Study of Pralatrexate in Female Patients With Previously-treated Breast Cancer

NCT ID: NCT01118624

Last Updated: 2020-01-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-03-31
• Study Completion Date: 2012-07-31

Brief Summary

The purpose of this study is to determine the efficacy (ability to provide a beneficial treatment of the disease) of pralatrexate for the treatment of female patients with advanced or metastatic breast cancer who have failed prior chemotherapy. Patients will receive vitamin B12 and folic acid supplementation.

Detailed Description

This is an open label, multi-center, Phase 2 study of pralatrexate with vitamin B12 and folic acid supplementation in patients with advanced or metastatic breast cancer who have failed prior treatment(s).

The start of study treatment is defined as the initiation of pralatrexate administration.

Pralatrexate will be administered as an intravenous (IV) push over 3-5 minutes on days 1 and 15 (± 1 day at each time point) of a 4-week cycle (ie, every [q] 2 weeks). The initial dose of pralatrexate will be 190 mg/m2. Dose reduction to 150 mg/m2 with further reduction to 120 mg/m2 and 100 mg/m2 will be allowed for defined toxicity (see Section 7.3). If 100 mg/m2 is not tolerated, pralatrexate must be discontinued.

Patients will receive vitamin supplementation consisting of vitamin B12, 1 mg intramuscular (IM) q 8-10 weeks and folic acid 1-1.25 mg by mouth (PO) once a day (QD). Patients must have received 1 mg vitamin B12 within 10 weeks prior to the initiation of pralatrexate and have received 7 days of 1-1.25 mg folic acid PO QD prior to the initiation of pralatrexate.

Vitamin supplementation will continue throughout the study and for at least 30 days after the last administration of pralatrexate.

Conditions

Breast Cancer; Breast Tumors; Neoplasms, Breast; Cancer of the Breast; Human Mammary Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pralatrexate, (RS)-10-propargyl-10-deazaaminopterin (Folotyn)

Intravenous (IV) push administration over 3-5 minutes. Initial dose: 190 mg/m2 Dose reductions per protocol: 150 mg/m2, 120 mg/m2, and 100 mg/m2 allowed for defined toxicities.

Administered on days 1 and 15 of a 4-week cycle (every 2 weeks) until criteria for discontinuation per the protocol are met.

Group Type: EXPERIMENTAL

Pralatrexate Injection

Intervention Type: DRUG

Intravenous (IV) push administration over 3-5 minutes.

Initial dose: 190 mg/m2

Dose reductions per protocol: 150 mg/m2, 120 mg/m2, and 100 mg/m2 allowed for defined toxicities.

Administered on days 1 and 15 of a 4-week cycle (every 2 weeks) until criteria for discontinuation per the protocol are met.

Vitamin B12

Intervention Type: DIETARY_SUPPLEMENT

1 mg intramuscular injection

Administered within 10 weeks prior to first dose of pralatrexate, every 8-10 weeks throughout the study and for at least 30 days after the last dose of pralatrexate.

Folic Acid

Intervention Type: DIETARY_SUPPLEMENT

1.0-1.25 mg orally

Administered daily for at least 7 days prior to first dose of pralatrexate, throughout the study and for at least 30 days after the last dose of pralatrexate.

Interventions

Pralatrexate Injection

Intravenous (IV) push administration over 3-5 minutes.

Initial dose: 190 mg/m2

Dose reductions per protocol: 150 mg/m2, 120 mg/m2, and 100 mg/m2 allowed for defined toxicities.

Administered on days 1 and 15 of a 4-week cycle (every 2 weeks) until criteria for discontinuation per the protocol are met.

Intervention Type: DRUG

Vitamin B12

1 mg intramuscular injection

Administered within 10 weeks prior to first dose of pralatrexate, every 8-10 weeks throughout the study and for at least 30 days after the last dose of pralatrexate.

Intervention Type: DIETARY_SUPPLEMENT

Folic Acid

1.0-1.25 mg orally

Administered daily for at least 7 days prior to first dose of pralatrexate, throughout the study and for at least 30 days after the last dose of pralatrexate.

