AMENDMENT TITLE: Phase I clinical trial on intratumoral administration of own non manipulated cells plus ipilimumab and AS01 in combination with intravenously administered nivolumabAMENDMENT 5 TITLE: A randomized phase II clinical trial on intratumoral AS01B/ipilimumab plus intravenous nivolumab with or without autologous CD1c(BDCA-1)+ / CD141(BDCA-3)+ myeloid dendritic cells.

Phase 1

• Conditions: Patients with injectable metastases from histologically confirmed solid tumors who have failed standard-of-care life prolonging therapeutic options will be invited to participate in this clinical trial.; MedDRA version: 20.0Level: LLTClassification code 10007050Term: CancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-003280-35-BE
• Lead Sponsor: Z Brussel

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-08-23
• Last Update Posted: 19 December 2023

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 18

Inclusion Criteria

1)Subject has provided informed consent prior to initiation of any study-specific activities/procedures.
2)Male or female age = 18 years at the time of informed consent
3)All subjects must have histologically confirmed advanced cancer that cannot be completely surgically resected and have failed all standard curative and life prolonging therapy.
4)All subjects must have non-visceral metastatic disease localizations that are amenable to intra-tumor injection by clinical and ultrasound (US) guidance. These metastases should be amenable to a safe post-injection biopsy (partial or complete).
5)ECOG performance status of 0 or 1
6)Candidate for intralesional therapy defined as either one of the following:
a)At least 1 injectable cutaneous, subcutaneous, or solid tumor lesion = 10 mm in longest diameter
b)Multiple injectable solid tumor lesions that in aggregate have a longest diameter of = 10 mm injectable disease
7)Adequate organ function determined within 28 days prior to enrollment, defined as follows:
a)Hematological
i)Absolute neutrophil count = 1500/mm3 (1.5x109/L)
ii)Platelet count: = 75.000/mm3 (7.5x109/L)
iii)Hemoglobin: = 8 g/dL (without need for hematopoietic growth factor or transfusion support)
b)Renal
i)Serum creatinine: 1.5 x upper limit of normal (ULN), OR 24-hour creatinine clearance = 60 mL/min for subject with creatinine levels > 1.5 x ULN. (Note: Creatinine clearance need not be determined if the baseline serum creatinine is within normal limits. Creatinine clearance should be calculated per institutional standard).
c)Hepatic
i)Serum bilirubin: 1.5 x ULN OR direct bilirubin = ULN for a subject with total bilirubin level > 1.5 x ULN
ii)Aspartate aminotransferase (AST): 2.5 x ULN OR = 5 x ULN for subject with liver metastases
iii)Alanine aminotransferase (ALT): 2.5 x ULN OR = 5 x ULN for subject with liver metastases
d)Coagulation
i)International normalization ratio (INR) or prothrombin time (PT): 1.5 x ULN unless the subject is receiving anticoagulant therapy as long as PT and partial thromboplastin time (PTT)/ activated PTT (aPTT) is within therapeutic range of intended use of anticoagulants
ii)PTT or aPTT: 1.5 x ULN unless the subject is receiving anticoagulant therapyas long as PT and PTT/aPTT is within therapeutic range of intended use of anticoagulants
8)Female subject of childbearing potential should have a negative serum pregnancy test within 72 hours prior to enrollment.
9)Subject has a tumor sample (archival sample obtained within 3 months prior to study participation or newly obtained biopsy). Subject must submit the tumor sample during screening. Subjects with a non-evaluable archival sample may obtain a new biopsy and subjects with a non-evaluable newly obtained biopsy may undergo re-biopsy at the discretion of the investigator.
10)Adequate vascular access to undergo a leukapheresis.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 18
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 18

Exclusion Criteria

1)Known active central nervous system (CNS) metastases. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids >10 mg/day of prednisone or equivalent. The exception does not include leptomeningeal metastasis which is excluded regardless of clinical stability.
2)History or evidence of active autoimmune disease that requires systemic treatment (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
3)History or evidence of cancer associated with immunodeficiency states (e.g., hereditary immune deficiency, organ transplant, or leukemia)
4)History of other malignancy within the past 5 years with exceptions
2)Prior treatment of another tumor vaccine
3)Receive live vaccine within 28 days prior to enrollment
4)Prior chemotherapy, radiotherapy, biological cancer therapy, targeted therapy, or major surgery within 28 days prior to enrollment or has not recovered to CTCAE grade 1 or better from adverse event due to cancer therapy administered more than 28 days prior to enrollment.
5)Currently receiving treatment in another investigational device or drug study, or less than 28 days since ending treatment on another investigational device or drug study
6)Expected to require other cancer therapy while on study with the exception of local radiation treatment to the site of bone and other metastasis for palliative pain management
7)Other investigational procedures while participating in this study are excluded.
8)History or evidence of symptomatic autoimmune pneumonitis, glomerulonephritis, vasculitis, or other symptomatic autoimmune disease, or active autoimmune disease or syndrome that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs) except vitiligo or resolved childhood asthma/atopy. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
9)Evidence of clinically significant immunosuppression
10)Known human immunodeficiency virus (HIV) disease
11)Known acute or chronic hepatitis B or hepatitis C infection
12)Known syphilis infection
13)Female subject is pregnant or breast-feeding, or planning to become pregnant during study treatment and through 5 months after the last dose of study treatment
14)Female subject of childbearing potential who is unwilling to use acceptable method(s) of effective contraception during study treatment and through 5 months after the last dose of study treatment.
15)Male subject who is unwilling to use acceptable method of effective contraception during trial participation and through 5 months after the last dose of study treatment. For this trial, male subjects will be considered to be of non-reproductive potential if they have azoöspermia (whether due to having had a vasectomy or due to an underlying medical condition). Note: Acceptable methods of effective contraception are defined in the inform

Study & Design

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