Fragmin in Ovarian Cancer: Utility on Survival (FOCUS)

Sponsor

Ontario Clinical Oncology Group (OCOG) (Other)

Overall Status

Completed

CT.gov ID

NCT00239980

Collaborator

Pfizer (Industry)

Enrollment

Locations

Arms

Duration (Months)

8.6

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer	Drug: dalteparin	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

77 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Oct 1, 2005

Actual Primary Completion Date :

Jan 1, 2010

Actual Study Completion Date :

Jan 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: A 50 IU/kg	Drug: dalteparin 50, 100, 150 IU/kg administered subcutaneously once daily for 3 cycles of chemotherapy Other Names: brand name is fragmin
Active Comparator: B 100 IU/kg	Drug: dalteparin 50, 100, 150 IU/kg administered subcutaneously once daily for 3 cycles of chemotherapy Other Names: brand name is fragmin
Active Comparator: C 150 IU/kg	Drug: dalteparin 50, 100, 150 IU/kg administered subcutaneously once daily for 3 cycles of chemotherapy Other Names: brand name is fragmin

Arm

Intervention/Treatment

Active Comparator: A

50 IU/kg

Drug: dalteparin

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

Other Names:

brand name is fragmin

Active Comparator: B

100 IU/kg

Drug: dalteparin

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

Other Names:

brand name is fragmin

Active Comparator: C

150 IU/kg

Drug: dalteparin

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

Other Names:

brand name is fragmin

Outcome Measures

Primary Outcome Measures

disease response [up to day 1 of cycle 6]

Secondary Outcome Measures

symptomatic venous thromboembolism [up to 7 days after last dose of dalteparin]
bleeding [up to 24 hours after last dose of dalteparin]
compliance [up to the end of cycle 3]
death [up to the last day of follow-up]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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:

Patient has a pelvic mass, AND
Any evidence of disease larger than 1 cm in the upper abdomen (unless proven stage IV), AND
Normal mammography within 6 weeks of randomization, AND
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:

Absolute granulocyte count of at least 1.5 x 10 9/L (1500 per cubic millimetre).
Platelet count of at least 150 x 109/L (100,000 per cubic millimetre).
Serum creatinine no greater than 177 micromol/L (2.0 mg/dL).
Total bilirubin level no greater than 1.5 times the upper limit of normal at the local centre.
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:

Allergic reactions to drugs containing cremophor or compounds chemically related to taxanes or platinum analogues.
Significant neurologic or psychiatric disorder that would impair obtaining informed consent and reliable follow-up.
Uncontrolled hypertension despite optimal medical therapy.
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
2	B.C. Cancer Agency- Fraser Valley Centre	Surrey	British Columbia	Canada	V3V 1Z2
3	B.C. Cancer Agency- Vancouver Centre	Vancouver	British Columbia	Canada	V5Z 4E6
4	Nova Scotia Cancer Centre	Halifax	Nova Scotia	Canada	B3H 1V7
5	Juravinski Cancer Centre	Hamilton	Ontario	Canada	L8V 5C2
6	London Health Sciences Centre	London	Ontario	Canada	N6A 4G5
7	The Ottawa Hospital Cancer Centre	Ottawa	Ontario	Canada	K1H 8L6
8	Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
9	Hopital Notre-Dame	Montreal	Quebec	Canada	H2L 4M1

Sponsors and Collaborators

Ontario Clinical Oncology Group (OCOG)
Pfizer

Investigators

Study Chair: Laurie Elit, MD, Juravinski Cancer Centre
Study Chair: Agnes Lee, MD, Hamilton Health Sciences Henderson Division
Principal Investigator: Mark Levine, MD, McMaster University, Ontario Clinical Oncology Group
Principal Investigator: Jim Julian, MMath, McMaster University, Dept. of Clinical Epidemiology & Biostatistics