Belinostat, Carboplatin and Paclitaxel (BelCaP) Compared to Carboplatin and Paclitaxel in Patients With Cancer of Unknown Primary

Inclusion Criteria

• Patients with CUP where the primary site had not been revealed by complete history, physical examination (including gynecological examination when appropriate), computed tomography (CT) scan of the chest, abdomen and pelvis, bilateral mammography (in women with adenocarcinoma or poorly differentiated carcinoma), routine laboratory studies (complete blood cell counts, electrolytes, urinalysis, liver and renal function tests), and directed work-up of any other symptomatic areas.
• Light microscopic pathologic diagnosis of adenocarcinoma (including poorly differentiated), squamous cell carcinoma, or poorly differentiated carcinoma. Patients with poorly differentiated carcinoma must have immunohistochemical stains to confirm the diagnosis of carcinoma, and to rule out other tumor types. Note: patients with a light microscopic histology diagnosis of "poorly differentiated neoplasm, not otherwise classified" did not fulfill the criteria for inclusion, unless immunohistochemical staining confirmed the diagnosis of carcinoma.
• Signed consent of an IRB ([Institutional Review Board])/IEC ([Independent ethics committee]) approved ICF ([Informed Consent Form]).
• At least one measurable lesion according to RECIST ([response evaluation criteria in solid tumors ]) criteria. Note, target lesions could only be selected within previously irradiated areas if newly arising or clearly progressing after irradiation as proven by repeat scanning
• Performance status Eastern Cooperative Oncology Group (ECOG) ≤ 2.
• Age ≥ 18 years.
• A negative serum or urine pregnancy test for women of childbearing potential. Postmenopausal women must have been amenorrheic for ≥ 12 months to be considered of non-childbearing potential.
• Serum potassium within normal range.
• Acceptable coagulation status: Prothrombin time/International normalized ratio PT/INR ([international normalized ratio]), and activated partial thromboplastin time (APTT) ≤ 1.5 × upper limit of normal (ULN) or in the therapeutic range if on anticoagulation therapy.
• Acceptable liver, renal and bone marrow function including the following:
• Bilirubin ≤ 1.5 times ULN (if liver metastases were present, then ≤ 3 × ULN was allowed).
• Aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT), alanine amino transferase/serum glutamic pyruvic transaminase (ALT/SGPT), and alkaline phosphatase ≤ 3 times ULN (if liver metastases were present, then ≤ 5 × ULN was allowed).
• An estimated creatinine clearance ≥ 45 mL/min using an appropriate formula (Appendix C, protocol version 1.0, Appendix 16.1.1), or measured ethylenediaminetetraacetic acid (EDTA) renal clearance ≥ 45 mL/min.
• Absolute neutrophils count ≥ 1.5 × 109/L, platelets ≥ 100 × 109/L.
• Hemoglobin ≥ 9.0 g/dL or ≥ 5.6 mmol/L (patients with chronic anemia due to underlying disease and its treatment could undergo blood transfusion prior to treatment in order to meet this criteria).

Exclusion Criteria

• Patients with well recognized subsets of CUP site where treatments directed towards a defined tumor type, or surgery, alternatively radiotherapy, can be advised:
• Women with adenocarcinoma involving only axillary lymph nodes.
• Women with papillary serous carcinoma of the peritoneum.
• Women with adenocarcinoma with positive staining for estrogen receptor (ER) or progesterone receptor.
• Young men ( 450 millisecond (ms); Long QT Syndrome; the required use of concomitant medication that may cause Torsade de Pointes (Section 13.2, Appendix B, protocol version 1.0, Appendix 16.1.1).
• Altered mental status precluding understanding of the informed consent process and/or completion of the necessary study procedures.
• History of a previous malignancy within 5 years with the exception of non-metastatic non-melanoma skin cancer or cervical carcinoma in situ. Prior systemic therapy for other malignancy completed at least 5 years before randomization is allowed.

Implemented with amendment 2 (study cente