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

January 2, 2020 updated by: Acrotech Biopharma Inc.

Phase 2 Study of Pralatrexate in Female Patients With Previously-treated Advanced or Metastatic Breast Cancer

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.

Study Overview

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.

Study Type

Interventional

Enrollment (Actual)

22

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Olomouc, Czechia, 775 20
        • Fakultni nemocnice Olomouc
      • Pardubice, Czechia, 532 03
        • Multiscan, s.r.o.
      • Praha, Czechia, 100 34
        • Fakultní nemocnice Královské Vinohrady - FNKV
      • Dijon Cedex, France, 21079
        • Centre Georges François Leclerc
      • Lyon Cedex, France, 69373
        • Centre Leon Berard
      • Marseille, France, 13273
        • Institut Paoli Calmettes
      • Reims Cedex 09, France, 51056
        • Institut Jean-Godinot
    • Cedex 5
      • Montpellier, Cedex 5, France, 34298
        • Centre Lutte Contre le Cancer Val d'Aurelle (CRLC)
    • Meurthe-et-Moselle
      • Vandœuvre-lès-Nancy, Meurthe-et-Moselle, France, 54511
        • Centre Régional de Lutte Contre le Cancer Alexis Vautrin
      • Budapest, Hungary, H-1082
        • Semmelweis University Budapest
      • Budapest, Hungary, H-1145
        • National Health Centre of Hungary
    • Hajdú-Bihar
      • Debrecen, Hajdú-Bihar, Hungary, 4032
        • University of Debrecen Medical and Health Science Center
    • Oregon
      • Portland, Oregon, United States, 97213
        • Providence Cancer Center
    • Tennessee
      • Memphis, Tennessee, United States, 38120
        • The West Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: 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.

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
  • PDX
  • Pralatrexate
  • (RS)-10-propargyl-10-deazaaminopterin

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 Names:
  • Cyanocobalamin

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Tumor response evaluation was performed using RECIST 1.0 using CT/MRI. Proportion of patients achieving a CR or PR is considered in the overall response.
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.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
One patient has a PR as response and duration of response was provided for that patient.
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.
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.
Number of days from first dose of pralatrexate to death.
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.
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).
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).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2010

Primary Completion (ACTUAL)

April 1, 2012

Study Completion (ACTUAL)

July 1, 2012

Study Registration Dates

First Submitted

May 5, 2010

First Submitted That Met QC Criteria

May 5, 2010

First Posted (ESTIMATE)

May 7, 2010

Study Record Updates

Last Update Posted (ACTUAL)

January 7, 2020

Last Update Submitted That Met QC Criteria

January 2, 2020

Last Verified

January 1, 2020

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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