a study of nab-paclitaxel-based doublet as first line therapy in patients with cancer of unknown primary (cup)

Conditions: Unknown Primary Tumors

Summary: agnostos trial is a multicentric phase 2 randomized trial with a 'pick-the-winner design' in chemonaive patients with cancer of unknown primary. it will assess the efficacy of the two best active single agent - carboplatin or gemcitabine - added to an innovative taxane back bone (nab-paclitaxel). agnostos trial is a part of a larger clinical and translational initiative to improve the outlook of patients with cancer of unknown primary through evaluation of novel chemotherapeutic regimens.

treatment-naïve patients with cup diagnosis confirmed according to cup diagnostic guidelines, will be enrolled into agnostos trial. patients will be randomized upfront to receive a nab-paclitaxel-based duplet adding either carboplatin or gemcitabine until progression or unacceptable toxicity (randomization 1:1, n= 120; 60 per arm).

Eligibility criteria:
inclusion criteria: * provision of written informed consent. * patients must be ≥ 18 years of age. * diagnosis of cup according to cup diagnostic guidelines derived from esmo 2011 and nccn 2015 guidelines. * sufficient archived biopsy tissue from a surgical or core needle biopsy required to perform the cup multiplex assay. * eastern cooperative oncology group performance status ≤ 2. * no previous systemic therapy. * at least one measurable lesion by recist criteria. * good liver, cardiac, lung and marrow bone function. * evidence of non-childbearing status for female patients: negative urine or serum pregnancy test within 21 days of study treatment for women of childbearing potential, or postmenopausal status. * patients of child bearing potential and their partners, who are sexually active, must agree to the use of highly effective forms of contraception throughout their participation in the study. * patient is willing and able to comply with the protocol for the duration of the study, including undergoing treatment and scheduled visits and examinations. exclusion criteria: * patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, breast ductal carcinoma in situ (dcis), stage 1 grade 1 endometrial carcinoma. * specific treatable cup syndromes including: extragonadal germ cell syndrome; neuroendocrine carcinoma; adenocarcinoma isolated to axillary lymph nodes (women cancer); peritoneal carcinomatosis (women - ovarian cancer); squamous carcinoma limited to cervical, supraclavicular, or inguinal lymph nodes; single resectable metastasis. * patients receiving any radiotherapy (except for palliative reasons), within 2 weeks from the last dose prior to study entry. * patients with symptomatic uncontrolled brain metastases. * major surgery within 2 weeks of starting the study and patients must have recovered from any effects of any major surgery. * patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 6 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent. * pregnant or breast feeding women. * immunocompromised patients, eg, patients who are known to be serologically positive for human immunodeficiency virus (hiv). * patients with known hepatic disease (eg, hepatitis b or c). * previous cancer treatment. * patients currently enrolled in another clinical tria, except agnostos profiling. * patients that are receiving chemotherapy, hormonal therapy (hrt is acceptable) or other novel agents. * patients receiving live virus and bacterial vaccines.