An Open-label Randomized Phase II Trial of Belinostat (PXD101) in Combination With Carboplatin and Paclitaxel (BelCaP) Compared to Carboplatin and Paclitaxel in Patients With Previously Untreated Carcinoma of Unknown Primary
18 Years
N/A
Both
Occult Primary
Trial Information
An Open-label Randomized Phase II Trial of Belinostat (PXD101) in Combination With Carboplatin and Paclitaxel (BelCaP) Compared to Carboplatin and Paclitaxel in Patients With Previously Untreated Carcinoma of Unknown Primary
This is an open-label, multinational, multicenter, randomized, comparative efficacy and
safety study in previously untreated patients with carcinoma of unknown primary. Patients
meeting inclusion and exclusion criteria will be randomized to treatment within either of
two study groups:
- Group A: belinostat administered as a 30 minute IV infusion once daily on days 1, 2 and
3 followed by belinostat administered orally once daily on days 4 and 5, every 3-weeks,
in combination with paclitaxel administered as an IV infusion following the infusion of
belinostat on cycle day 3, and carboplatin administered as a 30-60 minute IV infusion
directly after the paclitaxel administration on cycle day 3.
- Group B: paclitaxel administered as an IV infusion directly followed by carboplatin
administered as a 30-60 minute IV infusion on cycle day 1 of a 3-weekly cycle.
Approximately 44 patients will be randomized to each group (in total 88 patients) over a
planned recruitment period of 15 months. Patients will be treated in three week cycles for
up to 6 cycles of chemotherapy containing treatment unless there is disease progression or
treatment-related toxicities that are not manageable with dose-reduction schemes allowed per
protocol or by other appropriate supportive measures. After 6 cycles of treatment, patients
in Group A will continue treatment on belinostat monotherapy administered orally once daily
on days 1 to 14, every 3-weeks until disease progression or treatment-related toxicities.
Toxicity will be monitored continuously during study treatment and 30 days following last
study drug administration. Safety will be assessed by adverse events and laboratory tests,
graded according to the NCI CTC (version 3.0).
Tumor assessments according to RECIST will be made by appropriate radiologic imaging
techniques at baseline and by the same techniques every 6 weeks for the initial 6 months,
then every 9 weeks for the next 6 months, then every 12 weeks for a further 12 months, and
then every 6 months until 5 years from the start of study treatment cycle 1. When tumor
assessments stop, survival follow-up will be carried out every 3 months for the initial 2
years, and then every 6 months until 5 years from the start of study treatment cycle 1.
Inclusion Criteria:
Include
- 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.
- Light microscopic pathologic diagnosis of adenocarcinoma (including poorly
differentiated), squamous cell carcinoma, or poorly differentiated carcinoma.
- Signed consent of an IRB/Ethics committee approved informed consent form.
- At least one measurable lesion according to RECIST criteria.
- Performance status (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.
- Acceptable liver, renal and bone marrow function.
Exclusion Criteria:
Include
- 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.
- 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.
- 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.
- Co-existing active severe infection or any co-existing medical condition assessed by
the investigator as likely to interfere with trial procedures.
- Significant cardiovascular disease
- 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.
- Known infection with HIV, or known active Hepatitis B or C infection.
- Peripheral neuropathy ≥ Grade 2.
- Pregnant, or lactating, females.
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Progression Free Survival measured by RECIST criteria
Outcome Time Frame:
May 2010
Safety Issue:
No
Principal Investigator
Seaborn Wade, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Virginia Cancer Institute - USA
Authority:
United States: Food and Drug Administration
Study ID:
PXD101-CLN-17
NCT ID:
NCT00873119
Start Date:
February 2009
Completion Date:
December 2012
Related Keywords:
- Occult Primary
- Belinostat
- PXD101
- Carboplatin
- Paclitaxel
- CUP
- Carcinoma of unknown primary
- Occult primary
- Carcinoma
- Neoplasms, Unknown Primary
Name | Location |
|---|---|
| South Texas Oncology and Hematology | San Antonio, Texas 78229 |
| Florida Cancer Specialists | Fort Myers, Florida 33901 |
| Research Medical Center | Kansas City, Missouri 64132 |
| South Carolina Oncology Associates | Columbia, South Carolina 29201 |
| Oncology Hematology Care Inc. | Cincinnati, Ohio 45242 |
| Virginia Cancer Institute | Richmond, Virginia 23230 |
| Northwest Georgia Oncology Centers | Marietta, Georgia 30060 |
| Chattanooga Oncology & Hematology Associates, PC | Chattanooga, Tennessee 37404 |
| Center for Cancers and Blood Disorders | Bethesda, Maryland 20817 |
| Tennessee Oncology Sarah Cannon Research | Nashville, Tennessee 37203 |
| Baton Rouge Medical Center | Baton Rouge, Louisiana 70809 |
