- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01118624
Study of Pralatrexate in Female Patients With Previously-treated Breast Cancer
Phase 2 Study of Pralatrexate in Female Patients With Previously-treated Advanced or Metastatic Breast Cancer
Study Overview
Status
Conditions
Intervention / Treatment
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
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Olomouc, Czechia, 775 20
- Fakultni nemocnice Olomouc
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Pardubice, Czechia, 532 03
- Multiscan, s.r.o.
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Praha, Czechia, 100 34
- Fakultní nemocnice Královské Vinohrady - FNKV
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Dijon Cedex, France, 21079
- Centre Georges François Leclerc
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Lyon Cedex, France, 69373
- Centre Leon Berard
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Marseille, France, 13273
- Institut Paoli Calmettes
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Reims Cedex 09, France, 51056
- Institut Jean-Godinot
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Cedex 5
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Montpellier, Cedex 5, France, 34298
- Centre Lutte Contre le Cancer Val d'Aurelle (CRLC)
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Meurthe-et-Moselle
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Vandœuvre-lès-Nancy, Meurthe-et-Moselle, France, 54511
- Centre Régional de Lutte Contre le Cancer Alexis Vautrin
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Budapest, Hungary, H-1082
- Semmelweis University Budapest
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Budapest, Hungary, H-1145
- National Health Centre of Hungary
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Hajdú-Bihar
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Debrecen, Hajdú-Bihar, Hungary, 4032
- University of Debrecen Medical and Health Science Center
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Oregon
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Portland, Oregon, United States, 97213
- Providence Cancer Center
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Tennessee
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Memphis, Tennessee, United States, 38120
- The West Clinic
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
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
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 |
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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:
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:
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:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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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.
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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.
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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.
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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.
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One patient has a PR as response and duration of response was provided for that patient.
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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.
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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.
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Number of days from first dose of pralatrexate to death.
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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.
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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).
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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).
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms
- Neoplasms by Site
- Breast Diseases
- Breast Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Micronutrients
- Hematinics
- Folic Acid Antagonists
- Vitamins
- Folic Acid
- Vitamin B 12
- Hydroxocobalamin
- Vitamin B Complex
- 10-deazaaminopterin
- Aminopterin
Other Study ID Numbers
- PDX-014
- 2008-006425-14 (EUDRACT_NUMBER)
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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