Durvalumab and Tremelimumab for Pediatric Malignancies

• Sponsor: AstraZeneca (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT03837899
• Collaborator: (none)
• Enrollment: 158
• Locations: 22
• Arm: 1
• Anticipated Duration (Months): 57.5
• Patients Per Site: 7.2
• Patients Per Site Per Month: 0.1

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 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 Design

• Study Type: Interventional
• Anticipated Enrollment: 158 participants
• Allocation: Non-Randomized
• 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

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

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: 0 Years 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

	Site	City	State	Country	Postal Code
1	Research Site	Baltimore	Maryland	United States	21231
2	Research Site	Boston	Massachusetts	United States	02115
3	Research Site	New Hyde Park	New York	United States	11040
4	Research Site	Oklahoma City	Oklahoma	United States	73104
5	Research Site	Charleston	South Carolina	United States	29425
6	Research Site	Washington	Virginia	United States	20010
7	Research Site	Lille Cedex		France	59020
8	Research Site	Marseille		France	13385
9	Research Site	Paris Cedex 05		France	75248
10	Research Site	Vandoeuvre les Nancy Cedex		France	54511
11	Research Site	Jena		Germany	07747
12	Research Site	Köln		Germany	50924
13	Research Site	Genova		Italy	16100
14	Research Site	Milano		Italy	20133
15	Research Site	Rome		Italy	00165
16	Research Site	Torino		Italy	10126
17	Research Site	Utrecht		Netherlands	3584 CS
18	Research Site	Barcelona		Spain	08035
19	Research Site	Madrid		Spain	28009
20	Research Site	Leeds		United Kingdom	LS1 3EX
21	Research Site	London		United Kingdom	WC1N 3JH
22	Research Site	Sutton		United Kingdom	SM2 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: Aug 3, 2022
• Last Verified: Aug 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: Pediatric, solid tumors, hematological malignancies, durvalumab, tremelimumab, immunotherapy
• Additional relevant MeSH terms: Neoplasms; Hematologic Neoplasms; Durvalumab; Tremelimumab; Antibodies, Monoclonal

Study Results

No Results Posted as of Aug 3, 2022