NCT07288112Phase 1, Phase 2Recruiting
Diakonos Oncology Corporation · The University of Alabama at Birmingham, Birmingham, Alabama
The goal of this clinical trial is to learn if DOC1021 + pIFN will be safe and will lead to tumor responses in patients with refractory melanoma. DOC1021 is a dendritic cell immunotherapy derived from a patient's own blood cells and loaded with antigens from the patient's tumor in the form of tumor lysate and mRNA. The goal is to stimulate a T cell immune response that eliminates tumor cells.
The study consists of two components: an initial phase I safety study to confirm safety/tolerability of the treatment regimen, and, subsequently, a single-arm phase II cohort to assess efficacy of the treatment regimen.
All participants will:
* Undergo a leukapheresis collection (take filgrastim subcutaneously x 5 doses, if clinically necessary, leading up to collection)
* Receive two doses of DOC1021 under image guidance 2 weeks apart
* Receive subcutaneous pIFN injections weekly for a total of 4 doses in parallel with the DOC1021 injections
* Undergo an optional image-guided perinodal DOC1021 booster injection approximately 6 months after the first DOC1021 dose along with additional subcutaneous pIFN injections at time of the booster and the subsequent week for a total of 2 pIFN doses
* Visit the clinic regularly to assess quality of life, symptoms, medication use, imaging, bloodwork, and to receive optional treatment with anti-PD1 agents
Eligibility: 18 Years to · All · 1. Provision of signed and dated informed consent form
2. Stated willingness to comply with all study procedures and avail-ability for the duration of the study
3. Age 18 years or older
4. Patients diagnosed with unresectable or metastatic melanoma and progressed following ≥1 prior systemic therapy including anti-PD-1 (i.e., refractory to anti-PD-1). Refractory defined as primary or secondary resistance as per SITC guidelines, except that confirmatory scan not required if clinical progression requiring surgery or radiation to relieve symptoms
5. Willing and able to withhold anti-PD-1 treatment from the time of enrollment through at least 6 weeks after the first DOC1021 administration
6. One or more lesions available for biopsy or resection expected to yield at least 50 mg and preferably 100 mg of tumor for generating DOC1021 and at least 1 measurable target tumor lesion evaluable after DOC1021 by RECIST version 1.1.
7. Brain metastases allowed if stable after prior treatment
8. Ability to receive leukapheresis (with filgrastim if clinically indicated) and perinodal injections of DOC1021 near regional nodes + weekly pIFN x 4 weeks (i.e., sufficient clinical stability and anticipated life expectancy to complete the treatment period and allow time for an immune response to develop).
9. Females of reproductive potential must have a negative serum pregnancy test and agree to use effective contraception (as deter-mined appropriate for the patient by the investigator) during study treatment.
10. Adequate kidney, liver, bone marrow function, and immune function, as follows:
1. Hemoglobin ≥ 8.0 gm/dL (use of transfusion or other intervention to achieve is acceptable)
2. Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3
3. Platelet count ≥ 75,000/mm3
4. Calculated creatinine clearance (CrCl) \> 30 mL/min using Cockcroft and Gault formula:
i. For males = (140 - age\[years\]) x (body weight \[kg\]) / (72 x serum creatinine \[mg/dL\]) ii. For females = 0.85 x value from male formula e. Total bilirubin ≤ 1.5 times upper limit of normal (ULN) except in patients with Gilbert's disease for which total bilirubin must be ≤ 3 times ULN f. Aspartate transaminase AST (SGOT) and alanine aminotransferase ALT (SGPT) ≤ 3 times the ULN (or ≤ 5.0 × ULN if liver metastases)
11. Eastern Cooperative Oncology Group (ECOG) Performance Score 0 or 1
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.
NCT07198165Phase 2Recruiting
Ruijin Hospital · Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai
This study aims to evaluate the efficacy and safety of short-course radiotherapy combined with CAPOX plus bevacizumab with or without a PD-1 inhibitor in patients with locally advanced rectal cancer (LARC). The hypothesis is that the addition of immunotherapy (PD-1 inhibitor) can significantly improve the complete response (CR) rate and enhance local control while reducing the incidence of distant metastasis. This study will compare the effects of sequential chemoradiotherapy and targeted therapy with or without immunotherapy following short-course radiotherapy, aiming to explore the optimal regimen for total neoadjuvant therapy.
Eligibility: 18 Years to 75 Years · All · * Histopathologically confirmed rectal adenocarcinoma with no prior antitumor therapy.
* Exclusion of patients with BRAF mutations or MSI-H status, as determined by pre-enrollment genetic testing including RAS, BRAF, and MSI analysis. RAS mutation status is permitted regardless.
