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Durvalumab and Tremelimumab for Pediatric Malignancies

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ClinicalTrials.gov Identifier: NCT03837899
Recruitment Status : Not yet recruiting
First Posted : February 12, 2019
Last Update Posted : February 19, 2019
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.


Study Type : Interventional
Estimated Enrollment : 158 participants
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
Estimated Study Start Date : February 11, 2019
Estimated Primary Completion Date : September 22, 2021
Estimated Study Completion Date : October 31, 2024

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 2-5. (solid tumors, hematological malignancies and HL)

* Patients in the Hodgkin lymphoma cohort will receive durvalumab as monotherapy, administered every 4 weeks as an intravenous infusion. Tremelimumab may be added for 4 doses at time of progression.

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. HL cohort will only receive durvalumab monotherapy in 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



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Ages Eligible for Study:   up to 17 Years   (Child)
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
  • Malignant neoplasms of hematopoietic and lymphoid tissue and myelodysplastic syndrome: pathologically confirmed relapsed or refractory advanced hematological malignancies including lymphoma and acute leukemia
  • 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 HL, NHL, ALL and AML, 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
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Contact: AstraZeneca Cancer Study Locator 877-400-4656

Locations
United States, Maryland
Research Site Not yet recruiting
Baltimore, Maryland, United States, 21231
United States, Massachusetts
Research Site Not yet recruiting
Boston, Massachusetts, United States, 02115
United States, New York
Research Site Not yet recruiting
New Hyde Park, New York, United States, 11042
United States, Oklahoma
Research Site Not yet recruiting
Oklahoma City, Oklahoma, United States, 73104
United States, South Carolina
Research Site Not yet recruiting
Charleston, South Carolina, United States, 29425
United States, Texas
Research Site Not yet recruiting
Fort Worth, Texas, United States, 76104
France
Research Site Not yet recruiting
Lille Cedex, France, 59020
Research Site Not yet recruiting
Marseille CEDEX 5, France, 13385
Research Site Not yet recruiting
Paris Cedex 05, France, 75248
Research Site Not yet recruiting
Vandoeuvre les Nancy Cedex, France, 54511
Germany
Research Site Not yet recruiting
Jena, Germany, 07747
Research Site Not yet recruiting
Koeln, Germany, 50937
Italy
Research Site Not yet recruiting
Genova, Italy, 16100
Research Site Not yet recruiting
Torino, Italy, 10126
Netherlands
Research Site Not yet recruiting
Utrecht, Netherlands, 3584 CS
United Kingdom
Research Site Not yet recruiting
Leeds, United Kingdom, LS1 3EX
Research Site Not yet recruiting
London, United Kingdom, SW3 6JJ
Research Site Not yet recruiting
London, United Kingdom, WC1N 3JH
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Dana Ghiorghiu, MD, PhD AstraZeneca Global Medicines Development, Academy House

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03837899     History of Changes
Other Study ID Numbers: D419EC00001
First Posted: February 12, 2019    Key Record Dates
Last Update Posted: February 19, 2019
Last Verified: February 2019

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:
Neoplasms
Antibodies, Monoclonal
Tremelimumab
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents