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

Lead Sponsor: Fondazione del Piemonte per l'Oncologia

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.

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).

• Unknown Primary Tumors

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

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

Last Name: Filippo MONTEMURRO, MD

Phone: 011 993

Phone Ext.: 3250

Email: [email protected]

Italy

August 2017

Type: Sponsor

• Neoplasms, Unknown Primary

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.

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: None (Open Label)