Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 31 of 35 for:    pralatrexate AND cells

Pralatrexate and Fluorouracil in Treating Patients With Recurrent Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01206465
Recruitment Status : Completed
First Posted : September 21, 2010
Results First Posted : July 16, 2018
Last Update Posted : July 16, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Jean Grem, MD, University of Nebraska

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Unspecified Adult Solid Tumor, Protocol Specific
Interventions Drug: pralatrexate
Drug: fluorouracil
Other: laboratory biomarker analysis
Genetic: DNA analysis
Other: high performance liquid chromatography
Genetic: polymerase chain reaction
Genetic: nucleic acid sequencing
Other: pharmacological study
Other: pharmacogenomic studies
Genetic: polymorphism analysis
Enrollment 29
Recruitment Details  
Pre-assignment Details 29 signed a consent form. Two patients never received any study drug: one became ineligible due to rise in bilirubin; another decided against participating.
Arm/Group Title 75 mg/m^2 94 mg/m^2 118 mg/m^2 148 mg/m^2 185 mg/m^2
Hide Arm/Group Description pralatrexate (PDX) dose level pralatrexate (PDX) dose level pralatrexate (PDX) dose level pralatrexate (PDX) dose level pralatrexate (PDX) dose level
Period Title: Overall Study
Started 3 6 6 6 6
Completed 3 6 6 6 6
Not Completed 0 0 0 0 0
Arm/Group Title Treatment (Enzyme Inhibitor Therapy)
Hide Arm/Group Description Patients receive pralatrexate IV over 5 minutes on day 1 and fluorouracil IV continuously over 48 hours on days 2 and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Baseline Participants 27
Hide Baseline Analysis Population Description
Analysis was performed on 27 patients who received study drug; 2 patients did not receive any study drug (1 changed mind after signing consent; 1 no longer eligible due to elevated bilirubin)
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 27 participants
61
(30 to 80)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 27 participants
Female
13
  48.1%
Male
14
  51.9%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Race/Ethnicity Number Analyzed 27 participants
Caucasian
24
  88.9%
Black, not of hispanic origin
1
   3.7%
Hispanic
1
   3.7%
Asian
1
   3.7%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 27 participants
27
1.Primary Outcome
Title Recommended Dose of PDX Given in Combination With a Fixed Dose of 5-FU Administered as a 48-hour Infusion Given Every Other Week
Hide Description Maximum tolerated dose will have been exceeded when 2 patients entered at a given dose level experience specified dose-limiting toxicities in the initial cycle
Time Frame During the initial course (day 1 & 15 of a 4 week schedule)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Enzyme Inhibitor Therapy)
Hide Arm/Group Description:
Patients receive pralatrexate IV over 5 minutes on day 1 and fluorouracil IV continuously over 48 hours on days 2 and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 27
Measure Type: Number
Unit of Measure: mg per meter square
148
2.Secondary Outcome
Title Number of Participants With Response to Therapy in Subjects With Measurable Disease
Hide Description [Not Specified]
Time Frame restaging imaging done after each two 4-week course until time of progression (the maximum duration of PFS = 588 days)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Enzyme Inhibitor Therapy)
Hide Arm/Group Description:
Patients receive pralatrexate IV over 5 minutes on day 1 and fluorouracil IV continuously over 48 hours on days 2 and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 27
Measure Type: Count of Participants
Unit of Measure: Participants
complete or partial response
0
   0.0%
stable disease
18
  66.7%
progressive disease
9
  33.3%
3.Secondary Outcome
Title Number of Patients Experiencing Grade 3-4 Toxicity While Receiving the Combination of PDX and 5-FU
Hide Description patients remained on study as long as they did not progress, and wished to continue on study (no limit on number of cycles)
Time Frame ., "From the time the subject signs the consent form and ending 4 weeks following the final chemotherapy, an average of 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Enzyme Inhibitor Therapy)
Hide Arm/Group Description:
Patients receive pralatrexate IV over 5 minutes on day 1 and fluorouracil IV continuously over 48 hours on days 2 and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 27
Measure Type: Number
Unit of Measure: participants
gr 3-4 neutropenia 4
gr 3-4 thrombocytopenia 0
gr 3-4 anemia 4
gr 3-4 diarrhea 1
gr 3-4 mucositis 5
gr 3-4 dehydration 1
gr 3-4 fatigue 1
4.Secondary Outcome
Title Pharmacokinetics of PDX- AUClast
Hide Description [Not Specified]
Time Frame Pre-treatment, end of infusion, at 15, 30, and 60 min, and then at 2, 4, 6, 8, 12, 22, 23, 24, 45, and 46 hours for PDX.
