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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Spectrum Pharmaceuticals, Inc
ClinicalTrials.gov Identifier:
NCT01118624
First received: May 5, 2010
Last updated: May 8, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Breast Tumors
Neoplasms, Breast
Cancer of the Breast
Human Mammary Carcinoma
Drug: Pralatrexate Injection
Dietary Supplement: Vitamin B12
Dietary Supplement: Folic Acid
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 2 Study of Pralatrexate in Female Patients With Previously-treated Advanced or Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by Spectrum Pharmaceuticals, Inc:

Primary Outcome Measures:
  • Objective Response Rate (ORR) [ Time Frame: Assessed at the end of each even-numbered cycle (every 8 weeks), or per standard of care but no less than 4 weeks and nor more than every 12 weeks (+/- 1 week) if treatment has ended. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Duration of Response (DOR) [ Time Frame: Assessed at the end of each even-numbered cycle (every 8 weeks), or per standard of care but no less than 4 weeks and nor more than every 12 weeks (+/- 1 week) if treatment has ended. ] [ Designated as safety issue: No ]
  • Overall Survival (OS) [ Time Frame: Assessed at the end of each even-numbered cycle (every 8 weeks), or per standard of care but at least every 4 weeks and no more than every 12 weeks (+/- 1 week) if treatment has ended. OS will be collected for up to 2 years from start of pralatrexate. ] [ Designated as safety issue: No ]
  • Incidence of Adverse Events (AEs) and Laboratory Abnormalities [ Time Frame: Recorded at all study visits: every 2 weeks while on treatment and at safety follow-up (35 +/- 5 days post-last dose) or early termination visit (at time of withdrawal). ] [ Designated as safety issue: Yes ]
  • Evaluate Pharmacokinetic (PK) Parameters [ Time Frame: Sampling through 72 hours post end-injection of pralatrexate ] [ Designated as safety issue: Yes ]

Enrollment: 25
Study Start Date: March 2010
Study Completion Date: July 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: 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.

    Other Names:
    • FOLOTYN
    • Pralatrexate
    • PDX
    • (RS)-10-propargyl-10-deazaaminopterin
    Dietary Supplement: 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.

    Other Name: Cyanocobalamin
    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.

    Other Names:
    • Vitamin B9
    • Folate
    • Folacin
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01118624

Locations
United States, Oregon
Providence Cancer Center
Portland, Oregon, United States, 97213
United States, Tennessee
The West Clinic
Memphis, Tennessee, United States, 38120
Czech Republic
Fakultní nemocnice Olomouc
Olomouc, Czech Republic, 775 20
Multiscan, s.r.o.
Pardubice, Czech Republic, 532 03
Fakultní nemocnice Královské Vinohrady - FNKV
Praha, Czech Republic, 100 34
France
Centre Lutte Contre le Cancer Val d'Aurelle (CRLC)
Montpellier, Cedex 5, France, 34298
Centre Régional de Lutte Contre le Cancer Alexis Vautrin
Vandoeuvre, les Nancy Cedex, France, 54511
Centre Georges François Leclerc
Dijon Cedex, France, 21079
Centre Léon Bérard
Lyon Cedex, France, 69373
Institut Paoli Calmettes
Marseille, France, 13273
Institut Jean-Godinot
Reims Cedex 09, France, 51056
Hungary
University of Debrecen Medical and Health Science Center
Debrecen, Hajdú-Bihar, Hungary, 4032
National Health Centre of Hungary
Budapest, Hungary, H-1145
Semmelweis University Budapest
Budapest, Hungary, H-1082
Sponsors and Collaborators
Spectrum Pharmaceuticals, Inc
Investigators
Study Director: Garry Weems, PharmD Spectrum Pharmaceuticals, Inc
  More Information

No publications provided

Responsible Party: Spectrum Pharmaceuticals, Inc
ClinicalTrials.gov Identifier: NCT01118624     History of Changes
Other Study ID Numbers: PDX-014, 2008-006425-14
Study First Received: May 5, 2010
Last Updated: May 8, 2013
Health Authority: United States: Food and Drug Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Hungary: National Institute of Pharmacy

Keywords provided by Spectrum Pharmaceuticals, Inc:
Female
Advanced
Metastatic

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms
Carcinoma
Neoplasms by Site
Breast Diseases
Skin Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Folic Acid
Vitamin B Complex
Hydroxocobalamin
Vitamin B 12
Vitamins
10-deazaaminopterin
Aminopterin
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Hematinics
Hematologic Agents
Therapeutic Uses
Antineoplastic Agents
Folic Acid Antagonists
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 16, 2014