AGNOSTOS: A Study of Nab-paclitaxel-based Doublet as First Line Therapy in Patients With Cancer of Unknown Primary (CUP)
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
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 Design
Arms and Interventions
| 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: nab-paclitaxel
Other Names:
Drug: Gemcitabine
|
| 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: nab-paclitaxel
Other Names:
Drug: Carboplatin
|
Outcome Measures
Primary Outcome Measures
- Objective response rate (ORR) as evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines. [42 months]
Secondary Outcome Measures
- 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]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Provision of written informed consent.
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Patients must be ≥ 18 years of age.
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Diagnosis of CUP according to CUP Diagnostic Guidelines derived from ESMO 2011 and NCCN 2015 guidelines.
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Sufficient archived biopsy tissue from a surgical or core needle biopsy required to perform the CUP multiplex assay.
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Eastern Cooperative Oncology Group performance status ≤ 2.
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No previous systemic therapy.
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At least one measurable lesion by RECIST Criteria.
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Good liver, cardiac, lung and marrow bone function.
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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.
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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.
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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:
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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.
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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.
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Patients receiving any radiotherapy (except for palliative reasons), within 2 weeks from the last dose prior to study entry.
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Patients with symptomatic uncontrolled brain metastases.
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Major surgery within 2 weeks of starting the study and patients must have recovered from any effects of any major surgery.
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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.
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Pregnant or breast feeding women.
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Immunocompromised patients, eg, patients who are known to be serologically positive for human immunodeficiency virus (HIV).
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Patients with known hepatic disease (eg, Hepatitis B or C).
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Previous cancer treatment.
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Patients currently enrolled in another clinical tria, except AGNOSTOS PROFILING.
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Patients that are receiving chemotherapy, hormonal therapy (HRT is acceptable) or other novel agents.
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Patients receiving live virus and bacterial vaccines.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Investigative Clinical Oncology (Oncologia Medica 2) | Candiolo | Turin | Italy | 10060 |
| 2 | AOU Policlinoco S Orsola - Malpighi | Bologna | Italy | ||
| 3 | Ospedali Galliera | Genova | Italy | ||
| 4 | Istituto Europeo di Oncologia - IEO | Milano | Italy | ||
| 5 | Istituto Nazionale dei Tumori | Milano | Italy | ||
| 6 | Ospedale Niguarda Cà Granda | Milano | Italy | ||
| 7 | Istituto Oncologico Veneto - IOV | Padova | Italy | ||
| 8 | Fondazione IRCCS Policlinico San Matteo | Pavia | Italy | ||
| 9 | Policlinico Universitario Campus Biomedico | Roma | Italy | ||
| 10 | A.O.U S.Giovanni Battista | Torino | Italy | 10126 |
Sponsors and Collaborators
- Fondazione del Piemonte per l'Oncologia
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 008-IRCC-10IIS-14