MRD-guided Deferred Adjuvant Therapy in Resectable Early-stage Colon Cancer

Prognostic Impact of Adjuvant Therapy in Primary Hepatic Sarcomatoid Carcinoma

DNA-guided Second Line Adjuvant Therapy for High Residual Risk, Estrogen Receptor Positive, HER-2 Negative Breast Cancer (DARE)

Surveillance population and ctDNA screening (up to 1000 patients): High risk ER positive, HER2-, breast cancer patients who have completed adjuvant endocrine therapy, or are currently receiving adjuvant endocrine therapy with an aromatase inhibitor or tamoxifen and are within 7 years since completion of definitive breast surgery are eligible for ctDNA screening. In order to start ctDNA surveillance, patients must have completed at least 6 months, but no more than 7 years of adjuvant endocrine therapy of treatment without distant recurrence. Prior adjuvant CDK4/6 therapy is allowed, but at least 12 months must have elapsed since completing CDK4/6 therapy and enrolling into ctDNA surveillance on this study. Participants in the PENELOPE and PALLAS clinical trials who received Palbociclib are also eligible if meet all required eligibility criteria. For screening, patients will undergo Signatera testing during routine follow up clinic visits. The current ASCO/NCCN breast cancer practice guidelines recommend follow up visits every 4 to 6 months at the treating physician's discretion. We anticipate that screening positivity rates will be the highest in patients between years 1-5 after initial diagnosis, based on the annual hazard rates of recurrence in ER positive breast cancer. However, since up to 50% of all recurrences occur after 5 years of follow-up, we allow starting ctDNA screening up to 7 years after starting adjuvant endocrine therapy if a patient meets criteria for high risk. Randomized phase II (N=100): Patients who become ctDNA positive during ctDNA surveillance will have systemic staging with CT of the chest, abdomen and pelvis, and those without radiographic evidence of metastatic disease will be randomized 1:1 to receive palbociclib plus fulvestrant for two years or continue standard of care endocrine therapy. Pre- and peri- menopausal patients randomized to the fulvestrant palbociclib arm will require GnRH analogue therapy. Patients in both treatment arms may continue adjuvant bisphosphonate therapy and patients in the control arm may switch between different brands of aromatase inhibitors for better tolerance or patient preference. No other, non-protocol directed anticancer therapy is allowed. The maximum duration of treatment is 2 years. A patient may complete a maximum of 26 cycles of treatment (for patients without interruptions or delays). The goal is not to administer a specific number of cycles, but to allow for the completion of any cycles initiated prior to 2 years from randomization. Patients who have completed 2 years of fulvestrant and palbociclib without recurrence may resume their originally planned standard of care adjuvant therapy to complete a total of 5 or 10 years of endocrine therapy at the discretion of the treating physician.

Efficacy of Daromun Neoadjuvant Intratumoral Treatment in Clinical Stage IIIB/C Melanoma Patients

The present study is an open-label, randomized, controlled, two-arm multi-center study of the efficacy of Daromun neoadjuvant intratumoral treatment followed by surgery and adjuvant therapy versus surgery and adjuvant therapy in clinical stage III B/C melanoma patients. 186 patients will be randomized in a 1:1 ratio to receive Daromun treatment followed by surgery and adjuvant therapy (Arm 1) or surgery and adjuvant therapy (Arm 2). In both arms, follow-up for assessing recurrence-free survival will be performed up to five years after randomization. Survival information will also be collected in the following year (up to six years in total after randomization). This is an open-label study, so there is no blinding. Patients who successfully complete the screening evaluations and are eligible for participation in the study will be enrolled and randomly assigned (1:1) to two parallel treatment arms: Daromun plus surgery and adjuvant therapy (Arm 1) or surgery and adjuvant therapy (Arm 2). To ensure a balance across treatment groups, stratified randomization with permuted block will be used and separate randomization list for each subgroup (stratum) will be produced. Patients will be stratified on the basis of the following prognostic factors: - Stage of disease (2 levels): Stage IIIB vs. Stage IIIC - Planned post-surgical adjuvant therapy (2 levels): anti-PD-1 and other adjuvant therapies. The primary objective of the study is to demonstrate that a neoadjuvant Daromun treatment followed by surgery and adjuvant therapy improves in a statistically significant manner the recurrence-free survival (RFS) of Stage IIIB/C melanoma patients with respect to the standard of care (surgery and adjuvant therapy). Primary endpoint of the study is RFS in a time-to-event analysis in the Daromun plus surgery and adjuvant therapy treatment group (Arm 1) versus the surgery plus adjuvant therapy control group (Arm 2). Analysis will be based on the "Intention To Treat" population. The key secondary objective of the study is to demonstrate that a neoadjuvant Daromun treatment followed by surgery and adjuvant therapy improves in a statistically significant manner the overall survival (OS) of patients with resectable Stage IIIB/ or C melanoma patients with respect to the standard of care (surgery and adjuvant therapy). For patients enrolled in both arms, local approved post-surgery adjuvant therapies (as part of the standard of care) are allowed and decided at the investigator's discretion. These include high-dose interferon- α2b, anti-CTLA-4 antibodies (e.g. Ipilimumab), anti-PD1 antibodies (e.g. Nivolumab, Pembrolizumab), targeted therapies (e.g. Dabrafenib + Trametinib), or other new local approved treatments.

