NCT03340129Phase 2Recruiting
Melanoma Institute Australia · Westmead Hospital, Sydney, New South Wales
This is a phase II, open label, randomised trial of ipilimumab and nivolumab with concurrent intracranial stereotactic radiotherapy versus ipilimumab and nivolumab alone in patients with asymptomatic, untreated melanoma brain metastases.
Eligibility: 18 Years to 120 Years · All · Inclusion Criteria:
1. Female or male patients, ≥18 years of age.
2. Signed, written, informed consent.
3. AJCC Stage IV \[any T, any N, M1d (0) or M1D(1)\] histologically confirmed cutaneous, acral or mucosal unresectable melanoma or unknown primary melanoma and at least 1 radiological definitive brain metastasis that is ≥ 5mm and ≤40mm, measurable per RECIST version 1.1 guidelines (modified for brain metastases, enabling up to 5 target lesions in the brain as well as up to 5 extracranial target lesions). There is no upper limit restriction in the number of brain metastases, provided the remaining eligibility criteria are met.
4. The BRAF mutation status must be available prior to randomisation.
5. The treating clinician(s) should consider the intracranial disease amenable to stereotactic radiotherapy over whole brain radiotherapy. Patients for whom there is a definite and immediate indication for radiotherapy (e.g. rapidly progressing disease with associated clinical signs and /or symptoms) should not be considered for enrolment.
6. Brain metastases must be untreated with any modality of radiotherapy or systemic treatment. Previous surgery for melanoma brain metastases is permitted if it resulted in gross total resection and no radiotherapeutic cavity boost was required.
7. No prior systemic treatment for brain metastases is permitted unless given in the neoadjuvant or adjuvant settings for systemic drug the treatment for extracranial disease only. At the time of neoadjuvant or adjuvant systemic therapy for extracranial disease, there should be radiological evidence of the absence of brain metastases. The presenting diagnosis of brain metastases at the time of enrolment in this study must have occurred a minimum of 6 months after stopping neoadjuvant or adjuvant systemic therapy (prior anti PD1, anti PD-L1, anti CTLA-4, BRAF / MEK inhibitors or clinical trial agents) are acceptable in the setting of neoadjuvant or adjuvant treatment
8. Asymptomatic from brain metastases at the time of study enrolment without corticosteroids, analgesia or any other treatment for the management of neurological symptoms (with the exception of antiepileptics prescribed for any reason, provided patient is asymptomatic). Resolved neurological symptoms are permitted if complete resolution, without any intervention, has been sustained for a minimum of 7 days prior to randomisation.
9. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
10. A life expectancy \> 30 days.
11. Able to undergo MRI with Gadolinium contrast agent. CT of the brain is not an acceptable alternative should patients be unable to safely undergo a contrast MRI.
12. Adequate haematological, hepatic and renal organ function as defined by:
1. White cell count ≥ 2.0 × 10x9/L
2. Neutrophil count ≥ 1.5 × 10x9/L
3. Haemoglobin ≥ 90 g/L
4. Platelet count ≥ 100 x 10x9/L
5. Total bilirubin ≤ 1.5 x ULN
6. Alanine transaminase ≤ 3.0 x ULN
7. Aspartate aminotransferase ≤ 3.0 x ULN
8. Serum creatinine ≤ 1.5 x the upper limit of normal (ULN). If serum creatinine is \> 1.5 x ULN, calculate creatinine clearance using standard Cockcroft-Gault formula. Creatinine clearance must be 40ml/min to be eligible.
13. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days of the first dose of study treatment and agree to use effective contraception from 14 days prior to commencing study treatment, throughout the treatment period and for 23 weeks \* after the last dose of study treatment. Effective contraception includes:
1. Intrauterine device with a documented failure rate of less than 1% per year.
2. Vasectomised partner who is sterile prior to the female partner patient's commencement of study treatment and is the sole sexual partner for that female.
3. Combined (oestrogen and progestogen) hormonal contraception associated with inhibition of ovulation or progestogen only hormonal contraception associa
NCT05867004Phase IIRecruiting
Institut Claudius Regaud · Institut Claudius Regaud, Toulouse
Cutaneous melanoma is a bad prognosis skin cancer, which can be treated with immune checkpoint inhibitors (ICI), such as anti-PD-1 (nivolumab, nivo) and anti-CTLA-4 (ipilimumab, ipi). However, about 50% of patients do not respond or relapse within 3 years post therapy induction, and immune-related adverse events (irAEs), such as colitis, are triggered and can be treated with TNF inhibitor (TNFi; ie, infliximab, inflix). The pharmacodynamic impact of TNFi on the immune and clinical responses remain to be clarified. The investigators previously demonstrated that TNFi enhance the efficacy of ICI in mouse melanoma models. Based on preclinical findings, the investigators implemented two clinical trials in advanced melanoma patients, TICIMEL and MELANFalpha. In TICIMEL, patients are concomitantly treated with TNFi \[certolizumab (certo) or inflix\] and ICI (ipi+nivo). In MELANFalpha, patients are treated with ICI alone. Preliminary results show both tritherapies promote systemic MART-1 specific CD8 T cell responses and that certo but not inflix may improve ICI efficacy and Th1 responses. In mouse melanoma models, TNFi enhance the response to ICI. Investigators' primary objective is to decipher how certolizumab and infliximab influence ICI-dependent anti-tumor immune responses in advanced melanoma patients. The secondary objectives are to analyse the cellular and molecular impact anti-TNF have on ICI-dependent anti-melanoma immune responses and clinical activities (irAEs and efficacy). By combining mouse and human data as well ex vivo functional assays, the investigators will dissect the impact treatments have on anti-melanoma immune responses by flow cytometry and transcriptomic analyses. The investigators expect to clarify (i) the mechanisms by which TNFi enhance ICI efficacy, (ii) identify the best TNFi to be combined with ICI in advanced melanoma patients and (iii) discover TNF-dependent biomarkers of resistance.
