Fragmin in Ovarian Cancer: Utility on Survival (FOCUS)

Ovarian Cancer Clinical Trial

Official title:

A Phase II Randomized Study of Fragmin in Ovarian Cancer: Utility on Survival (FOCUS)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00239980
• Other study ID #: NRA6300011-FOCUS-II
• Status: Completed
• Phase: Phase 2
• First received: October 13, 2005
• Last updated: February 2, 2010
• Start date: October 2005
• Est. completion date: January 2010

Study information

• Verified date: February 2010
• Source: Ontario Clinical Oncology Group (OCOG)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

Epithelial ovarian carcinoma (EOC) is the 5th leading cause of death among women. Long-term survival is poor for the majority of women with EOC because many present with advanced disease. Chemotherapy and cytoreductive surgery produces a 50% - 60% response rate but relapse is not uncommon. Adding more systemic agents has failed to show a clear benefit in survival and is associated with unacceptable toxicity. This phase II, dose-finding, open label trial will enrol women with newly diagnosed EOC and randomize them to receive one of 3 doses of a LMWH dalteparin in conjunction with standard adjuvant taxane- and platinum-based chemotherapy. The primary outcome is disease response, measured according to Gynaecologic Cancer Intergroup (GCIG) Cancer Antigen (CA)-125 response criteria. Secondary outcomes include symptomatic venous thromboembolism, bleeding, and compliance. The dose of dalteparin associated with the best response will be tested further in a phase III randomized clinical trial in the same patient population.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 77
• Est. completion date: January 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

Patients must meet all of the following criteria to be considered for enrolment:

• Women with newly diagnosed, histologically proven EOC are potentially eligible. Patients with primary peritoneal or fallopian tube tumours of equivalent histology are also considered for enrolment. If open or true cut biopsy is not available, fine needle aspiration (FNA) showing an adenocarcinoma is considered diagnostic for EOC if all 4 (a to d) of the following conditions are satisfied:

1. Patient has a pelvic mass, AND

2. Any evidence of disease larger than 1 cm in the upper abdomen (unless proven stage IV), AND

3. Normal mammography within 6 weeks of randomization, AND

4. Serum CA-125/CEA greater than or equal to 25. If the ratio is less than 25, a barium enema (or colonoscopy) and gastroscopy (or radiological examination of the stomach) must be negative for a primary tumour.

• Between the ages of 18 and 75.

• FIGO stage IIB to IV disease.

• A pre-study CA-125 level at least twice the upper limit of normal.

• Eligible for standard adjuvant treatment with taxane- and platinum-based chemotherapy by meeting all of the following laboratory findings within 7 days prior to randomization:

1. Absolute granulocyte count of at least 1.5 x 10 9/L (1500 per cubic millimetre).

2. Platelet count of at least 150 x 109/L (100,000 per cubic millimetre).

3. Serum creatinine no greater than 177 micromol/L (2.0 mg/dL).

4. Total bilirubin level no greater than 1.5 times the upper limit of normal at the local centre.

5. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) levels no greater than 3 times the upper limit of normal of the local centre.

Exclusion Criteria:

• Borderline ovarian tumours.

• Received prior chemotherapy or radiation therapy for EOC.

• Received mouse antibodies anytime during the 28 days prior to the pre-study CA-125 level.

• History of another malignancy, unless disease-free for 5 years or greater; non-melanomatous skin carcinoma or curatively treated carcinoma-in-situ of the cervix are excepted.

• Eastern Cooperative Oncology Group (ECOG) performance score of 3 or 4.

• Life expectancy less than 12 weeks.

• Complete bowel obstruction at the time of study enrolment.

• Receiving long-term anticoagulant therapy for an established indication (e.g., atrial fibrillation, mechanical heart valves).

• Bleeding diathesis (e.g., evidence of DIC, hereditary or acquired bleeding disorder).

• History of allergy to any heparin (e.g., heparin-induced thrombocytopenia).

• Significant cardiac history including myocardial infarction within preceding 6 months, congestive heart failure, clinically relevant atrial or ventricular arrhythmias, history of 2nd or 3rd degree heart blocks unless pacemaker is implanted.

• Serious medical conditions that preclude the administration of chemotherapy, anticoagulant therapy, or adherence to protocol, including but not exclusive to:

1. Allergic reactions to drugs containing cremophor or compounds chemically related to taxanes or platinum analogues.

2. Significant neurologic or psychiatric disorder that would impair obtaining informed consent and reliable follow-up.

3. Uncontrolled hypertension despite optimal medical therapy.

4. Active, uncontrolled infection.

• Women who are pregnant or lactating or are of childbearing potential but are not using effective contraception.

• Total body weight of less than 40 kg.

• Concurrent treatment with experimental or investigational drugs.

• Unable or unwilling to attend scheduled follow-ups.

• Unable (e.g., language barrier, mental illness) to provide informed consent.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Drug:
• dalteparin
50, 100, 150 IU/kg administered subcutaneously once daily for 3 cycles of chemotherapy

Locations

Country	Name	City	State
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Nova Scotia Cancer Centre	Halifax	Nova Scotia
Canada	Juravinski Cancer Centre	Hamilton	Ontario
Canada	London Health Sciences Centre	London	Ontario
Canada	Hopital Notre-Dame	Montreal	Quebec
Canada	The Ottawa Hospital Cancer Centre	Ottawa	Ontario
Canada	B.C. Cancer Agency- Fraser Valley Centre	Surrey	British Columbia
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	B.C. Cancer Agency- Vancouver Centre	Vancouver	British Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Ontario Clinical Oncology Group (OCOG)	Pfizer

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	disease response		up to day 1 of cycle 6	No
Secondary	symptomatic venous thromboembolism		up to 7 days after last dose of dalteparin	Yes
Secondary	bleeding		up to 24 hours after last dose of dalteparin	Yes
Secondary	compliance		up to the end of cycle 3	No
Secondary	death		up to the last day of follow-up	Yes