Intermediate Risk Cervical Cancer: Radical Surgery +/- Adjuvant Radiotherapy

The role of adjuvant (chemo)radiotherapy in intermediate risk (IR) cervical cancer patients is controversial, supported by single randomised GOG 92 study performed more than 20 years ago. Intermediate-risk group is defined as lymph node negative but with a combination of negative prognostic factors (tumour size >2 cm, lymphovascular space invasion, deep stromal invasion >2/3). Recent retrospective studies showed excellent local control in intermediate risk group patients after radical surgery with no additional adjuvant treatment. CERVANTES trial is designed to bring level A evidence on the role of adjuvant treatment in IR patients in an international, prospective, randomised study. Patients will be registered into the trial before surgery and randomised after the final pathology report has been received into ARM A, with no additional treatment, and ARM B, receiving adjuvant (chemo)radiotherapy. Quality assurance program will be in place for both, radical surgery and adjuvant treatment.

Adjuvant Radioimmunotherapy Compared With Adjuvant Chemotherapy for UTUC

This study is an ambispective cohort observational study to analyze the efficacy of adjuvant radioimmunotherapy (radiotherapy and immunotherapy) compared with adjuvant chemotherapy in patients with the upper urinary tract urothelial carcinoma with high-risk factors (postoperative pathology suggestive of pT2 and above, N+, G3/high-grade and multiple tumors, positive cut margins). A subgroup analysis was performed to obtain the population of patients who might benefit from different treatment approaches. Patients with high risk factors for postoperative recurrence or metastasis will be treated with relevant adjuvant therapy, which in turn will benefit patients.

Clinical Study of Personalized mRNA Vaccine Encoding Neoantigen in Subjects With Resected Digestive System Neoplasms

This is a single-center, open-label, single-arm clinical study of personalized mRNA vaccine iNeo-Vac-R01 in combination with standard adjuvant therapy in subjects with surgically resected digestive system neoplasms.

PROfiling Based Endometrial Cancer Adjuvant Therapy

Adjuvant therapy for women with endometrial cancer has increasingly been tailored to prognostic factors to prevent overtreatment and select those women for adjuvant treatment who will have a clinically relevant reduction of the risk of relapse by the adjuvant treatment. Risk profiles have traditionally been based on clinicopathological factors such as age, stage, grade, Lymph-Vascular Space Invasion (LVSI) and depth of invasion. Newer, both molecular-genetic (the cancer genome atlas subgroups) have become available which are strongly related to outcomes and risk of cancer spread. Based on 2022 National Comprehensive Cancer Network (NCCN) guideline and the ongoing "Portec-4a" trial, this randomized trial using integrated genomic-pathologic classification to assign adjuvant treatment for women with stage I-II high-intermediate and intermediate risk endometrioid adenocarcinoma.

Oocyte Recovery During Tamoxifen Adjuvant Therapy

New chemotherapy regimens and management options developed during the last 20 years have yielded increased survival rates in cancer patients but they also cause side effects such as premature ovarian failure and infertility due to their gonadotoxicity. Hormone therapy also increases survival rates in breast cancer patients; tamoxifen, a selective estrogen receptor modulator, has been proven to reduce the risk of recurrence and mortality due to breast cancer when administered during 10 years. The risk of premature ovarian failure depends not only on the gonadotoxicity of chemotherapy but also on the age of the patient, therefore although tamoxifen is not gonadotoxic itself, it can compromise fertility because of the long length of treatment and the subsequent delay in childbearing. On the other hand, tamoxifen is a drug that can be used in assisted reproduction techniques to induce ovarian stimulation, therefore, the tamoxifen treatment followed by breast cancer patients represent somehow a way of continuous ovarian stimulation. If viable oocytes could be retrieved during the long-term hormonal treatment with tamoxifen, there will be an option to use them to restore fertility afterwards. STUDY DESIGN: Patients included in the study who have normal menstrual periods will be monitored by sonography (antral follicle count) and serum hormonal levels: E2 (oestradiol), P4 (progesterone), FSH (follicle stimulating hormone) and LH (luteinizing hormone) from the second day of their cycle. Patients without spontaneous menstruations will perform periodic visits every 15 days until images corresponding with antral follicle definition will be seen, this will be considered day 2 of the cycle. Follow-up of the antral follicles will be done with sonography and serum hormonal levels according to the protocols of the investigators in vitro fertilization unit. When a follicle of more than 18 mm is seen, 250 µg of hCG (human chorionic gonadotropin) will be administered and 36 hours after, transvaginal oocyte retrieval will be performed. Oocyte and embryo quality assessment will be performed according to morphological ASEBIR (association for the study of reproduction biology) classification on day +2 and +3. Grade 1 and 2 embryos on day +3 will be cryopreserved. Patients requiring assisted reproduction technologies to get pregnant after completion of their oncologic treatment will have their embryos thawed and subsequently transferred. FOLLOW-UP: During the time oocytes retrieved are being used or until the end of gestation in case the patient become pregnant. Bearing in mind that most of the patients in our center undergo 5 year of tamoxifen treatment, it will be assumed a maximum follow-up of 6 years.

Fexofenadine As Adjuvant Therapy in Parkinson Disease