* Absence of severe intestinal obstruction symptoms and no evidence of distant metastasis confirmed by imaging examinations such as CT, MRI, or PET/CT.
* Confirmation as locally advanced rectal cancer by rectal MRI, meeting one or more of the following criteria: T3c-d or T4, N2, EMVI(+), MRF(+), lateral lymph node metastasis; or patients with low-lying rectal cancer (≤5 cm from the anal verge) unsuitable for sphincter-preserving surgery prior to neoadjuvant therapy.
* Age 18 to 75 years.
* ECOG Performance Status of 0 to 1, without severe comorbid medical conditions.
* Adequate organ function:
Hematopoietic: Hemoglobin ≥90 g/L, Platelets ≥80 × 10\^9/L, Absolute Neutrophil Count ≥1.5 × 10\^9/L.
Hepatic: ALT and AST \< 2.5 × ULN. Renal: Serum Creatinine \< 1.5 × ULN.
* Provision of signed and dated written informed consent.
NCT07646639Phase 2Recruiting
The First Affiliated Hospital with Nanjing Medical University · Jiangsu Province Hospital, Nanjing, Jiangsu
This prospective, randomized phase II trial is designed to evaluate whether low-dose short-course radiotherapy differs from common-dose short-course radiotherapy in terms of efficacy when both regimens are sequentially combined with CAPOX, a PD-1 monoclonal antibody, and interleukin-2 (IL-2) in patients with locally advanced rectal cancer. The study is based on findings from our previous single-center, single-arm PRIDE01 study, in which neoadjuvant short-course radiotherapy followed by systemic chemoimmunotherapy and IL-2 demonstrated encouraging antitumor activity relative to historical short-course radiotherapy-based approaches. The current trial aims to provide more robust clinical evidence regarding the potential role of low-dose radiotherapy combined with IL-2 as a sensitization strategy in multimodal neoadjuvant therapy. By comparing complete response rates between the two radiotherapy dose levels, this study may help define an optimized neoadjuvant approach and support future organ-preservation strategies for patients with locally advanced rectal cancer.
Eligibility: 18 Years to 70 Years · All · 1. Male and female patients aged 18 to 70 years.
2. Histologically confirmed rectal adenocarcinoma with the distal margin of the tumor located within 12 cm of the anal verge.
3. MRI-based clinical stage T3-T4 or any T with lymph node-positive (N+) disease.
4. Adequate hematologic, hepatic, and renal function defined as: absolute neutrophil count \>=1.5 x 10\^9/L; platelet count \>=75 x 10\^9/L; serum total bilirubin \<=1.5 x upper normal limit (UNL); aspartate aminotransferase \<=2.5 x UNL; alanine aminotransferase \<=2.5 x UNL; serum creatinine \<=1.5 x UNL.
5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
NCT07676461Phase IIRecruiting
Centro de Tratamiento e Investigación sobre Cáncer, Luis Carlos Sarmiento Angulo · Fundación CTIC - Centro de Tratamiento e Investigación sobre Cáncer Luis Carlos Sarmiento Angulo, Bogotá, Bogota D.C.
This is a prospective observational cohort study conducted at Fundación CTIC in Bogotá, Colombia. It characterizes the oral, fecal and intratumoral microbiome of Colombian adults with advanced solid tumors (gastric, colorectal, breast, cervical and head-and-neck cancer) who receive first-line immunotherapy as standard of care, and compares them with healthy volunteers. Using multi-omics (HiFi metagenomics, 16S, tumor RNA-Seq and untargeted metabolomics), the study aims to identify microbial signatures associated with treatment response and survival, building the initial Colombian cohort of a Cancer Microbiome Atlas with Latin American projection.
Eligibility: 18 Years to · All · * Age 18 years or older.
* Histologically confirmed advanced (stage III unresectable or IV) gastric, colorectal, breast, cervical or head-and-neck cancer.
* Candidate for first-line immunotherapy per current clinical guidelines.
* Available FFPE tumor block in institutional or reference pathology archive.
* Able to provide saliva and stool samples at V0 and follow-up.
* ECOG performance status within protocol limits; life expectancy over 3 months.
* Cognitive capacity to give informed consent; signed EVA-BIOBANCO and Atlas consents.
Inclusion Criteria (healthy controls)
* No prior cancer diagnosis.
* No active autoimmune disease; no inflammatory bowel disease.
* No antibiotics, invasive dental treatment, immunosuppressants or corticosteroids in the prior 3 months; no severe active periodontal disease.
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.
