A clinical study to evaluate the safety, tolerability and early efficacy of the study drug (Durvalumab) alone and a combination of study drugs (Durvalumab and Tremelimumab) in children with advance solid tumours and blood cancer

Phase 1

• Conditions: Advanced Solid Tumors and Hematological Malignancies; MedDRA version: 20.1 Level: LLT Classification code 10065143 Term: Malignant solid tumour System Organ Class: 100000004864; MedDRA version: 20.1 Level: LLT Classification code 10066481 Term: Hematological malignancy System Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-003118-42-ES
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-04-12
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 228

Inclusion Criteria

• Patients must have pathologically confirmed relapsed or refractory advanced solid tumour malignancy or haematological malignancies including lymphoma and acute leukaemia. Any number of prior treatment regimens allowed. A select group of first-line patients may be eligible for screening and enrolment. These patients will be enrolled based on investigator assessment as patients for whom no curative standard of care treatment options exist or such therapies are not tolerable.

• If available, patients must provide a diagnostic tumor sample taken ?3 years prior to screening for evaluation of PD-L1 status.

• Lansky play performance scale =50 for patients =1 and <16 years of age and Karnofsky performance status score =50 for patients =16 years of age (patients <1 year of age are exempt from this criterion)

• Patients must have measurable/evaluable disease as defined by methods used in common clinical practice.

• No prior exposure to immune-mediated therapy including, but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD-L1, anti-PD-L2 antibodies and antibodies of CAR-T or other cell therapies, excluding therapeutic anticancer vaccines. Exposure to other investigational agents may be permitted after discussion with the Sponsor or designee.
Are the trial subjects under 18? yes
Number of subjects for this age range: 228
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

• History of allogeneic organ transplantation (exceptions may be allowed for HL, NHL, ALL and AML, after discussion with Sponsor or designee). Patients who have previously received an autologous bone marrow transplant may be eligible

• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease, diverticulitis, celiac disease or other serious GI chronic conditions associated with diarrhea, systemic lupus erythematosus, Wegener syndrome; myasthenia gravis, Graves’ disease, rheumatoid arthritis, hypophysitis, uveitis, etc). The following are exceptions to this criterion:
- Patients with vitiligo or alopecia
- Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement
- Psoriasis that does not require systemic therapy
- Patients with celiac disease controlled by diet alone.

• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, cardiac arrhythmia, ILD, or psychiatric illness or social situations that would limit compliance with study requirements, substantially increase risk of incurring AEs from IP, or compromise the ability of the patient to give written informed consent.

• History of primary immunodeficiency.

• Active infection including tuberculosis, hepatitis B, hepatitis C, or HIV. Patients with a past or resolved HBV infection are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA).

• Any unresolved toxicity NCI CTCAE version 5.0 Grade =2 from previous anticancer therapy with the exception of alopecia, vitiligo, lymphopenia and the laboratory values defined in the inclusion criteria
- Patients with Grade =2 neuropathy will be evaluated on a case-by-case basis and may be included after consultation with the Study Physician.
- Patients with toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab (eg, hearing loss, gastrostomy tube) may be included after consultation with the Study Physician.

• Patients with clinically active brain metastases (known or suspected) or spinal cord compression are excluded, unless these conditions have been previously treated and are considered stable.

• History of leptomeningeal carcinomatosis, or involvement of any other anatomic area that, in the opinion of the Investigator, may cause significant symptoms if an inflammatory reaction occurs.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified