Metastatic Cancer, Uveal Melanoma
Conditions
Keywords
uveal melanoma, cediranib, durvalumab, liver metastasis
Brief summary
Phase II clinical trial aimed to evaluate the efficacy of the combination of cediranib and durvalumab in patients with metastatic uveal melanoma (mUM) with biopsiable disease at first line of after failure to first line systemic or liver directed therapy.
Interventions
DRUGCediranib Maleate
Cediranib 20mg, oral, 5 days on and 2 days off until disease progression
DRUGDurvalumab
Durvalumab 1500mg, intravenous, every 4 weeks until disease progression
Sponsors
MFAR
Grupo Español Multidisciplinar de Melanoma
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have histologically confirmed metastatic uveal melanoma with measurable disease not eligible for curative therapy. * Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm with spiral CT scan, MRI, or calipers by clinical exam. Patients must have at least 1 biopsiable liver metastasis. * Patients can have received one prior therapy for metastatic disease, excepting for treatments listed in
Exclusion criteria
. * Patients must be 18 years of age or older at time of study entry. * Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1. * Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol. * Adequate normal organ and marrow function as defined below: Haemoglobin ≥9.0 g/dL, Absolute neutrophil count (ANC) \> 1.5 x 109/L (\> 1500 per mm3), Platelet count ≥ 100 x 109/L (\>100,000 per mm3). Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with Coordinating Investigator. Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \<2.5 x upper limit of normal (ULN) in the absence of liver metastases. If liver metastases are present, both AST and ALT must be no more than 5 x ULN. Creatinine clearance \>30 ml/min calculated by Cockcroft-Gault or another validated method. Urine protein:creatinine ratio (UPC) ≤1 or ≤2+ proteinuria on 2 consecutive dipsticks taken no less than 1 week apart. Subjects with 2+ proteinuria on dipstick must also have UPC \< 0.5 on 2 consecutive samples. * Postmenopausal or evidence of non-childbearing status for women of childbearing potential as confirmed by a negative urine or serum pregnancy test within 7 days prior to inclusion. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: Amenorrheic for ≥1 year in the absence of chemotherapy and/or hormonal treatments. Luteinizing hormone (LH) and/or follicle stimulating hormone and/or estradiol levels in the post-menopausal range. Radiation induced oophorectomy with last menses \>1 year ago. Chemotherapy induced menopause with \>1 year interval since last menses. Surgical sterilization (bilateral oophorectomy or hysterectomy) Women \<50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy). Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \>1 year ago, had chemotherapy-induced menopause with last menses \>1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy). * Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up. * Must have a life expectancy of at least 12 weeks * Subjects must be able to swallow and retain oral medications and be without clinically significant gastrointestinal illnesses that would preclude absorption of cediranib. * Adequately controlled BP: Systolic BP ≤140 mmHg and diastolic BP ≤90 mmHg in the presence or absence of a stable regimen of antihypertensive therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate by RECIST 1.1 | 24 months after start of treatment | ORR calculated as the proportion of patient with a complete response (CR) or partial response (PR). The final statistical analysis of this endpoint is expected to be performed every 8 weeks since start of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival Rate at 12 months | 12 months after start of treatment | Proportion of patients alive 12 months since start of treatment |
| Overall Survival Rate at 24 months | 24 months after start of treatment | Proportion of patients alive 24 months since start of treatment |
| Increase in effector CD8 T-cell response in the tumor induced by cediranib combined with durvalumab | 24 months after start of treatment | Changes in the CD8 values from baseline |
| Median Progression-free survival (PFS) by RECIST 1.1 | 24 months after start of treatment | Median time between start of treatment and date of progression of disease |
| Number of participants with serious adverse events as assessed by CTCAE v5.0 | 24 months | — |
| Number of participants with immune-related adverse events as assessed by CTCAE v5.0 | 24 months | — |
| Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 | 24 months | — |
| Number of participants with adverse events as assessed by CTCAE v5.0 | 24 months | — |
Countries
Spain
Outcome results
None listed