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

Study Overview
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Brief Summary
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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
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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).

Official Title
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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

Conditions
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Unknown Primary Tumors

Intervention / Treatment
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* Drug: nab-paclitaxel
* Drug: Carboplatin
* Drug: Gemcitabine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>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<br> <br> * Other names: Abraxane;Drug: Gemcitabine<br> <br> |
| Experimental: Arm B<br>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<br> <br> * Other names: Abraxane;Drug: Carboplatin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 |