A Study of Nab-paclitaxel-based Doublet as First Line Therapy in Patients With Cancer of Unknown Primary (CUP)

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

Sponsors

Lead Sponsor: Fondazione del Piemonte per l'Oncologia

Source Fondazione del Piemonte per l'Oncologia
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).

Overall Status Unknown status
Start Date March 2015
Completion Date December 2018
Primary Completion Date September 2018
Phase Phase 2
Study Type Interventional
Primary Outcome
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 Outcome
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
Enrollment 120
Condition
Intervention

Intervention Type: Drug

Intervention Name: nab-paclitaxel

Other Name: Abraxane

Intervention Type: Drug

Intervention Name: Carboplatin

Arm Group Label: Arm B

Intervention Type: Drug

Intervention Name: Gemcitabine

Arm Group Label: Arm A

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.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Contact

Last Name: Filippo MONTEMURRO, MD

Phone: 011 993

Phone Ext.: 3250

Email: [email protected]

Location
Facility: Status: Contact: Contact Backup:
Investigative Clinical Oncology (Oncologia Medica 2) | Candiolo, Turin, 10060, Italy Recruiting Filippo Montemurro, MD 011993 3250 [email protected]
AOU Policlinoco S Orsola - Malpighi | Bologna, Italy Not yet recruiting Andrea Ardizzoni, MD
Ospedali Galliera | Genova, Italy Not yet recruiting Alessandra Gennari, MD
Istituto Europeo di Oncologia - IEO | Milano, Italy Not yet recruiting Giuseppe Curigliano, MD
Istituto Nazionale dei Tumori | Milano, Italy Not yet recruiting Filippo De Braud, MD
Ospedale Niguarda Cà Granda | Milano, Italy Not yet recruiting Salvatore Siena, MD
Istituto Oncologico Veneto - IOV | Padova, Italy Not yet recruiting Vittorina Zagonel, MD
Fondazione IRCCS Policlinico San Matteo | Pavia, Italy Not yet recruiting Giulia Stella, MD
Policlinico Universitario Campus Biomedico | Roma, Italy Not yet recruiting Giuseppe Tonini, MD
A.O.U S.Giovanni Battista | Torino, 10126, Italy Not yet recruiting Libero Ciuffreda, MD Libero Ciuffreda, MD Principal Investigator
Location Countries

Italy

Verification Date

August 2017

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Arm A

Type: Experimental

Description: nab-paclitaxel 125 mg/m2 on Days 1 and 8 by IV administration over 30 minutes without premedication, followed by gemcitabine 1000 mg/m2 on Days 1 and 8 by IV administration over 30 minutes. Treatment to be repeated Q21 days.

Label: Arm B

Type: Experimental

Description: nab-paclitaxel 125 mg/m2 on Days 1 and 8 by IV administration over 30 minutes without premedication, followed by carboplatin AUC 2 on Day 1 and 8 by IV administration over 60 minutes. Treatment to be repeated Q21 days.

Acronym AGNOSTOS
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov