Clinical trial
Phase I/II, Open-Label Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of Durvalumab Monotherapy or in Combination With Tremelimumab in Pediatric Patients With Advanced Solid Tumors and Hematological Malignancies.
Name
D419EC00001
Description
The purpose of the study is to determine the recommended dose of durvalumab and tremelimumab (immunotherapy drugs) in pediatric patients with advanced solid and hematological cancers and expand in a second phase to test the efficacy of these drugs once this dose is determined.
Trial arms
Trial start
2019-03-07
Estimated PCD
2023-02-28
Trial end
2024-12-30
Status
Active (not recruiting)
Phase
Early phase I
Treatment
Durvalumab / Tremelimumab Combination Therapy
Starting dose:
durvalumab: 20mg/kg tremelimumab: 1mg/kg at cycles 2 to 5 only co-administered with durvalumab. The Recommended Phase 2 dose will be used for the dose expansion phase.
Arms:
Durvalumab / Tremelimumab Combination Therapy
Other names:
durvalumab: Imfinzi, MEDI4736, tremelimumab: CP-675,206
Size
56
Primary endpoint
Dose-Finding Phase: Maximum Serum Concentration (Cmax) of Durvalumab
Pre-infusion and post-infusion on Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, pre-infusion and post-infusion on Cycle 2 Day 1, pre-infusion and post-infusion in Cycle 3, 4, 6, 8, 10 and 12
Dose-Finding Phase: Minimum Serum Concentration (Cmin) of Durvalumab
Pre-infusion and post-infusion on Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, pre-infusion and post-infusion on Cycle 2 Day 1, pre-infusion and post-infusion in Cycle 3, 4, 6, 8, 10 and 12
Dose-Finding Phase: Area Under the Serum Concentration-Time Curve (AUC) From Zero to 14 (AUC 0-14) of Durvalumab
Pre-infusion and post-infusion on Cycle 1 Day 1 and Cycle 1 Day 8
Dose-Finding Phase: AUC From Zero to 28 (AUC 0-28) of Durvalumab
Pre-infusion and post-infusion on Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 1 Day 15
Dose-Finding Phase: Time to Cmax (Tmax) of Durvalumab
Pre-infusion and post-infusion on Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, pre-infusion and post-infusion on Cycle 2 Day 1, pre-infusion and post-infusion in Cycle 3, 4, 6, 8, 10 and 12
Dose-Finding Phase: Apparent Terminal Elimination Half-life Associated With the Terminal Slope of the Semi-logarithmic Concentration Time Curve (t½λz) of Durvalumab
Pre-infusion and post-infusion on Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, pre-infusion and post-infusion on Cycle 2 Day 1, pre-infusion and post-infusion in Cycle 3, 4, 6, 8, 10 and 12
Dose-Finding Phase: Dose-Normalized AUC (0-14) (AUC [0-14]/D) of Durvalumab
Pre-infusion and post-infusion on Cycle 1 Day 1 and Cycle 1 Day 8
Dose-Finding Phase: Dose-Normalized AUC (0-28) (AUC [0-28]/D) of Durvalumab
Pre-infusion and post-infusion on Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 1 Day 15
Dose-Finding Phase: Dose-Normalized Cmax (Cmax/D) of Durvalumab
Pre-infusion and post-infusion on Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, pre-infusion and post-infusion on Cycle 2 Day 1, pre-infusion and post-infusion in Cycle 3, 4, 6, 8, 10 and 12
Dose-Finding Phase: Cmax of Tremelimumab
Pre-infusion and post-infusion on Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15, pre-infusion and post-infusion in Cycle 3, 4, and 5
Dose-Finding Phase: Cmin of Tremelimumab
Pre-infusion and post-infusion on Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15, pre-infusion and post-infusion in Cycle 3, 4, and 5
Dose-Finding Phase: (AUC 0-14) of Tremelimumab
Pre-infusion and post-infusion on Cycle 2 Day 1, and Cycle 2 Day 8
Dose-Finding Phase: (AUC 0-28) of Tremelimumab
Pre-infusion and post-infusion on Cycle 2 Day 1, Cycle 2 Day 8, and Cycle 2 Day 15
