Unknown Primary Tumors
Conditions
Brief 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.
Detailed description
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).
Interventions
DRUGnab-paclitaxel
DRUGCarboplatin
DRUGGemcitabine
Sponsors
Fondazione del Piemonte per l'Oncologia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective response rate (ORR) as evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines. | 42 months |
Secondary
| Measure | Time frame |
|---|---|
| duration of response according to RECIST version 1.1. | 42 months |
| time to progression | 42 months |
| overall survival | 42 months |
| toxicity according to Common Terminology Criteria for Adverse Events - CTCAE version 4.03. | 42 months |
Countries
Italy
Outcome results
None listed