Durvalumab and cediranib for patients with uveal melanoma and metastasis
- Conditions
- Metastatic uveal melanomaMedDRA version: 21.1 Level: PT Classification code 10081431 Term: Uveal melanoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-001045-40-ES
- Lead Sponsor
- Grupo Español Multidisciplinar de Melanoma
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 18
1. Patients must have histologically confirmed metastatic uveal melanoma with measurable disease not eligible for curative therapy.
2. 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.
3. Patients can have received one prior therapy for metastatic disease, excepting for treatments listed in exclusion criteria.
4. Patients must be 18 years of age or older at time of study entry.
5. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
6. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations not performed according to normal practice. Patient must consent for liver metastasis biopsies donation at day 0 and day +42 since treatment initiation.
7. Adequate normal organ and marrow function as defined below: Haemoglobin >=9.0 g/dL, Absolute neutrophil count (ANC) >1.5 x 10 x9/L (> 1500 per mm3), Platelet count = 100 x 10 x9/L (>75,000 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 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.
8. 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 ran
1. Concomitant malignancy other than non-melanoma skin cancer, or superficial bladder cancer controlled with local treatment (tx).
2. Previous anti-angiogenic agents and MEK, BRAF, ERK inhibitors.
3. Previous anti-PD1/PDL1 (including durvalumab).
4. Presence of brain or leptomeningeal involvement unless previously tx, off steroids at least 2 weeks, and considered stable. Patients with untreated central nervous system metastases and/or carcinomatous meningitis either at baseline/during screening period or prior to signing the ICF. Patients with previously treated brain metastases (BM) should show radiographic stability, with any unresolved or unstable neurologic BM-related symptoms without steroids tx, or with stable dose of <=10mg/day of prednisone (or equivalent) and anticonvulsants, for >=14 days prior to the start of study tx. The BM will not be recorded as target lesions at baseline.
5. Patients < 30kg.
6. Participation in another clinical study (CS) with an investigational product during the last 4 weeks.
7. Concurrent enrolment in another interventional CS or on follow-up for interventional.
8. Last dose of anticancer tx within <=28 days prior to the first dose of study tx.
9. Any unresolved toxicity NCI CTCAE G >=2 from previous anticancer tx except for alopecia, vitiligo, and lab values defined in the inclusion criteria.
10. Any concurrent chemotx, IMP, biologic, or hormonal cancer tx different to cediranib and/or durvalumab.
11. Radiotherapy to >30% of the bone marrow or with a wide field of radiation, within 4 weeks of the first dose of study tx.
12. Major surgery within a minimum of 2 weeks prior to inclusion; patients must have recovered from any effects of any major surgery prior to inclusion.
13. History of allogeneic organ transplantation.
14. Active or prior documented autoimmune or inflammatory disorders.
15. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, compromise cediranib absorption, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
16. History of another primary malignancy except for malignancy treated with curative intent and with no known active disease >=5 years before the first dose of IMP and of low potential risk for recurrence; non-melanoma skin cancer, lentigo maligna or carcinoma in situ, all adequately treated and without evidence of disease.
17. Active primary immunodeficiency.
18. Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus.
19. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab.
20. Receipt of live attenuated vaccine within 30 days prior to the first dose of IMP.
21. Pregnant or breastfeeding female, or male/female with reproductive potential not willing
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method