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

• Sponsor: Acrotech Biopharma LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01118624
• Collaborator: (none)
• Enrollment: 22
• Locations: 14
• Arm: 1
• Duration (Months): 28
• Patients Per Site: 1.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer; Breast Tumors; Neoplasms, Breast; Cancer of the Breast; Human Mammary Carcinoma	Drug: Pralatrexate Injection; Dietary Supplement: Vitamin B12; Dietary Supplement: Folic Acid	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 2 Study of Pralatrexate in Female Patients With Previously-treated Advanced or Metastatic Breast Cancer
• Study Start Date: Mar 1, 2010
• Actual Primary Completion Date: Apr 1, 2012
• Actual Study Completion Date: Jul 1, 2012

Arms and Interventions

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.

Drug: 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.; Other Names: FOLOTYN Pralatrexate PDX (RS)-10-propargyl-10-deazaaminopterin ; Dietary Supplement: Vitamin B12; 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 ; Dietary Supplement: Folic Acid; 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

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. 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.

3. 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).]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Providence Cancer Center	Portland	Oregon	United States	97213
2	The West Clinic	Memphis	Tennessee	United States	38120
3	Fakultní nemocnice Olomouc	Olomouc		Czechia	775 20
4	Multiscan, s.r.o.	Pardubice		Czechia	532 03
5	Fakultní nemocnice Královské Vinohrady - FNKV	Praha		Czechia	100 34
6	Centre Lutte Contre le Cancer Val d'Aurelle (CRLC)	Montpellier	Cedex 5	France	34298
7	Centre Régional de Lutte Contre le Cancer Alexis Vautrin	Vandœuvre-lès-Nancy	Meurthe-et-Moselle	France	54511
8	Centre Georges François Leclerc	Dijon Cedex		France	21079
9	Centre Léon Bérard	Lyon Cedex		France	69373
10	Institut Paoli Calmettes	Marseille		France	13273
11	Institut Jean-Godinot	Reims Cedex 09		France	51056
12	University of Debrecen Medical and Health Science Center	Debrecen	Hajdú-Bihar	Hungary	4032
13	Semmelweis University Budapest	Budapest		Hungary	H-1082
14	National Health Centre of Hungary	Budapest		Hungary	H-1145

Sponsors and Collaborators

• Acrotech Biopharma LLC

Investigators

• Study Director: Garry Weems, PharmD, Spectrum Pharmaceuticals, Inc

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Acrotech Biopharma LLC
• ClinicalTrials.gov Identifier: NCT01118624
• Other Study ID Numbers: PDX-014; 2008-006425-14
• First Posted: May 7, 2010
• Last Update Posted: Jan 7, 2020
• Last Verified: Jan 1, 2020

• Keywords provided by Acrotech Biopharma LLC: Female; Advanced; Metastatic
• Additional relevant MeSH terms: Breast Neoplasms; Vitamins; Folic Acid; Vitamin B 12; Hydroxocobalamin; Vitamin B Complex; 10-deazaaminopterin; Aminopterin

Study Results

Participant Flow

Recruitment Details	Patients were enrolled between 05 Oct 2009 and 10 May 2011. Patients were enrolled in Hungary, France, and the Czech Republic.

Arm/Group Title	Pralatrexate
Arm/Group Description	Study drug 190 mg/m^2 for 2 to 4 weeks.
Period Title: Overall Study
STARTED	22
COMPLETED	0
NOT COMPLETED	22

Baseline Characteristics

Arm/Group Title	Pralatrexate
Arm/Group Description	Study drug 190 mg/m^2 for 2 to 4 weeks.
Overall Participants	22
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.4 (11.8)
Sex: Female, Male (Count of Participants)
Female	22 100%
Male	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	21 95.5%
More than one race	0 0%
Unknown or Not Reported	1 4.5%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR)
Description	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.
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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pralatrexate
Arm/Group Description	Study drug 190 mg/m^2 for 2 to 4 weeks.
Measure Participants	22
Number [participants]	1 4.5%

2. Secondary Outcome

Title	Duration of Response (DOR)
Description	One patient has a PR as response and duration of response was provided for that patient.
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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pralatrexate
Arm/Group Description	Study drug 190 mg/m^2 for 2 to 4 weeks.
Measure Participants	1
Number [days]	112

3. Secondary Outcome

Title	Overall Survival (OS)
Description	Number of days from first dose of pralatrexate to death.
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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pralatrexate
Arm/Group Description	Study drug 190 mg/m^2 for 2 to 4 weeks.
Measure Participants	22
Median (95% Confidence Interval) [months]	11.3

4. Secondary Outcome

Title	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).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pralatrexate
Arm/Group Description	Study drug 190 mg/m^2 for 2 to 4 weeks.
Measure Participants	22
Number [participants]	21 95.5%

Adverse Events

Time Frame	All treated patients will be followed for safety through 35 (± 5) days after their last dose or until all treatment-related AEs have resolved or returned to baseline/Grade 1, whichever is longer
Arm/Group Title	Pralatrexate
Arm/Group Description	Study drug 190 mg/m^2 for 2 to 4 weeks.
All Cause Mortality
	Pralatrexate
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Pralatrexate
	Affected / at Risk (%)	# Events
Total	6/22 (27.3%)
Blood and lymphatic system disorders
THROMBOCYTOPENIA	2/22 (9.1%)	2
Gastrointestinal disorders
MUCOSAL INFLAMMATION	2/22 (9.1%)	2
Respiratory, thoracic and mediastinal disorders
PLEURAL EFFUSION	2/22 (9.1%)	2
Other (Not Including Serious) Adverse Events
	Pralatrexate
	Affected / at Risk (%)	# Events
Total	1/22 (4.5%)
Blood and lymphatic system disorders
ANAEMIA	1/22 (4.5%)	1
FEBRILE NEUTROPENIA	1/22 (4.5%)	1
General disorders
PYREXIA	1/22 (4.5%)	1
Respiratory, thoracic and mediastinal disorders
DYSPNOEA	1/22 (4.5%)	1

Limitations/Caveats

Sufficient patients were enrolled.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.