Clinical trial NCT02607202: A Study of Nab-paclitaxel-based Doublet as First Line Therapy in Patients With Cancer of Unknown Primary (CUP)
Official title: A Phase II, Randomized, Multicenter Study to Assess the Efficacy of Nab-paclitaxel-based Doublet as First Line Therapy in Patients With Cancer of Unknown Primary (CUP): The AGNOSTOS Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Unknown Primary Tumors
Lead sponsor: Fondazione del Piemonte per l'Oncologia
Sponsor class: OTHER
First posted: 2015-11-17
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Objective response rate (ORR) as evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines.
timeFrame: 42 months
Secondary outcomes:
measure: duration of response according to RECIST version 1.1.
timeFrame: 42 months
measure: time to progression
timeFrame: 42 months
measure: overall survival
timeFrame: 42 months
measure: toxicity according to Common Terminology Criteria for Adverse Events - CTCAE version 4.03.
timeFrame: 42 months
Other outcomes:
Locations:
city: Candiolo
country: Italy
facility: Investigative Clinical Oncology (Oncologia Medica 2)
state: Turin
city: Bologna
country: Italy
facility: AOU Policlinoco S Orsola - Malpighi
city: Genova
country: Italy
facility: Ospedali Galliera
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia - IEO
city: Milano
country: Italy
facility: Istituto Nazionale dei Tumori
city: Milano
country: Italy
facility: Ospedale Niguarda Cà Granda
city: Padova
country: Italy
facility: Istituto Oncologico Veneto - IOV
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Roma
country: Italy
facility: Policlinico Universitario Campus Biomedico
city: Torino
country: Italy
facility: A.O.U S.Giovanni Battista
Study officials:
References: