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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 : April 17, 2019
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE January 24, 2019
First Posted Date  ICMJE February 12, 2019
Last Update Posted Date April 17, 2019
Actual Study Start Date  ICMJE March 7, 2019
Estimated Primary Completion Date October 18, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 8, 2019)
  • 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
  • Safety and Tolerability [ Time Frame: Up to 4 years. ]
    Evaluated based on adverse events occurring throughout the study
  • 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03837899 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 8, 2019)
Pharmacokinetics (PK) of Durvalumab and Tremelimumab [ Time Frame: 15 months. ]
Serum concentrations of Durvalumab and Tremelimumab
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Durvalumab and Tremelimumab for Pediatric Malignancies
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Pediatric Cancer
  • Solid Tumor Pediatric
  • Hematological Malignancies
Intervention  ICMJE 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
Study Arms  ICMJE 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.

Intervention: Drug: Durvalumab / Tremelimumab Combination Therapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 18, 2019)
158
Original Estimated Enrollment  ICMJE
 (submitted: February 8, 2019)
156
Estimated Study Completion Date  ICMJE March 20, 2023
Estimated Primary Completion Date October 18, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Contact: AstraZeneca Cancer Study Locator 877-400-4656
Listed Location Countries  ICMJE France,   Germany,   Italy,   Netherlands,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03837899
Other Study ID Numbers  ICMJE D419EC00001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Dana Ghiorghiu, MD, PhD AstraZeneca Global Medicines Development, Academy House
PRS Account AstraZeneca
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP