Clinical trial NCT01118624: Study of Pralatrexate in Female Patients With Previously-treated Breast Cancer
Official title: Phase 2 Study of Pralatrexate in Female Patients With Previously-treated Advanced or Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Breast Tumors
Neoplasms, Breast
Cancer of the Breast
Human Mammary Carcinoma
Keywords: Female
Advanced
Metastatic
Lead sponsor: Acrotech Biopharma Inc.
Sponsor class: INDUSTRY
First posted: 2010-05-07
Enrollment: 22
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: 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 outcomes:
measure: Duration of Response (DOR)
timeFrame: 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.
measure: Overall Survival (OS)
timeFrame: 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.
measure: Incidence of Adverse Events (AEs) and Laboratory Abnormalities
timeFrame: 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).
Other outcomes:
Locations:
city: Portland
country: United States
facility: Providence Cancer Center
state: Oregon
city: Memphis
country: United States
facility: The West Clinic
state: Tennessee
city: Olomouc
country: Czechia
facility: Fakultní nemocnice Olomouc
city: Pardubice
country: Czechia
facility: Multiscan, s.r.o.
city: Praha
country: Czechia
facility: Fakultní nemocnice Královské Vinohrady - FNKV
city: Montpellier
country: France
facility: Centre Lutte Contre le Cancer Val d'Aurelle (CRLC)
state: Cedex 5
city: Vandœuvre-lès-Nancy
country: France
facility: Centre Régional de Lutte Contre le Cancer Alexis Vautrin
state: Meurthe-et-Moselle
city: Dijon Cedex
country: France
facility: Centre Georges François Leclerc
city: Lyon Cedex
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Reims Cedex 09
country: France
facility: Institut Jean-Godinot
city: Debrecen
country: Hungary
facility: University of Debrecen Medical and Health Science Center
state: Hajdú-Bihar
city: Budapest
country: Hungary
facility: Semmelweis University Budapest
city: Budapest
country: Hungary
facility: National Health Centre of Hungary
Study officials:
affiliation: Spectrum Pharmaceuticals, Inc
name: Garry Weems, PharmD
role: STUDY_DIRECTOR
References: