Clinical Trial of SBRT and Systemic Pembrolizumab With or Without Avelumab/Ipilimumab+ Dendritic Cells in Solid Tumors

Sponsor
Universitair Ziekenhuis Brussel
Study ID
NCT04571632
Phase
PHASE2
Status
Unknown

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Avelumab — DRUG
    Avelumab (200mg/10mL solution) will be administered by intratumoral injection at a maximum total dose of 40 mg (= 2 ml of a 200mg/10ml solution) on day 1 followed by a subsequent intratumoral injections on day 15, 29, 43, 57 and 71. Total administered dose of avelumab (200mg/10mL solution) will be up to 2.0 mL per treatment. Injected volume per lesion will range from 0.05 mL for lesions \< 0,5 cm to 2.0 mL for lesions \> 5 cm in longest diameter. Injection of all lesions in individual patients will not be required.
  • Ipilimumab 5 MG/ML — DRUG
    Ipilimumab (50mg/10mL solution) will be administered by intratumoral injection at a maximum total dose of 10 mg (= 2 ml of a 50mg/10ml solution) on day 1 followed by a subsequent intratumoral injections on day 15, 29, 43, 57 and 71. Total administered dose of ipilimumab (50mg/10mL solution) will be up to 2.0 mL per treatment. Injected volume per lesion will range from 0.05 mL for lesions \< 0,5 cm to 2.0 mL for lesions \> 5 cm in longest diameter. Injection of all lesions in individual patients will not be required. Determination of ipilimumab (50mg/10mL solution) injection volume based on lesion size
  • Pembrolizumab 100 MG in 4 ML Injection — DRUG
    The first administration of pembrolizumab 200 mg (100 mg/4mL solution) by the intravenous route during 30 minutes will be administered on day 1. The second administrations of pembrolizumab 200 mg will be administered by a 30 minutes intravenous infusion on day 21, and thereafter every 21 days (or up to ± 3 days before or after the scheduled date if necessary) days.
  • CD1c (BDCA-1)+ / CD141 (BDCA-3)+ myDC — OTHER
    CD1c (BDCA-1)+ / CD141 (BDCA-3)+ myDC will be administered by intratumoral injection in the lesions that were injected by avelumab en ipilimumab on day 1 (approximately 24 hours after intratumoral injection of avelumab en ipilimumab). The total administered CD1c (BDCA-1)+/ CD141 (BDCA-3)+ myDC volume will be up to 4.0 mL per intratumoral treatment session. Injected volume per lesion (skin-, soft tissue or lymph-node metastases) will range from 0.1 mL for lesions \< 0,5 cm to 4.0 mL for lesions \> 5 cm in longest diameter. Injection of all lesions in an individual patient will not be required. The determination of CD1c (BDCA-1)+ / CD141 (BDCA-3)+ myDC injection volume is based on lesion size. When lesions are clustered together, they are injected as a single lesion according to the table for determination of CD1c (BDCA-1)+ / CD141 (BDCA-3)+ myDC injection volume based on lesion size.

Study Details

A randomized phase II clinical trial of SBRT and systemic pembrolizumab with or without intratumoral avelumab/ipilimumab plus CD1c (BDCA-1)+/CD141 (BDCA-3)+ myeloid dendritic cells in solid tumors.

Key Dates

Start date
Sep 22, 2020
Status verified
Feb 2022
Primary completion
Dec 31, 2023
Completion
Dec 31, 2023

Study Design

Enrollment
36 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Active Comparator: Immediate treatment arm:
    On day -3, -1 and 1, SBRT fractions of 8 Gy will be administered to subjects. On day 1, approximately 2 hours after the last SBRT fraction, intratumoral injection of ipilimumab (Yervoy®, 50mg/10mL solution) at a maximum total dose of 10 mg (= 2 ml of a 50mg/10ml solution) and avelumab (Bavencio®, 200mg/10mL solution) at maximum total dose of 40 mg (= 2 ml of a 200mg/10ml solution) will be performed. Subject will also receive a standard 200mg (fixed dose) intravenous infusion of pembrolizumab (Keytruda®, 100 mg/4mL solution). On day 2, autologous, non-substantially manipulated CD1c (BDCA-1)+ / CD141 (BDCA-3)+ myDC will be intratumorally administered. Previously cryopreserved CD1c (BDCA-1)+ / CD141 (BDCA-3)+ myDC will be thawed before administration. On day 21 and every 21 days thereafter, IT injection of ipilimumab and avelumab and IV pembrolizumab at the same dose as on day 1 will be performed. Treatment will be discontinued upon disease progression
  • Active Comparator: Contemporary control arm
    On day -3, -1 and 1, SBRT fractions of 8 Gy will be administered to subjects. On day 1 and every + 21 days thereafter, subjects will receive a standard 200mg (fixed dose) IV pembrolizumab (Keytruda®, 100 mg/4mL solution) dose. On disease progression, intratumoral administration as in the "immediate-treatment" arm will be conducted. Thus, intratumoral injection of ipilimumab at a maximum total dose of 10 mg and avelumab at maximum total dose of 40 mg will be performed. Administration of pembrolizumab at a dose of 200 mg will be continued. Tumor response assessments by whole body PET/CT will be scheduled in week 12 and every 12 weeks thereafter during the treatment phase; . Baseline scan will be performed during screening period Procurement of tumor tissue by fine needle aspirates will be performed at the time of every intra-tumoral study drug administration

Primary Outcome Measure

1 year progression free survival [ Time Frame: 1 year ]

Central Contacts

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