Back to resultsDurvalumab and Tremelimumab for Pediatric Malignancies
Primary Purpose
Pediatric Cancer, Solid Tumor Pediatric, Hematological Malignancies
Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Durvalumab / Tremelimumab Combination Therapy
Sponsored by
About this trial
This is an interventional treatment trial for Pediatric Cancer focused on measuring Pediatric, solid tumors, hematological malignancies, durvalumab, tremelimumab, immunotherapy
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)
Sites / Locations
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Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Durvalumab / Tremelimumab Combination Therapy
Arm Description
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)
Outcomes
Primary Outcome Measures
Dose Finding phase: Recommended Phase 2 Dose
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
Safety and Tolerability
Evaluated based on adverse events occurring throughout the study
Objective Response Rate (dose expansion phase only)
Number (%) of patients achieving complete or partial response according to RECIST 1.1. (solid tumors) and disease-specific response criteria.
Secondary Outcome Measures
Pharmacokinetics (PK) of Durvalumab and Tremelimumab
Serum concentrations of Durvalumab and Tremelimumab
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03837899
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.
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 7, 2019 (Actual)
Primary Completion Date
February 28, 2023 (Actual)
Study Completion Date
December 29, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
4. Oversight
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
Data Monitoring Committee
Yes
5. 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.
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pediatric Cancer, Solid Tumor Pediatric, Hematological Malignancies
Keywords
Pediatric, solid tumors, hematological malignancies, durvalumab, tremelimumab, immunotherapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Durvalumab / Tremelimumab Combination Therapy
Arm Type
Experimental
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
Durvalumab / Tremelimumab Combination Therapy
Other Intervention Name(s)
durvalumab: Imfinzi, MEDI4736, tremelimumab: CP-675,206
Intervention Description
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.
Primary Outcome Measure Information:
Title
Dose Finding phase: Recommended Phase 2 Dose
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
Time Frame
15 months
Title
Safety and Tolerability
Description
Evaluated based on adverse events occurring throughout the study
Time Frame
Up to 4 years.
Title
Objective Response Rate (dose expansion phase only)
Description
Number (%) of patients achieving complete or partial response according to RECIST 1.1. (solid tumors) and disease-specific response criteria.
Time Frame
up to 4 years.
Secondary Outcome Measure Information:
Title
Pharmacokinetics (PK) of Durvalumab and Tremelimumab
Description
Serum concentrations of Durvalumab and Tremelimumab
Time Frame
15 months.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
0 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ashok Gupta, MD, PhD
Organizational Affiliation
AstraZeneca Global Medicines Development, Academy House
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States
Facility Name
Research Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Research Site
City
New Hyde Park
State/Province
New York
ZIP/Postal Code
11040
Country
United States
Facility Name
Research Site
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Research Site
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Research Site
City
Lille Cedex
ZIP/Postal Code
59020
Country
France
Facility Name
Research Site
City
Marseille
ZIP/Postal Code
13385
Country
France
Facility Name
Research Site
City
Paris Cedex 05
ZIP/Postal Code
75248
Country
France
Facility Name
Research Site
City
Köln
ZIP/Postal Code
50924
Country
Germany
Facility Name
Research Site
City
Genova
ZIP/Postal Code
16100
Country
Italy
Facility Name
Research Site
City
Milano
ZIP/Postal Code
20133
Country
Italy
Facility Name
Research Site
City
Rome
ZIP/Postal Code
00165
Country
Italy
Facility Name
Research Site
City
Torino
ZIP/Postal Code
10126
Country
Italy
Facility Name
Research Site
City
Utrecht
ZIP/Postal Code
3584 CS
Country
Netherlands
Facility Name
Research Site
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Research Site
City
Madrid
ZIP/Postal Code
28009
Country
Spain
Facility Name
Research Site
City
Leeds
ZIP/Postal Code
LS1 3EX
Country
United Kingdom
Facility Name
Research Site
City
London
ZIP/Postal Code
WC1N 3JH
Country
United Kingdom
Facility Name
Research Site
City
Sutton
ZIP/Postal Code
SM2 5PT
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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
IPD Sharing 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
IPD Sharing 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
IPD Sharing URL
https://astrazenecagroup-dt.pharmacm.com/DT/Home
Learn more about this trial
Durvalumab and Tremelimumab for Pediatric Malignancies
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