Patients with previously untreated carcinoma of unknown primary MedDRA version: 13.1 Level: LLT Classification code 10007460 Term: Carcinoma of unknown primary System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Topotarget A/S
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Patients with carcinoma of unknown primary where the primary site had not been revealed by complete history, physical examination (including gynecological examination when appropriate), computed tomography 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. 2.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" do not fulfill the criteria for inclusion, unless immunohistochemical staining confirms the diagnosis of carcinoma. 3.Signed consent of an IRB/Ethics committee approved informed consent form. 4.At least one measurable lesion according to RECIST criteria. Note, target lesions can only be selected within previously irradiated areas if newly arising or clearly progressing after irradiation as proven by repeat scanning. 5.Performance status (ECOG) = 2. 6.Age =18 years. 7.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. 8.Serum potassium within normal range. 9.Acceptable coagulation status: PT or INR, and APTT = 1.5 x upper limit of normal (ULN) or in the therapeutic range if on anticoagulation therapy. 10.Acceptable liver, renal and bone marrow function including the following: • Bilirubin = 1.5 times ULN (if liver metastases are present, then = 3 x ULN is allowed) • AST (SGOT), and ALT (SGPT), and Alkaline Phosphatase = 3 times ULN (if liver metastases are present, then = 5 x ULN is allowed) • An estimated creatinine clearance = 45 mL/min using an appropriate formula (see Section 13.3), or measured EDTA renal clearance = 45 mL/min • Absolute neutrophils count = 1.5 x 109/L, platelets = 100 x 109/L • Hemoglobin = 9.0 g/dL or = 5.6 mmol/L (patients with chronic anemia due to underlying disease and its treatment may undergo blood transfusion prior to treatment in order to meet this criteria) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 55 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 34
Exclusion criteria
Exclusion criteria: 1.Patient with well recognized subsets of carcinoma of unknown primary 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 or progesterone receptor (ER/PR) • young men ( 450 msec; Long QT Syndrome; the required use of concomitant medication that may cause Torsade de Pointes (See Section 13.2, Appendix B). 8.Altered mental status precluding understanding of the informed consent process and/or completion of the necessary study procedures. 9.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. 10.Known hypersensitivity to either platinum compounds or paclitaxel, or any components of the study medications, and inability for desensitization. 11.Known infection with HIV, or known active Hepatitis B or C infection. 12.Peripheral neuropathy = Grade 2. 13.Pregn
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To provide an estimate of the hazard ratio of treatment effect when the combination of belinostat plus carboplatin and paclitaxel (BelCaP) is compared with the combination of carboplatin and paclitaxel in terms of progression-free survival for patients with carcinoma of unknown primary site. ;Secondary Objective: •To evaluate and compare further efficacy parameters (overall survival, objective response rate according to RECIST criteria, time to response, duration of response, and time to progression) in the randomized treatment groups receiving belinostat plus carboplatin and paclitaxel (BelCaP) or the combination of carboplatin and paclitaxel. •To evaluate and compare the safety profiles of the same randomized treatment groups using the NCI-CTC (version 3.0). ;Primary end point(s): The primary efficacy study variable is Progression Free Survival (PFS). This is defined as the time from the date of randomization to the day of documented disease progression or death due to any cause. It will be based on tumor assessments made according to the RECIST criteria. All tumor assessments obtained during the study, i.e. both treatment phase and follow-up phase, will be included in this analysis.;Timepoint(s) of evaluation of this end point: 2011 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall survival objective response rate according to RECIST criteria time to response duration of response time to progression;Timepoint(s) of evaluation of this end point: 2012 | — |
Countries
Denmark, France, Germany, United States
Contacts
Public ContactClinical Operations
Topotarget A/S
Outcome results
None listed