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

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

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.

Study Overview

• Status: Completed
• Conditions: Unknown Primary Tumors
• Intervention / Treatment: Drug: Gemcitabine; Drug: Carboplatin; Drug: nab-paclitaxel

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).

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Filippo MONTEMURRO, MD; Phone Number: 3250 011 993; Email: filippo.montemurro@ircc.it
• Study Contact Backup: Name: Elena Geuna, MD; Phone Number: 3250 011 993; Email: elena.geuna@ircc.it

Study Locations

• Italy
  • Bologna, Italy
    • AOU Policlinoco S Orsola - Malpighi
  • Genova, Italy
    • Ospedali Galliera
  • Milano, Italy
    • Istituto Nazionale dei Tumori
  • Milano, Italy
    • Ospedale Niguarda Cà Granda
  • Milano, Italy
    • Istituto Europeo Di Oncologia - IEO
  • Padova, Italy
    • Istituto Oncologico Veneto - IOV
  • Pavia, Italy
    • Fondazione IRCCS Policlinico San Matteo
  • Roma, Italy
    • Policlinico Universitario Campus Biomedico
  • Torino, Italy, 10126
    • A.O.U S.Giovanni Battista
  • Turin
    • Candiolo, Turin, Italy, 10060
      • Investigative Clinical Oncology (Oncologia Medica 2)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; 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.	Drug: Gemcitabine; Drug: nab-paclitaxel; Other Names: Abraxane
Experimental: Arm B; 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.	Drug: Carboplatin; Drug: nab-paclitaxel; Other Names: Abraxane

What is the study measuring?

Primary Outcome Measures

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 Measures

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

Collaborators and Investigators

• Sponsor: Fondazione del Piemonte per l'Oncologia

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Actual): May 4, 2021
• Study Completion (Actual): January 31, 2022

Study Registration Dates

• First Submitted: November 16, 2015
• First Submitted That Met QC Criteria: November 16, 2015
• First Posted (Estimated): November 17, 2015

Study Record Updates

• Last Update Posted (Actual): January 26, 2024
• Last Update Submitted That Met QC Criteria: January 25, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis; Neoplasms, Unknown Primary; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Carboplatin; Paclitaxel; Gemcitabine
• Other Study ID Numbers: 008-IRCC-10IIS-14