at screening Stage III | 8 Participants | 7 Participants | 15 Participants |
| Stage at screening Stage IV | 13 Participants | 18 Participants | 31 Participants |
| Stage at screening Unknown | 2 Participants | 2 Participants | 4 Participants |
| Time since initial diagnosis | 4.3 years | 5.6 years | 5.0 years |
| Time to progression after start of most recent chemotherapy >12 months | 1 Participants | 0 Participants | 1 Participants |
| Time to progression after start of most recent chemotherapy <= 1 month | 0 Participants | 0 Participants | 0 Participants |
| Time to progression after start of most recent chemotherapy >1 to 6 months | 14 Participants | 15 Participants | 29 Participants |
| Time to progression after start of most recent chemotherapy >6 to 9 months | 2 Participants | 1 Participants | 3 Participants |
| Time to progression after start of most recent chemotherapy >9 to 12 months | 1 Participants | 0 Participants | 1 Participants |
| Time to progression after start of most recent chemotherapy Missing | 7 Participants | 12 Participants | 19 Participants |
| Treatment-free interval from completion of most recent chemotherapy <= 1 month | 2 Participants | 3 Participants | 5 Participants |
| Treatment-free interval from completion of most recent chemotherapy >1 to 3 months | 14 Participants | 10 Participants | 24 Participants |
| Treatment-free interval from completion of most recent chemotherapy >3 to 6 months | 5 Participants | 9 Participants | 14 Participants |
| Treatment-free interval from completion of most recent chemotherapy >6 to 9 months | 2 Participants | 4 Participants | 6 Participants |
| Treatment-free interval from completion of most recent chemotherapy >9 months | 1 Participants | 1 Participants | 2 Participants |
| Treatment-free interval from completion of most recent chemotherapy Missing | 1 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 21 / 24 | 21 / 27 |
| other Total, other adverse events | 24 / 24 | 26 / 27 |
| serious Total, serious adverse events | 8 / 24 | 10 / 27 |
Outcome results
Primary
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.
Time frame: Assessed from date of randomization until disease progression, up to end of the study (approximately 2 years)
Population: Evaluable population are patients who received at least one dose of study treatment and who had measurable disease at baseline.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A | Best Overall Response | Complete response | 0 Participants |
| Arm A | Best Overall Response | Partial response | 2 Participants |
| Arm A | Best Overall Response | Stable disease | 8 Participants |
| Arm A | Best Overall Response | Progressive disease | 12 Participants |
| Arm A | Best Overall Response | Not evaluable | 1 Participants |
| Arm A | Best Overall Response | Missing | 1 Participants |
| Arm B | Best Overall Response | Not evaluable | 2 Participants |
| Arm B | Best Overall Response | Complete response | 1 Participants |
| Arm B | Best Overall Response | Progressive disease | 10 Participants |
| Arm B | Best Overall Response | Partial response | 0 Participants |
| Arm B | Best Overall Response | Missing | 5 Participants |
| Arm B | Best Overall Response | Stable disease | 8 Participants |
Post Hoc
Best Overall Response (in Evaluable for Response Set)
Post-hoc analysis of best overall response to study treatment, as assessed by blinded independent central review according to RECIST v1.1, in the per protocol evaluable for response set of patients. Per protocol evaluable for response set is defined as all patients from the Full Analysis Set who had measurable disease at baseline, at least one post-baseline scan and who received a dose of NUC-1031 on all dosing days of Cycle 1.
Time frame: Assessed from date of randomization until disease progression, up to end of the study (approximately 2 years)
Population: Reporting group
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A | Best Overall Response (in Evaluable for Response Set) | Partial response | 2 Participants |
| Arm A | Best Overall Response (in Evaluable for Response Set) | Progressive disease | 8 Participants |
| Arm A | Best Overall Response (in Evaluable for Response Set) | Stable disease | 6 Participants |
| Arm A | Best Overall Response (in Evaluable for Response Set) | Not evaluable | 1 Participants |
| Arm A | Best Overall Response (in Evaluable for Response Set) | Complete response | 0 Participants |
| Arm B | Best Overall Response (in Evaluable for Response Set) | Not evaluable | 0 Participants |
| Arm B | Best Overall Response (in Evaluable for Response Set) | Complete response | 1 Participants |
| Arm B | Best Overall Response (in Evaluable for Response Set) | Partial response | 0 Participants |
| Arm B | Best Overall Response (in Evaluable for Response Set) | Stable disease | 1 Participants |
| Arm B | Best Overall Response (in Evaluable for Response Set) | Progressive disease | 3 Participants |