A Phase I/II Study of Paclitaxel Plus Carboplatin Plus Vorinostat in Recurrent Ovarian Cancer

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2008 by Herlev Hospital.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Odense University Hospital
Information provided by:
Herlev Hospital
ClinicalTrials.gov Identifier:
NCT00772798
First received: October 14, 2008
Last updated: NA
Last verified: October 2008
History: No changes posted
  Purpose

TITLE:A Phase II non-comparative study of paclitaxel plus carboplatin in combination with Vorinostat in patients with advanced, recurrent epithelial ovarian cancer. INDICATION:Second-line treatment of patients with recurrent platinum-sensitive epithelial ovarian cancer. RATIONALE:Recurrent epithelial ovarian cancer is today an incurable disease. The current standard of care consists of systemic chemotherapy using either carboplatin plus paclitaxel (in platinum-sensitive patients) or single agent chemotherapy with agents like liposomal doxorubicin, topotecan, weekly paclitaxel or gemcitabine (platinum non-sensitive patients). The outcome for patients with advanced ovarian cancer nevertheless remains poor.Preclinical evidence suggests that vorinostat, a potent histone deacetylase (HDAC) inhibitor, may potentiate the antitumor activity of paclitaxel and/or carboplatin. The study will assess whether the addition of vorinostat to paclitaxel plus carboplatin is manageable and induces reasonable response rates in patients with advanced recurrent, platinum-sensitive ovarian cancer. Biomarkers will be collected from both primary tumors and biopsies before and after start of treatment with vorinostat.

DESIGN:Phase II, single-center study. All eligible patients will be treated with intravenous paclitaxel plus carboplatin plus oral vorinostat. Patients will be treated with a maximum of 6 cycles or until disease progression, unacceptable toxicity or withdrawal of consent. Clinical endpoints will include adverse experiences, progression-free survival (PFS) and response rate (RR). SAMPLE:Patients must have a histologically confirmed diagnosis of epithelial ovarian cancer, cancer of the Fallopian tube or primary peritoneal adenocarcinoma. All patients will have received first-line therapy with carboplatin plus paclitaxel. Patients should be platinum sensitive, defined as recurrence or progression of ovarian cancer, cancer of the Fallopian tubes or primary peritoneal adenocarcinoma 6 months or later after the end of first-line chemotherapy. Patients to be enrolled on this study must have acceptable performance status and acceptable renal and hepatic function, and be free of other serious intercurrent illness that could impair their ability to receive protocol therapy. The study will include up to 55 assessable patients, of which 20 will provide biomarkers. It is estimated that the inclusion period will last approximately 24 months. DOSAGE/DOSAGE FORM, ROUTE, AND DOSE REGIMEN Eligible patients will be treated with paclitaxel (175 mg/m2) and carboplatin AUC5 administered by intravenous infusion (IV) on day 1 of each treatment cycle. In addition, all eligible patients will receive treatment with oral vorinostat (400 mg) administered once daily by mouth with food on days -4 through 10 of Cycle 1 (25-day treatment cycle) and days 1 through 14 of each subsequent 21-day treatment cycle. Patients will receive antiemetic therapy according to institutional guidelines as well as premedication with dexamethasone, and antihistamines (an H1-receptor antagonist and an H2-receptor antagonist) for prevention of the side effects of paclitaxel.


Condition Intervention Phase
Ovarian Cancer
Drug: Paclitaxel, Carboplatin and Vorinostat
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Non-Comparative Study of Paclitaxel Plus Carboplatin in Combination With Vorinostat in Patient With Advanced, Recurrent, Epithelial Ovarian Cancer

Resource links provided by NLM:


Further study details as provided by Herlev Hospital:

Primary Outcome Measures:
  • Primary: To assess the objective response rate, safety, tolerability, and adverse experience profile of vorinostat administered in combination with paclitaxel plus carboplatin in patients with platin sensitive recurrent epithelial ovarian cancer. [ Time Frame: Until disease progression ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To determine the progression-free survival (PFS) of patients with advanced, recurrent epithelial ovarian cancer, cancer of the Fallopian tube or primary peritoneal adenocarcinoma treated with paclitaxel plus carboplatin and vorinostat. [ Time Frame: Until progression of disease ] [ Designated as safety issue: No ]

Estimated Enrollment: 70
Study Start Date: June 2007
Estimated Study Completion Date: June 2009
Estimated Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Paclitaxel, Carboplatin and Vorinostat
    Intravenous paclitaxel (175 mg/m2) and carboplatin (AUC 5) and oral vorinostat 400 mg day 1-14 every three weeks.
    Other Names:
    • Taxol
    • Carboplatin
    • Vorinostat
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histological verified epithelial carcinoma derived from ovarian, peritoneum or uterine tubes
  2. Women ≥18 years old.
  3. ECOG performance status ≤2.
  4. Expected duration of life >3 months.
  5. Previous treatment regimen containing platinum and paclitaxel.
  6. Platinum and paclitaxel sensitive tumor, defined as a minimum of 6 months from cessation of treatment until disease progression.
  7. Measurable or assessable lesion.Patients having increased CA-125 as the only sign of recurrence are also eligible.
  8. Normal organ functions defined by the following values:

    Absolute neutrophil count (ANC) ≥1,500/µL Platelets ≥100,000/µL Hemoglobin ≥9.0g/dL or > 5.7 mmol/L CA125 0-35 Glomerular filtration rate (GFR) measured using Cr-EDTA clearance GFR ≥50 mL/minute (not corrected for body surface area) Serum Total bilirubin ≤1.5 times the ULN AST (SGOT) and ALT (SGPT) ≤2.5 times the ULN Alkaline phosphatase ≤5.0 times the ULN Prothrombin time (PT) ≤1.2 times the ULN unless the patient is receiving therapeutic anticoagulation.

    Partial thromboplastin time (PTT) ≤1.2 times the ULN unless the patient is receiving therapeutic anticoagulation.

  9. Signed informed consent before inclusion.
  10. Prepared to appear for the planned follow-up visits and capable of handling toxicity.

Exclusion Criteria:

  1. Patients treated with an experimental drug within the last 4 weeks before inclusion, and patients who receive other concomitant anticancer treatment.
  2. Patients having an active infection, or who have received intravenous antibacterial or antifungal medicine within the last 2 weeks before inclusion.
  3. Patients previously treated with an HDAC inhibitor. Patients, who have been treated with Valproate for convulsions can be included, however only if the treatment has taken place > 30 days before inclusion.
  4. Patients treated with steroid, who are not stabilized on a firm dose equivalent to a maximum of 10 mg prednisolone per day for the last 4 weeks before inclusion.
  5. Previous treatment with more than first-line chemotherapy.
  6. Progression during treatment with first-line chemotherapy containing platin/paclitaxel or disease progression less than 6 months after treatment cessation.
  7. Concomitant serious and/or non-controllable medical condition such as non-controllable infection (including HIV infected patients), hypertension, ischemic heart disease, myocardial infarction within the last 6 months, congestive heart failure.
  8. Previous treatment for, or other concomitant malignant disease within the last 5 years, except for curative treated carcinoma in situ cervical cancer or basal cell carcinoma.
  9. Previous severe allergic reactions in connection with carboplatin, paclitaxel or agents within the histone deacetylase inhibitor group.
  10. Women of child-bearing age. Women must have undergone surgical removal of the ovaries or be post-menopausal with no menstruation during the previous year.
  11. Peripheral neuropathy ≥ grade 2, unless this is due to a medical condition.
  12. Patients with history of severe hyper sensitive reactions with regards to products containing Cremophor EL (cyclosporine or K-vitamin) and/or patients with known hypersensitivity towards agents chemically connected to paclitaxel, carboplatin or vorinostat.
  13. Patients with known cerebral metastases or clinical signs of cerebral metastases.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00772798

Contacts
Contact: Jørn Herrstedt, professor +45 6541 3634 herrstedt@ouh.regionsyddanmark.dk
Contact: Hanne Havsteen, consultant +45 4488 2527 hahav@heh.regionh.dk

Locations
Denmark
Department of Oncology R Recruiting
Odense, Denmark, DK-5000 C
Sponsors and Collaborators
Herlev Hospital
Odense University Hospital
Investigators
Principal Investigator: Jørn Herrstedt, professor Odense University Hospital
  More Information

No publications provided

Responsible Party: Jørn Herrstedt, M.D., DMSCI, professor, dept. of oncology, Odense University Hospital, Sdr. Boulevard 29, DK-5000 C, Denmark
ClinicalTrials.gov Identifier: NCT00772798     History of Changes
Other Study ID Numbers: S9X
Study First Received: October 14, 2008
Last Updated: October 14, 2008
Health Authority: Denmark: Danish Medicines Agency

Keywords provided by Herlev Hospital:
ovarian cancer
HDAC inhibitor
vorinostat

Additional relevant MeSH terms:
Ovarian Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Adnexal Diseases
Genital Diseases, Female
Endocrine System Diseases
Gonadal Disorders
Vorinostat
Carboplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Histone Deacetylase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 21, 2014