Durvalumab (MEDI4736) Plus Cediranib in Patients With Metastatic Uveal Melanoma

NCT04184518 | Withdrawn Phase 2 DMC

• 3 other identifiers: GEM-1805ESR-18-140022019-001045-40
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 5

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.

Conditions

Uveal Melanoma; Metastatic Cancer

Keywords

uveal melanoma; cediranib; durvalumab; liver metastasis

Outcome Measures

Primary Outcomes (1)

• Objective response rate by RECIST 1.1

  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.

  24 months after start of treatment

Secondary Outcomes (8)

• Median Progression-free survival (PFS) by RECIST 1.1

  24 months after start of treatment

• Overall Survival Rate at 12 months

  12 months after start of treatment

• Overall Survival Rate at 24 months

  24 months after 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

• Number of participants with adverse events as assessed by CTCAE v5.0

  24 months

Study Arms (1)

Cediranib plus durvalumab

EXPERIMENTAL

Drug: Cediranib Maleate; Drug: Durvalumab

Interventions

Cediranib Maleate DRUG

Cediranib 20mg, oral, 5 days on and 2 days off until disease progression

Cediranib plus durvalumab

Durvalumab DRUG

Durvalumab 1500mg, intravenous, every 4 weeks until disease progression

Also known as: MEDI4736

Cediranib plus durvalumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.
• Patients with concomitant malignancy other than non-melanoma skin cancer, or superficial bladder cancer controlled with local treatment.
• Previous treatment with anti-angiogenic agents MEK, BRAF, ERK inhibitors.
• Previous treatment with anti-PD1/PDL1 (including durvalumab) treatments.
• Presence of brain or leptomeningeal involvement unless previously treated, off steroids at least 2 weeks, and considered stable. Patients with untreated central nervous system (CNS) metastases and/or carcinomatous meningitis identified either on the baseline brain imaging \[RECIST\]) obtained during the screening period or identified prior to signing the ICF. Patients whose brain metastases have been treated may participate provided they show radiographic stability (defined as 2 brain images, both of which are obtained after treatment to the brain metastases. These imaging scans should both be obtained at least four weeks apart and show no evidence of intracranial progression). In addition, any neurologic symptoms that developed either as a result of the brain metastases or their treatment must have resolved or be stable either, without the use of steroids, or are stable on a steroid dose of ≤10mg/day of prednisone or its equivalent and anticonvulsants, for at least 14 days prior to the start of treatment. Brain metastases will not be recorded as RECIST Target Lesions at baseline.
• Patients weighing \<30kg will be excluded from enrollment.
• Participation in another clinical study with an investigational product during the last 4 weeks.
• Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.

Sponsors & Collaborators

• Grupo Español Multidisciplinar de Melanoma: lead
• MFAR: collaborator

Study Sites (5)

Instituto Catalá d'Oncología L'Hospitalet

L'Hospitalet de Llobregat, Barcelona, Spain

Location

H. U. Virgen de la Victoria

Málaga, Spain

Location

Clínica Universidad de Navarra

Pamplona, Spain

Location

H.U. Virgen Macarena

Seville, Spain

Location

Hospital General Universitario de Valencia

Valencia, Spain

Location

MeSH Terms

Conditions

Uveal Melanoma; Neoplasm Metastasis

Interventions

cediranib; durvalumab

Condition Hierarchy (Ancestors)

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• José M. Piulats

  Institut Català d'Oncología L'Hospitalet

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2019
• First Posted: December 3, 2019
• Study Start: May 1, 2020
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2021
• Last Updated: June 2, 2020

Record last verified: 2020-05

Locations

ES (5)