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

NCT01118624 | Completed Phase 2 Results

• 2 other identifiers: PDX-0142008-006425-14
• Study Type: interventional
• Target: 22
• Locations: 4 countries
• Sites: 14

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.

Conditions

Breast Cancer; Breast Tumors; Neoplasms, Breast; Cancer of the Breast; Human Mammary Carcinoma

Keywords

Female; Advanced; Metastatic

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  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 Outcomes (3)

• 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.

• 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.

• 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).

Study Arms (1)

Pralatrexate, (RS)-10-propargyl-10-deazaaminopterin (Folotyn)

EXPERIMENTAL

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.

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

Interventions

Pralatrexate Injection DRUG

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.

Also known as: FOLOTYN, Pralatrexate, PDX, (RS)-10-propargyl-10-deazaaminopterin

Pralatrexate, (RS)-10-propargyl-10-deazaaminopterin (Folotyn)

Vitamin B12 DIETARY_SUPPLEMENT

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.

Also known as: Cyanocobalamin

Pralatrexate, (RS)-10-propargyl-10-deazaaminopterin (Folotyn)

Folic Acid DIETARY_SUPPLEMENT

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.

Also known as: Vitamin B9, Folate, Folacin

Pralatrexate, (RS)-10-propargyl-10-deazaaminopterin (Folotyn)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Acrotech Biopharma Inc.: lead

Study Sites (14)

Providence Cancer Center

Portland, Oregon, 97213, United States

Location

The West Clinic

Memphis, Tennessee, 38120, United States

Location

Fakultní nemocnice Olomouc

Olomouc, 775 20, Czechia

Location

Multiscan, s.r.o.

Pardubice, 532 03, Czechia

Location

Fakultní nemocnice Královské Vinohrady - FNKV

Prague, 100 34, Czechia

Location

Centre Lutte Contre le Cancer Val d'Aurelle (CRLC)

Montpellier, Cedex 5, 34298, France

Location

Centre Régional de Lutte Contre le Cancer Alexis Vautrin

Vandœuvre-lès-Nancy, Meurthe-et-Moselle, 54511, France

Location

Centre Georges François Leclerc

Dijon, 21079, France

Location

Centre Léon Bérard

Lyon, 69373, France

Location

Institut Paoli Calmettes

Marseille, 13273, France

Location

Institut Jean-Godinot

Reims, 51056, France

Location

University of Debrecen Medical and Health Science Center

Debrecen, Hajdú-Bihar, 4032, Hungary

Location

Semmelweis University Budapest

Budapest, H-1082, Hungary

Location

National Health Centre of Hungary

Budapest, H-1145, Hungary

Location

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Interventions

10-propargyl-10-deazaaminopterin; Vitamin B 12; Folic Acid

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Corrinoids; Tetrapyrroles; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Macrocyclic Compounds; Polycyclic Compounds; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring

Limitations and Caveats

Sufficient patients were enrolled.

Results Point of Contact

• Title: Pankaj Sharma, MD
• Organization: Spectrum Pharmaceuticals

pankaj.sharma@sppirx.com

949-743-9264

Study Officials

• Garry Weems, PharmD

  Spectrum Pharmaceuticals, Inc

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2010
• First Posted: May 7, 2010
• Study Start: March 1, 2010
• Primary Completion: April 1, 2012
• Study Completion: July 1, 2012
• Last Updated: January 7, 2020
• Results First Posted: June 5, 2014

Record last verified: 2020-01

Locations

US (2); HU (3); CZ (3); FR (6)