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.
Title
- Brief Title: Durvalumab and Tremelimumab for Pediatric Malignancies
- Official Title: 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
Clinical Trial IDs
- ORG STUDY ID:
D419EC00001
- NCT ID:
NCT03837899
Conditions
- Pediatric Cancer
- Solid Tumor Pediatric
- Hematological Malignancies
Interventions
Drug | Synonyms | Arms |
---|
Durvalumab / Tremelimumab Combination Therapy | durvalumab: Imfinzi, MEDI4736, tremelimumab: CP-675,206 | Durvalumab / Tremelimumab Combination Therapy |
Purpose
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.
Detailed Description
This is a first time in pediatrics study primarily designed to evaluate the safety and
tolerability of durvalumab and durvalumab in combination with tremelimumab at increasing
doses in pediatric patients with advanced solid malignancies and hematological malignancies
(including lymphomas) and for whom no standard of care treatments exist. Although treatment
efficacy is not a primary objective of this study given its early phase nature, the patients
screened for this study have no curative options and this study offers the potential of some
benefit.
The study will also characterize the PK of durvalumab and durvalumab in combination with
tremelimumab in children and adolescents and explore potential biological activity and
immunogenicity by assessing pharmacodynamics, anti drug antibody (ADA) levels, and anti-tumor
activity. The results from this trial will form the basis for decisions for potential future
pediatric studies.
Trial Arms
Name | Type | Description | Interventions |
---|
Durvalumab / Tremelimumab Combination Therapy | Experimental | Part 1 (dose finding) Durvalumab + tremelimumab Combination Treatment. Durvalumab and tremelimumab are initially administered at dose level 1 and dose escalated based on results from PK modeling and tolerance to determine the RP2D. Both drugs are administered every 4 weeks as intravenous infusions. Tremelimumab is only administered with durvavalumab for 4 doses, from cycles 2-5. (sarcoma, NB and NHL)
Part 2 (dose expansion phase) Durvalumab + tremelimumab Combination Treatment. Durvalumab and tremelimumab are administered at the RP2D, every 4 weeks as intravenous infusions. Tremelimumab is only administered with durvalumab for 4 doses, from cycles 1-4. Tremelimumab may be added for 4 doses at time of progressive disease. Cohorts: solid tumors, sarcomas, NHL restricted to PMBCL and ALCL subtypes) | - Durvalumab / Tremelimumab Combination Therapy
|
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)
Maximum Eligible Age: | 18 Years |
Minimum Eligible Age: | N/A |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Dose Finding phase: Recommended Phase 2 Dose |
Time Frame: | 15 months |
Safety Issue: | |
Description: | Endpoints include adult equivalent dose for both durvalumab (administered as monotherapy and in combination) and for tremelimumab, to reflect the RP2D regimen dose for durvalumab monotherapy and for the combination treatment |
Secondary Outcome Measures
Measure: | Pharmacokinetics (PK) of Durvalumab and Tremelimumab |
Time Frame: | 15 months. |
Safety Issue: | |
Description: | Serum concentrations of Durvalumab and Tremelimumab |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | AstraZeneca |
Trial Keywords
- Pediatric, solid tumors, hematological malignancies, durvalumab, tremelimumab, immunotherapy
Last Updated
August 3, 2021