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Durvalumab and Tremelimumab for Pediatric Malignancies

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ClinicalTrials.gov Identifier: NCT03837899
Recruitment Status : Recruiting
First Posted : February 12, 2019
Last Update Posted : September 5, 2021
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

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 disease Intervention/treatment Phase
Pediatric Cancer Solid Tumor Pediatric Hematological Malignancies 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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : March 7, 2019
Estimated Primary Completion Date : June 23, 2023
Estimated Study Completion Date : December 22, 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Durvalumab

Arm Intervention/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




Primary Outcome Measures :
  1. Dose Finding phase: Recommended Phase 2 Dose [ Time Frame: 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 [ Time Frame: Up to 4 years. ]
    Evaluated based on adverse events occurring throughout the study

  3. Objective Response Rate (dose expansion phase only) [ Time Frame: 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 [ Time Frame: 15 months. ]
    Serum concentrations of Durvalumab and Tremelimumab



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03837899


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Contact: AstraZeneca Cancer Study Locator 877-400-4656

Locations
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United States, Maryland
Research Site Recruiting
Baltimore, Maryland, United States, 21231
United States, Massachusetts
Research Site Recruiting
Boston, Massachusetts, United States, 02115
United States, New York
Research Site Recruiting
New Hyde Park, New York, United States, 11040
United States, Oklahoma
Research Site Recruiting
Oklahoma City, Oklahoma, United States, 73104
United States, South Carolina
Research Site Recruiting
Charleston, South Carolina, United States, 29425
United States, Utah
Research Site Withdrawn
Salt Lake City, Utah, United States, 84132
United States, Virginia
Research Site Recruiting
Washington, Virginia, United States, 20010
France
Research Site Recruiting
Lille Cedex, France, 59020
Research Site Recruiting
Marseille, France, 13385
Research Site Recruiting
Paris Cedex 05, France, 75248
Research Site Recruiting
Vandoeuvre les Nancy Cedex, France, 54511
Germany
Research Site Recruiting
Jena, Germany, 07747
Research Site Recruiting
Koeln, Germany, 50937
Italy
Research Site Recruiting
Genova, Italy, 16100
Research Site Recruiting
Milano, Italy, 20133
Research Site Recruiting
Rome, Italy, 00165
Research Site Recruiting
Torino, Italy, 10126
Netherlands
Research Site Recruiting
Utrecht, Netherlands, 3584 CS
Spain
Research Site Recruiting
Barcelona, Spain, 08035
Research Site Recruiting
Madrid, Spain, 28009
United Kingdom
Research Site Recruiting
Leeds, United Kingdom, LS1 3EX
Research Site Recruiting
London, United Kingdom, WC1N 3JH
Research Site Recruiting
Sutton, United Kingdom, SM2 5PT
Sponsors and Collaborators
AstraZeneca
Investigators
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Study Director: Ashok Gupta, MD, PhD AstraZeneca Global Medicines Development, Academy House
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03837899    
Other Study ID Numbers: D419EC00001
First Posted: February 12, 2019    Key Record Dates
Last Update Posted: September 5, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

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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:
Pediatric, solid tumors, hematological malignancies, durvalumab, tremelimumab, immunotherapy
Additional relevant MeSH terms:
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Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Hematologic Diseases
Durvalumab
Tremelimumab
Antibodies, Monoclonal
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs