Cisplatin Induction With Paclitaxel Consolidation for Stage III-IV Epithelial Ovarian and Primary Peritoneal Cancer

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by:
University of California, Irvine
ClinicalTrials.gov Identifier:
NCT00314678
First received: April 12, 2006
Last updated: December 7, 2007
Last verified: December 2007
  Purpose

Clinically, there has been extensive experience with topotecan and cisplatin. Recently, several investigators have evaluated the combination of paclitaxel, cisplatin and topotecan. As expected, myelosuppression was the dose-limiting factor. Herben et al recently reported the results of a phase I trial using the combination of paclitaxel, cisplatin, and topotecan as first line therapy in advanced stage ovarian cancer. Interestingly, the authors could not achieve a dose of topotecan that would be considered "optimal" for the treatment of relapsed disease in a single-agent fashion. The inability to utilize a therapeutic dose when combined with either platinum or paclitaxel has been demonstrated in previous reports and affirms the bone marrow suppressive effect. The clinical response rate from this trial was reported as 86.7%.


Condition Intervention Phase
Epithelial Ovarian Cancer
Primary Peritoneal Cancer
Drug: Topotecan
Drug: Cisplatin
Drug: Paclitaxel
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: Cisplatin Induction Followed by Paclitaxel Consolidation for the Treatment of Stage III and IV Epithelial Ovarian Cancer and Primary Peritoneal Cancer With In Vitro Correlates of Response

Resource links provided by NLM:


Further study details as provided by University of California, Irvine:

Primary Outcome Measures:
  • Recurrence-Free Interval

Secondary Outcome Measures:
  • Examine the toxicity of therapy and to develop suitable strategies for dose modification.

Estimated Enrollment: 40
Study Start Date: September 2005
Study Completion Date: April 2007
Detailed Description:

Malignant neoplasms of the ovary are the cause of more deaths than any other gynecologic cancer. Approximately 26,500 new cases are diagnosed each year in the United States, and about 14,500 deaths occur annually as a result of this disease. Clinicians continue to be frustrated by both the paucity of data concerning the etiologic factors in epithelial ovarian cancer and by the failure to achieve a significant reduction in mortality over the past several decades.

Since the introduction of cisplatin-based chemotherapy, no treatment has been shown to improve survival in subjects with advanced ovarian cancer until the incorporation of paclitaxel into primary therapy for this disease. In 1996, the Gynecologic Oncology Group (GOG) published the results of a large prospective, randomized trial of cisplatin and cyclophosphamide compared to cisplatin and paclitaxel. The cisplatin plus paclitaxel regimen was noted to be superior based on: 1) an overall improved response rate; 2) an increased clinical response rate (51% vs. 31%); 3) an increased rate of negative second look laparotomies; 4) an increase in median progression free survival; and importantly 5) an increased overall median survival (38 months vs. 24 months). The GOG results were recently confirmed by the Canadian- European consortium randomized phase III trial (OV 10).

These large randomized trials established the combination of paclitaxel and cisplatin as the standard, first line therapy for women with advanced ovarian cancer following cytoreductive surgery. Although the majority of women with advanced ovarian cancer will demonstrate an objective response to this combination; the response is generally of limited duration. The five-year survival for advanced stage ovarian cancer is 20-40%. Consequently, there remains a need for an improved chemotherapeutic approach in the management of ovarian cancer.

Topotecan is a semi-synthetic analog of camptothecin, a topoisomerase inhibitor. It has been investigated in a number of phase II trials as salvage therapy for recurrent ovarian cancer. Overall response rates have ranged from 6% to 27%. In a randomized comparative trial of topotecan versus paclitaxel, overall response rates were 21% and 14% respectively. The median survival for topotecan was 63 weeks as compared to 53 weeks for paclitaxel. Both drugs demonstrated higher response rates in platinum-sensitive tumors than platinum-resistant tumors. These data suggest that topotecan may be as active as paclitaxel, and partially non-cross resistant with cisplatin.

Topotecan may be a better agent than paclitaxel for use in combination with cisplatin for multiple reasons. First, Kern et al demonstrated that paclitaxel may antagonize the activity of cisplatin. Second, topotecan has been demonstrated to be synergistic with both cisplatin and paclitaxel in vitro. It has been demonstrated that topotecan can dramatically potentiate the effects of platinum, perhaps by its ability to inhibit repair of platinum-DNA adducts.

Clinically, there has been extensive experience with topotecan and cisplatin. Recently, several investigators have evaluated the combination of paclitaxel, cisplatin and topotecan. As expected, myelosuppression was the dose-limiting factor. Herben et al recently reported the results of a phase I trial using the combination of paclitaxel, cisplatin, and topotecan as first line therapy in advanced stage ovarian cancer. Interestingly, the authors could not achieve a dose of topotecan that would be considered "optimal" for the treatment of relapsed disease in a single-agent fashion. The inability to utilize a therapeutic dose when combined with either platinum or paclitaxel has been demonstrated in previous reports and affirms the bone marrow suppressive effect. The clinical response rate from this trial was reported as 86.7%.

  Eligibility

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

Eligible Subjects:

  1. Subjects with a histologic diagnosis of epithelial ovarian cancer or primary peritoneal carcinoma, stage III or IV, as outlined above. All subjects must have appropriate surgery for ovarian carcinoma with appropriate tissue for histologic evaluation and evaluated by the EDR assay.
  2. Eligible cell types include:

    Serous adenocarcinoma Endometrioid adenocarcinoma Mucinous adenocarcinoma Undifferentiated carcinoma Clear cell adenocarcinoma Mixed epithelial carcinoma Transitional cell carcinoma Malignant Brenner's Tumor

  3. Adequate bone marrow, renal, and hepatic function as defined by WBC3000cells/mcl, platelets 100,000/mcl, serum creatinine 2mg/dcl, bilirubin 1.5times normal, and SGOT 3 times normal.
  4. Subjects with GOG Performance Status of 0, 1, or 2.
  5. Subjects must have a complete history and physical examination done by the investigators of this study. Also, CBC with differential, electrolytes, serum creatinine, liver function tests and CA 125 must be done 14 days prior to registration.
  6. Subjects must be informed of the investigational nature of this study and must provide informed consent in accordance with institutional and federal guidelines.
  7. All subjects must have histologic slides available for pathology review.
  8. Subjects must be entered within six weeks of surgery.

Ineligible Subjects:

  1. Subjects with epithelial ovarian carcinoma of low malignant potential.
  2. Subjects who have received prior radiotherapy or chemotherapy.
  3. Subjects with septicemia, severe infection, or acute hepatitis.
  4. Subjects with severe gastrointestinal bleeding.
  5. Subjects with a GOG Performance Status of 3 or 4.
  6. Subjects with other invasive malignancies, with the exception of non-melanoma skin cancer, who had or have any evidence of other cancer within the last 5 years or whose previous cancer treatment contradicts this protocol therapy.
  7. Subjects who are pregnant will be excluded.
  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: NCT00314678

Locations
United States, California
Chao Family Comprehensive Cancer Center
Orange, California, United States, 92868
Sponsors and Collaborators
University of California, Irvine
GlaxoSmithKline
Investigators
Principal Investigator: John P Fruehauf, MD, PhD Chao Family Comprehensive Cancer Center
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00314678     History of Changes
Other Study ID Numbers: UCI 99-25
Study First Received: April 12, 2006
Last Updated: December 7, 2007
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, Irvine:
Ovarian
Peritoneal

Additional relevant MeSH terms:
Ovarian Neoplasms
Peritoneal Neoplasms
Neoplasms, Glandular and Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Neoplasms by Histologic Type
Cisplatin
Paclitaxel
Topotecan
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014