An open-label randomized phase II trial of belinostat (PXD101) in combination with carboplatin and paclitaxel (BelCaP) compared to carboplatin and paclitaxel in untreated patients with a cancer where the origin of the cancer cannot be established this special cancer is called carcinoma of unknown primary

• Conditions: Patients with previously untreated carcinoma of unknown primary; MedDRA version: 14.1Level: LLTClassification code 10007460Term: Carcinoma of unknown primarySystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2008-005865-67-DE
• Lead Sponsor: Topotarget A/S

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-12-11
• Last Update Posted: 16 February 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 89

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

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 (< 45 yrs old) with poorly differentiated carcinoma consistent with an extragonadal germ cell tumor (carcinoma involving mediastinium or retroperitonium, or elevated levels of beta-human chorionic gonadotropin or alpha-fetoprotein)
•men with bone metastases and/or adenocarcinoma, and abnormally elevated prostate specific antigen (PSA) in their plasma
•patients with squamous cell carcinoma involving only cervical lymph nodes, or inguinal lymph nodes
•patients with neuroendocrine carcinomas determined according to standard pathology diagnosis procedures, including stains
•patients with potentially completely resectable metastatic disease, or disease which can be adequately treated with radiotherapy only.
2.Patients with brain or meningeal metastases. Note, patients with adequately treated brain metastases, e.g. surgically resected, or adequately controlled by radiotherapy, with no residual neurological symptoms due to metastases and no steroid treatment required, can be enrolled. If clinical suspicion, adequate investigations should be performed to rule out brain metastases or meningeal involvement.
3.Prior systemic anti-tumor therapy, including chemotherapy administered in association to radiotherapy for sensitization, for the carcinoma of unknown primary. Note, prior radiotherapy or surgery is allowed provided treatment was completed at least 4 weeks before randomization.
4.Treatment with investigational agents, including non-anti-tumor agents, within the last 4 weeks before randomization.
5.Co-existing active severe infection or any co-existing medical condition assessed by the investigator as likely to interfere with trial procedures.
6.Significant cardiovascular disease (New York Heart Association Class III or IV cardiac disease), myocardial infarction within the past 6 months, unstable angina, unstable arrhythmia or a need for anti-arrhythmic therapy (use of medication to control heart rate in patients with atrial fibrillation is allowed, if stable medication for at least last month prior to randomization and medication not listed as causing Torsade de Points, see Section 13.2, Appendix B), or evidence of acute ischemia on ECG.
7.Marked baseline prolongation of QT/QTc interval, i.e., demonstration of a QTc interval > 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified