Durvalumab and Tremelimumab for Pediatric Malignancies

Sponsor
AstraZeneca (Industry)
Overall Status
Recruiting
CT.gov ID
NCT03837899
Collaborator
(none)
158
Enrollment
23
Locations
1
Arm
57.5
Anticipated Duration (Months)
6.9
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or DiseaseIntervention/TreatmentPhase
  • Drug: Durvalumab / Tremelimumab Combination Therapy
Phase 1/Phase 2

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

Study Design

Study Type:
Interventional
Anticipated Enrollment :
158 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Mar 7, 2019
Anticipated Primary Completion Date :
Jun 23, 2023
Anticipated Study Completion Date :
Dec 22, 2023

Arms and Interventions

ArmIntervention/Treatment
Experimental: Durvalumab / Tremelimumab Combination Therapy

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)

Drug: 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.
Other Names:
  • durvalumab: Imfinzi, MEDI4736
  • tremelimumab: CP-675,206
  • Outcome Measures

    Primary Outcome Measures

    1. Dose Finding phase: Recommended Phase 2 Dose [15 months]

      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

    2. Safety and Tolerability [Up to 4 years.]

      Evaluated based on adverse events occurring throughout the study

    3. Objective Response Rate (dose expansion phase only) [up to 4 years.]

      Number (%) of patients achieving complete or partial response according to RECIST 1.1. (solid tumors) and disease-specific response criteria.

    Secondary Outcome Measures

    1. Pharmacokinetics (PK) of Durvalumab and Tremelimumab [15 months.]

      Serum concentrations of Durvalumab and Tremelimumab

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A to 18 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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)

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Research SiteBaltimoreMarylandUnited States21231
    2Research SiteBostonMassachusettsUnited States02115
    3Research SiteNew Hyde ParkNew YorkUnited States11040
    4Research SiteOklahoma CityOklahomaUnited States73104
    5Research SiteCharlestonSouth CarolinaUnited States29425
    6Research SiteSalt Lake CityUtahUnited States84132
    7Research SiteWashingtonVirginiaUnited States20010
    8Research SiteLille CedexFrance59020
    9Research SiteMarseilleFrance13385
    10Research SiteParis Cedex 05France75248
    11Research SiteVandoeuvre les Nancy CedexFrance54511
    12Research SiteJenaGermany07747
    13Research SiteKoelnGermany50937
    14Research SiteGenovaItaly16100
    15Research SiteMilanoItaly20133
    16Research SiteRomeItaly00165
    17Research SiteTorinoItaly10126
    18Research SiteUtrechtNetherlands3584 CS
    19Research SiteBarcelonaSpain08035
    20Research SiteMadridSpain28009
    21Research SiteLeedsUnited KingdomLS1 3EX
    22Research SiteLondonUnited KingdomWC1N 3JH
    23Research SiteSuttonUnited KingdomSM2 5PT

    Sponsors and Collaborators

    • AstraZeneca

    Investigators

    • Study Director: Ashok Gupta, MD, PhD, AstraZeneca Global Medicines Development, Academy House

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT03837899
    Other Study ID Numbers:
    • D419EC00001
    First Posted:
    Feb 12, 2019
    Last Update Posted:
    Mar 28, 2022
    Last Verified:
    Mar 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    Yes
    Keywords provided by AstraZeneca
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Mar 28, 2022