Fragmin in Ovarian Cancer: Utility on Survival (FOCUS)

NCT00239980 | Completed Phase 2 DMC

• 1 other identifier: NRA6300011-FOCUS-II
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 9

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.

Conditions

Ovarian Cancer

Keywords

antineoplastic agent; ovarian cancer; fragmin; dalteparin

Outcome Measures

Primary Outcomes (1)

• disease response

  up to day 1 of cycle 6

Secondary Outcomes (4)

• 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

Study Arms (3)

A

ACTIVE COMPARATOR

50 IU/kg

Drug: dalteparin

B

ACTIVE COMPARATOR

100 IU/kg

Drug: dalteparin

C

ACTIVE COMPARATOR

150 IU/kg

Drug: dalteparin

Interventions

dalteparin DRUG

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

Also known as: brand name is fragmin

A; B; C

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ontario Clinical Oncology Group (OCOG): lead
• Pfizer: collaborator

Study Sites (9)

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

B.C. Cancer Agency- Fraser Valley Centre

Surrey, British Columbia, V3V 1Z2, Canada

Location

B.C. Cancer Agency- Vancouver Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Nova Scotia Cancer Centre

Halifax, Nova Scotia, B3H 1V7, Canada

Location

Juravinski Cancer Centre

Hamilton, Ontario, L8V 5C2, Canada

Location

London Health Sciences Centre

London, Ontario, N6A 4G5, Canada

Location

The Ottawa Hospital Cancer Centre

Ottawa, Ontario, K1H 8L6, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Hopital Notre-Dame

Montreal, Quebec, H2L 4M1, Canada

Location

Related Publications (1)

• Rutjes AW, Porreca E, Candeloro M, Valeriani E, Di Nisio M. Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy. Cochrane Database Syst Rev. 2020 Dec 18;12(12):CD008500. doi: 10.1002/14651858.CD008500.pub5.

  PMID: 33337539 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

Dalteparin

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• Laurie Elit, MD

  Juravinski Cancer Centre

  STUDY CHAIR

• Agnes Lee, MD

  Hamilton Health Sciences Henderson Division

  STUDY CHAIR

• Mark Levine, MD

  McMaster University, Ontario Clinical Oncology Group

  PRINCIPAL INVESTIGATOR

• Jim Julian, MMath

  McMaster University, Dept. of Clinical Epidemiology & Biostatistics

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: October 13, 2005
• First Posted: October 17, 2005
• Study Start: October 1, 2005
• Primary Completion: January 1, 2010
• Study Completion: January 1, 2010
• Last Updated: February 3, 2010

Record last verified: 2010-02

Locations

CA (9)