Treatment Guided by Comprehensive Genome and Transcriptome Analysis Versus Standard of Care in Advanced Rare Cancers

Inclusion Criteria: * Age ≥ 18years, no upper age limit * Patients with locally advanced and/or metastatic rare epithelial or mesenchymal cancer (equal numbers of patients) without curative treatment option * Progressive disease or expected progression of the disease estimated by clinical parameters, suitable biomarkers, and other (e.g. radiographic) methods \* At least one measurable lesion that has been accurately assessed by computed tomography (CT) or magnetic resonance imaging (MRI) at baseline and is amenable to repeat evaluation in MRI/CT images * Patients must have received at least one standard therapy for advanced disease according to current guidelines or consensus recommendations or have no standard therapy available * Possibility to perform fresh tumor biopsy according to local SOPs or Availability of fresh frozen tumor samples with sufficient tumor cell content collected within 3 months prior to enrolment * ECOG PS ≤ 2. * Ability of patient to understand character and consequences of the clinical trial * Patient must be willing and able to undergo subsequent treatment (e.g. in a clinical trial) with molecularly guided therapy according to the MTB recommendation * Availability of complete information about all medical treatment given before study participation, i.e. remission status before start of treatment, dosage and timing of drugs applied, remission status and date of progression after treatment Exclusion Criteria: * Dementia or significant cognitive impairment * Epilepsy requiring pharmacologic treatment * Prior allogeneic bone marrow or solid organ transplantation * Hematological malignancies and primary brain tumors. * Prior comprehensive molecular profiling by WGS, WES, RNA-Seq, or large targeted panels. * Patients with symptomatic or uncontrolled brain metastases and patients with symptomatic or uncontrolled spinal cord compression. Patients with previously treated brain metastases are eligible, provided that the patient has neither experienced a seizure nor had a clinically significant change in neurological status within the three months prior to enrollment. All patients with previously treated brain metastases must be clinically stable for at least 1 month after completion of treatment and off steroid treatment for one month, both prior to study enrollment. * Malignancy other than study indication within the last 5 years except: curatively treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), Stage 1, grade 1 endometrial carcinoma, low-risk prostate cancer, or other malignancies curatively treated with no evidence of disease for ≥5 years. * History of intracranial hemorrhage or spinal cord haemorrhage; no ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted * Known uncontrolled or significant cardiovascular disease, including any of the following: * History of heart failure NYHA class 3 or 4 * History of uncontrolled angina pectoris, arrhythmias, or myocardial infarction within 12 months prior to screening. * History of liver cirrhosis * Neurologic or psychiatric disorder interfering with ability of giving informed consent. * Known or suspected active alcohol or drug abuse. * Patients with inability to receive oral medications. * Failure to provide consent for the registration, storage, and processing of individual disease characteristics and clinical course, as well as for informing the primary care physician about the participant's involvement in the study.