NCT07759856Phase 2Recruiting
Tianjin First Central Hospital · Tianjin First Central Hospital, Tianjin, Tianjin Municipality
This research study is designed for patients with extensive-stage small cell lung cancer (ES-SCLC) who have already received four cycles of standard chemotherapy, with at least two cycles combined with immunotherapy, and have achieved disease control (stable disease, partial response, or complete response) at their last efficacy evaluation.
In this study, participants will be randomly assigned to one of two groups:
Group A will receive standard immunotherapy plus 1 to 3 courses of allogeneic natural killer (NK) cell therapy. Each course consists of six NK cell infusions given over 28 days.
Group B will receive standard immunotherapy alone. All participants will continue treatment until their disease progresses or they experience unacceptable side effects. The immunotherapy agents used in this study are those recommended by major international and national clinical guidelines for extensive-stage SCLC, including but not limited to durvalumab, atezolizumab, serplulimab, and adebrelimab.
The purpose of this study is to evaluate whether adding NK cell therapy to standard immunotherapy can provide additional benefits for patients with extensive-stage SCLC who have responded well to initial treatment.
Eligibility: 18 Years to · All · * 1: Male or female, aged 18 years or above
2: ECOG score 0-2
3: metastatic or extensive-stage small cell lung cancer (SCLC) confirmed by histology or cytology, followed by 4 cycles of platinum-based doublet-chemotherapy with at least 2 cycles of immune checkpoint inhibitor plus chemotherapy. And stable disease (SD), partial response (PR), or complete response (CR) as assessed by imaging (RECIST1.1 criteria) after the last treatment. (The checkpoint inhibitors used were those recommended by the NCCN, ESMO, and CSCO guidelines for extensivestage SCLC, including but not limited to: Duvalumab, atezolizumab, slulizumab, adbelimumab, toripalimab, etc.)
4: After standard concurrent chemoradiotherapy, LS-SCLC could be enrolled in this study if sensitive relapse (relapse more than 6 months after the end of first-line treatment) progressed to extensive-stage (Ed) and met the inclusion criteria No.3;
5: At least 4 weeks after major surgery or trauma, and the wound must be completely healed; At least 1 week after minor surgical procedures or trauma (e.g., tissue biopsy or fine-needle aspiration);
6: Objective measurable lesions according to RECIST 1.1 criteria;
7: predicted survival time ≥1 year;
8: bone marrow function: ANC≥1.5×109/L, HB≥70 g/L (blood transfusion allowed), PLT≥80×109/L;
9: Liver function: ALT≤3×ULN, AST≤3×ULN, TBIL≤2×ULN (patients with liver metastasis ALT≤5×ULN, AST≤5×ULN, TBIL≤2×ULN) Child-Pugh score ≤7; Renal function: uric acid \<500 μmol/L, serum creatinine \<1.7 mg/dL, proteinuria ≤2+ or ≤2g/24h, glomerular filtration rate (GFR) ≥60 ml/min/1.73m2;
10: no history of autoimmune diseases or current autoimmune diseases;
11: The subjects voluntarily participated in the study, signed the informed consent form, communicated well with the investigators, and completed the study in accordance with the protocol.
NCT07676461Phase IIRecruiting
Centro de Tratamiento e Investigación sobre Cáncer, Luis Carlos Sarmiento Angulo · Fundación CTIC - Centro de Tratamiento e Investigación sobre Cáncer Luis Carlos Sarmiento Angulo, Bogotá, Bogota D.C.
This is a prospective observational cohort study conducted at Fundación CTIC in Bogotá, Colombia. It characterizes the oral, fecal and intratumoral microbiome of Colombian adults with advanced solid tumors (gastric, colorectal, breast, cervical and head-and-neck cancer) who receive first-line immunotherapy as standard of care, and compares them with healthy volunteers. Using multi-omics (HiFi metagenomics, 16S, tumor RNA-Seq and untargeted metabolomics), the study aims to identify microbial signatures associated with treatment response and survival, building the initial Colombian cohort of a Cancer Microbiome Atlas with Latin American projection.
Eligibility: 18 Years to · All · * Age 18 years or older.
* Histologically confirmed advanced (stage III unresectable or IV) gastric, colorectal, breast, cervical or head-and-neck cancer.
* Candidate for first-line immunotherapy per current clinical guidelines.
* Available FFPE tumor block in institutional or reference pathology archive.
* Able to provide saliva and stool samples at V0 and follow-up.
* ECOG performance status within protocol limits; life expectancy over 3 months.
* Cognitive capacity to give informed consent; signed EVA-BIOBANCO and Atlas consents.
Inclusion Criteria (healthy controls)
* No prior cancer diagnosis.
* No active autoimmune disease; no inflammatory bowel disease.
* No antibiotics, invasive dental treatment, immunosuppressants or corticosteroids in the prior 3 months; no severe active periodontal disease.