Eligibility: 18 Years to · All · * Inclusion in TICIMEL clinical trial (NCT03293784),
* Inclusion in MELANFα trial (NCT03348891)
NCT05527795Phase IIRecruiting
Hospices Civils de Lyon · Centre Hospitalier Lyon Sud, Pierre-Bénite
Surgical excision is the treatment of choice for stage II, III and resectable stage IV melanoma and is curative in most cases. Given the recent success of immunotherapy for the treatment of patients with advanced metastatic melanoma, the use of immunotherapy has been evaluated in the adjuvant setting for patients at high risk of recurrence. In this context, Nivolumab prolonged Recurrence-Free Survival (RFS) while reducing toxicity compared with Ipilimumab in a phase III clinical trial, and was subsequently FDA-approved in December 2017 for adjuvant treatment of locally advanced melanoma with metastatic lymph node involvement after resection of cutaneous lesions. While a fraction of patients benefit from adjuvant PD-1 immunotherapy, approximately 40% of patients are still relapsing despite this adjuvant treatment, without being able to identify them early and with poor understanding of resistance mechanisms. Additionally, about 15% of the patients will develop serious adverse effects driven by immunotherapy and often discontinuing or even contraindicating the onset of subsequent treatments, hence affecting global patients care. It is therefore of prime importance to identify clinical features able to predict response and toxicities to adjuvant immunotherapy in melanoma.
Eligibility: 18 Years to · All · * Patients diagnosed with stage II, III or IV (resected) melanoma
* Treated by surgery and adjuvant immunotherapy between January 1st of 2019 and January 1st of 2029
* Gave informed consent to allow the use of biological samples for research purpose
* Has read the information sheet regarding this study
* With tumor samples available at the biobank center
NCT07564570NARecruiting
Universitätsklinikum Hamburg-Eppendorf · University Medical Center Hamburg-Eppendorf, Hamburg, Free and Hanseatic City of Hamburg
The aim of this research project is to determine whether a short bout of physical exercise immediately before the start of immunotherapy (Nivolumab and Ipilimumab) is feasible and has a positive effect on the effectiveness of immunotherapy. It is known that short-term physical exercise leads to marked changes in the innate and adaptive immune system. These changes-specifically an increase in natural killer (NK) cells and cytotoxic T cells-are associated with a better response to immunotherapy.
The patient population selected for this study consists of patients with advanced-stage melanoma who are receiving Nivolumab and Ipilimumab.
First, we aim to assess whether such an intervention is feasible in a large proportion of patients, as many patients experience disease-related and treatment-related side effects.
Secondary objectives are to demonstrate that the exercise intervention positively influences the immune system and that this, in turn, leads to an improved response to therapy, thereby positively affecting patient survival, improving quality of life, and reducing treatment-related side effects.
Eligibility: 18 Years and older · All · * Histologically confirmed metastatic malignant melanoma with an indication for immunotherapy (Nivolumab and Ipilimumab).
* The participant provides written informed consent for the study.
* The participant is at least 18 years of age on the day the informed consent is signed.
* No prior systemic anticancer therapy for metastatic disease (e.g., cytotoxic or targeted agents).
* ECOG (Eastern Cooperative Oncology Group) performance status score of ≤ 2.
* No physical impairment that would preclude participation in physical exercise.
NCT06492421Phase 2Recruiting
Second Affiliated Hospital of Guangzhou Medical University · The Second Affiliated Hospital of Guangzhou Medical University, Guanzhou, Guangdong
This phase II trial studies how well intra-tumor injection of double checkpoint inhibitors work when given alone and in combination with chemotherapy or/and bevacizumab in treating patients with previously untreated stage I-IIIA non-small cell lung cancer. Immunotherapy with monoclonal antibodies, such as ipilimumab, pembrolizumab or durvalumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Drugs used in interventional radiological chemotherapy, such as idabubicin, can directly kill the cancer cell and release tumor antigens to activate DC function in situ. Giving intra-tumor injection of checkpoints inhibitors with or without chemotherapy and/or bevecizumab may work better than in vein infusion of the drugs in treating patients with non-small cell lung cancer.
Eligibility: 18 Years to 75 Years · All · 1. Histologically or cytologically confirmed previously untreated non-small cell lung cancer. If a diagnostic biopsy is available, a pre-treatment biopsy is not required. Patients with a suspected lung cancer are eligible, but pathology must be confirmed prior to initiating treatment on study.
2. Patients with stage IIIA must not have more than one mediastinal lymph node station involved by tumor.
3. All patients must have lymph node evaluation of contralateral stations 2 and/or 4 to exclude N3 disease.
4. The patient must be a suitable candidate for surgery, in the opinion of the treating physician.
5. Signed and dated written informed consent must be provided by the patient prior to admission to the study in accordance with International Conference on Harmonization-Good Clinical Practice (ICH-GCP) guidelines and to the local legislation.
6. Eastern Cooperative Oncology Group (ECOG) performance status score 0-1.
7. Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L; Hemoglobin \>= 8.0 g/dL; Platelets \>= 100 x 10\^9/L; Total bilirubin =\< 1.5 x upper limit of normal (ULN) (except subjects with Gilbert syndrome who can have total bilirubin \< 3.0 mg/dL); Creatinine =\< 1.5 x ULN or calculated creatinine clearance \>= 50 mL/min using Cockcroft-Gault formula for creatinine clearance calculation OR 24-hour urine creatinine clearance \>= 50 mL/min.