Dose-Finding Phase: Tmax of Tremelimumab
Pre-infusion and post-infusion on Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15, pre-infusion and post-infusion in Cycle 3, 4, and 5
Dose-Finding Phase: T½λz of Tremelimumab
Pre-infusion and post-infusion on Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15, pre-infusion and post-infusion in Cycle 3, 4, and 5
Dose-Finding Phase: AUC (0-14)/D of Tremelimumab
Pre-infusion and post-infusion on Cycle 2 Day 1 and Cycle 2 Day 8
Dose-Finding Phase: AUC (0-28)/D of Tremelimumab
Pre-infusion and post-infusion on Cycle 2 Day 1, Cycle 2 Day 8, and Cycle 2 Day 15
Dose-Finding Phase: Cmax/D of Tremelimumab
Pre-infusion and post-infusion on Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15, pre-infusion and post-infusion in Cycle 3, 4, and 5
Dose-Finding Phase: Number of Participants With Adverse Events (AE), Serious AE (SAE), AE Leading to Discontinuation of Durvalumab and Tremelimumab, AE of Special Interest (AESI) or AE of Possible Interest (AEPI) Related to Durvalumab and Tremelimumab
From Day 1 up to 15 months
Dose-Expansion Phase Only: Objective Response Rate (ORR)
From first dose of study treatment until death or up to approximately 4 years (clinical DCO of 20 Apr 2023)
Dose-Expansion Phase Only: Duration of Response (DOR)
From first dose of study treatment until death or up to approximately 4 years (clinical DCO of 20 Apr 2023)
Dose-Expansion Phase Only: Best Objective Response (BOR)
From first dose of study treatment until death or up to approximately 4 years (clinical DCO of 20 Apr 2023)
Dose-Expansion Phase Only: Disease Control Rate (DCR)
At 16 and 24 Weeks
Dose-Expansion Phase Only: PFS
From first dose of study treatment until death or up to approximately 4 years (clinical DCO of 20 Apr 2023)
Dose-Expansion Phase Only: Overall Survival (OS)
From first dose of study treatment until death or up to approximately 4 years (clinical DCO of 20 Apr 2023)
Dose-Expansion Phase Only: Survival Rate at 12 Months and 24 Months
At 12 and 24 Weeks
Eligibility criteria
Inclusion Criteria:
* Max Age =17 years
* Solid Tumors (except primary central nervous system malignant tumors): Patients must have a histopathologic confirmation of malignancy. Patients must have progressed or are refractory to standard therapies, and for whom no standard of care treatments exist
* Non-Hodgkin's Lymphoma, limited to primary mediastinal B-cell lymphoma and anaplastic large cell lymphoma. Patients must have progressed or are refractory to standard therapies, and for whom no standard of care treatments exist.
* Provision of diagnostic tumor sample mandated if available
* Evaluable disease
* No prior exposure to immune-mediated therapy
* Adequate organ and marrow function
* Life expectancy of at least 3 months
Exclusion Criteria:
* History of allogeneic organ transplantation (exceptions may be allowed for NHL after discussion with Sponsor). History of autologous bone marrow transplant may be allowed (after discussion with Sponsor).
* Active or prior documented autoimmune or inflammatory disorders (exceptions)
* Uncontrolled intercurrent illness
* History of primary immunodeficiency
* Active infection including tuberculosis, hepatitis B, C or HIV
* Any unresolved toxicity NCI CTCAE version 5.0 Grade ≥2 from previous anticancer therapy (exceptions)
Protocol
{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1', 'PHASE2'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 56, 'type': 'ACTUAL'}}
Updated at
2024-03-19
1 organization
1 product
3 indications
Organization
AstraZenecaProduct
Durvalumab + TremelimumabIndication
Pediatric CancerIndication
Pediatric Solid TumorIndication
Hematological Malignancies