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

Phase 2

Completed

Conditions: Breast Cancer
Breast Tumors
Neoplasms, Breast
Cancer of the Breast
Human Mammary Carcinoma

Interventions: Drug: Pralatrexate Injection
Dietary Supplement: Vitamin B12
Dietary Supplement: Folic Acid

Registration Number: NCT01118624

Lead Sponsor: Acrotech Biopharma Inc.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 22

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Pralatrexate, (RS)-10-propargyl-10-deazaaminopterin (Folotyn)	Vitamin B12	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.
Pralatrexate, (RS)-10-propargyl-10-deazaaminopterin (Folotyn)	Folic Acid	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.
Pralatrexate, (RS)-10-propargyl-10-deazaaminopterin (Folotyn)	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.

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	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.

Secondary Outcome Measures

Name	Time	Method
Duration of Response (DOR)	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.
Overall Survival (OS)	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.
Incidence of Adverse Events (AEs) and Laboratory Abnormalities	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).

Trial Locations

Locations (14): Centre Régional de Lutte Contre le Cancer Alexis Vautrin
🇫🇷
Vandœuvre-lès-Nancy, Meurthe-et-Moselle, France
Centre Lutte Contre le Cancer Val d'Aurelle (CRLC)
🇫🇷
Montpellier, Cedex 5, France
Multiscan, s.r.o.
🇨🇿
Pardubice, Czechia
The West Clinic
🇺🇸
Memphis, Tennessee, United States
Fakultní nemocnice Olomouc
🇨🇿
Olomouc, Czechia
Fakultní nemocnice Královské Vinohrady - FNKV
🇨🇿
Praha, Czechia
National Health Centre of Hungary
🇭🇺
Budapest, Hungary
Institut Jean-Godinot
🇫🇷
Reims Cedex 09, France
Centre Georges François Leclerc
🇫🇷
Dijon Cedex, France
Centre Léon Bérard
🇫🇷
Lyon Cedex, France
Institut Paoli Calmettes
🇫🇷
Marseille, France
Semmelweis University Budapest
🇭🇺
Budapest, Hungary
University of Debrecen Medical and Health Science Center
🇭🇺
Debrecen, Hajdú-Bihar, Hungary
Providence Cancer Center
🇺🇸
Portland, Oregon, United States