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

FOLOTYN; Pralatrexate; PDX; (RS)-10-propargyl-10-deazaaminopterin; Cyanocobalamin; Vitamin B9; Folate; Folacin

Eligibility Criteria

Inclusion Criteria

• HER-2 negative advanced or metastatic breast cancer
• Disease has become worse after at least 1 prior chemotherapy regimen for advanced or metastatic disease
• Advanced or metastatic disease resistant to both a taxane and an anthracycline-containing chemotherapy regimen, or resistant to taxanes and for whom further anthracycline therapy is not indicated
• Patients with controlled brain metastases must have finished receiving radiation therapy and if on corticosteroids, be on a stable or tapering dose of ≤ 10 mg/day of prednisone or equivalent for at least 28 days prior to study entry
• Measurable disease
• Female 18 years of age or older
• Performance status less than or equal to 2
• Life expectancy of more than 3 months
• Blood, liver and kidney laboratory test results that meet protocol requirements
• Patients must have a negative serum pregnancy test within 14 days before enrollment and agree to use medically acceptable and effective birth control from enrollment until at least 30 days after the last dose of pralatrexate. Patients who are postmenopausal for at least 1 year (more than 12 months since last menses) or are surgically sterilized do not require this test.
• Willing to attend visits for repeat dosing and follow up
• Give written informed consent

Exclusion Criteria

• Patients with only bone metastasis
• Patients with a single metastatic site without histological proof that the lesion is metastatic breast cancer
• Patients with inflammatory breast cancer
• Treatment with systemic chemotherapy, hormone therapy, radiation therapy, or other investigational therapy within 3 weeks (6 weeks for nitrosoureas, mitomycin C) prior to enrollment, except for the following:

• Bisphosphonates, if ongoing
• Prior treatment with methotrexate
• Prior treatment with anti-angiogenics within 6 months prior to enrollment
• Have received more than 2 prior chemotherapy regimens (more than 3 if one of the treatments was neoadjuvant or adjuvant chemotherapy)
• Have previously received pralatrexate
• Have received more than the allowed maximum total dose of anthracycline
• Prior radiation therapy on more than 30% of bone marrow reserve or prior bone marrow/stem cell transplantation
• Congestive heart failure Class III/IV
• Uncontrolled hypertension (high blood pressure)
• Active infection or any serious medical condition, which would impair the ability of the patient to receive protocol treatment
• Females who are pregnant or breastfeeding
• Major surgery within 14 days of enrollment
• Another active cancer in addition to advanced or metastatic breast cancer, except well treated in situ cervical cancer and basal cell skin cancer
• Dementia or other altered mental status that would prevent the patient from understanding and giving informed consent or limit her ability to follow the study requirements
• Patients who are human immunodeficiency virus (HIV)-positive and have a CD4 count of less than 100 mm3 or detectable viral load within past 3 months and is receiving anti-retroviral therapy
• Patients with hepatitis B virus (HBV) or hepatitis C virus (HCV) who have a detectable viral load or immunological evidence of chronic active disease or receiving/requiring antiviral therapy

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Acrotech Biopharma Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Garry Weems, PharmD

Role: STUDY_DIRECTOR

Spectrum Pharmaceuticals, Inc

Locations

Providence Cancer Center

Portland, Oregon, United States

The West Clinic

Memphis, Tennessee, United States

Fakultní nemocnice Olomouc

Olomouc, , Czechia

Multiscan, s.r.o.

Pardubice, , Czechia

Fakultní nemocnice Královské Vinohrady - FNKV

Prague, , Czechia

Centre Lutte Contre le Cancer Val d'Aurelle (CRLC)

Montpellier, Cedex 5, France

Centre Régional de Lutte Contre le Cancer Alexis Vautrin

Vandœuvre-lès-Nancy, Meurthe-et-Moselle, France

Centre Georges François Leclerc

Dijon, , France

Centre Léon Bérard

Lyon, , France

Institut Paoli Calmettes

Marseille, , France

Institut Jean-Godinot

Reims, , France

University of Debrecen Medical and Health Science Center

Debrecen, Hajdú-Bihar, Hungary

Semmelweis University Budapest

Budapest, , Hungary

National Health Centre of Hungary

Budapest, , Hungary

Countries

United States; Czechia; France; Hungary

Other Identifiers

2008-006425-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PDX-014

Identifier Type: -

Identifier Source: org_study_id