Hide Outcome Measure Data
Hide Analysis Population Description
AUClast
Arm/Group Title 75 mg/m^2 94 mg/m^2 118 mg/m^2 148 mg/m^2 185 mg/m^2
Hide Arm/Group Description:
pralatrexate (PDX) Dose level 1
PDX Dose Level 2
PDX Dose level 3
PDX Dose level 4
PDX Dose level 5
Overall Number of Participants Analyzed 3 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: ng/ml *hr
12,818  (578) 16300  (728) 15680  (801) 23570  (2411) 42121  (1051)
5.Secondary Outcome
Title Number of Participants With Polymorphisms in Methylenetetrahydrofolate Reductase and Thymidylate Synthase
Hide Description [Not Specified]
Time Frame Prior to the first dose of protocol therapy
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Wild Type Heterozygous Homozygous Variant
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 27 27 27
Measure Type: Number
Unit of Measure: percentage of patients
SLC19A1 80G>A 51.9 40.7 7.4
gamma glutamyl hydrolase (GGH) 401C>T 55.6 37.0 7.4
gamma glutamyl hydrolase (GGH) 452C>T 88.9 11.1 0
folyl polyglutamate synthase (FPGS) rs10760502A>G 96.0 4.0 0
folyl polyglutamate synthase (FPGS) rs1544105C>T 25.9 55.6 18.5
methylene tetrahydrofolate reductase (MTHFR 677C>T 55.6 25.9 18.5
methylene tetrahydrofolate reductase MTHFR 1298A>C 51.9 33.3 14.8
thymidylate synthase 28-bp tandem repeats (2 or 3) 14.8 48.2 37.0
6.Secondary Outcome
Title Pharmacokinetics of 5-FU - Cmax Plasma Levels
Hide Description 5-FU plasma levels
Time Frame 22, 23, 45 & 46 hours during the 48 hour infusion
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 22 Hours 23 Hours 45 Hours 46 Hours
Hide Arm/Group Description:
5 FU plasma levels
5 FU plasma levels
5 FU plasma levels
5 FU plasma levels
Overall Number of Participants Analyzed 27 27 27 27
Mean (Standard Deviation)
Unit of Measure: mg/m^2
1147  (133) 1159  (121) 1123  (130) 1113  (135)
7.Secondary Outcome
Title Time to Disease Progression in All Participants
Hide Description [Not Specified]
Time Frame restaging imaging done after each two 4-week course until time of progression (longest time to progression = 588 days)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Enzyme Inhibitor Therapy)
Hide Arm/Group Description:
Patients receive pralatrexate IV over 5 minutes on day 1 and fluorouracil IV continuously over 48 hours on days 2 and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 27
Median (Full Range)
Unit of Measure: days
112
(28 to 588)
Time Frame Adverse event data is collected on participants from the time of consent until 30 days after the participant is off study drug.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Treatment (Enzyme Inhibitor Therapy)
Hide Arm/Group Description Patients receive pralatrexate IV over 5 minutes on day 1 and fluorouracil IV continuously over 48 hours on days 2 and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
All-Cause Mortality
Treatment (Enzyme Inhibitor Therapy)
Affected / at Risk (%)
Total   3/27 (11.11%)    
Show Serious Adverse Events Hide Serious Adverse Events
Treatment (Enzyme Inhibitor Therapy)
Affected / at Risk (%) # Events
Total   10/27 (37.04%)    
Gastrointestinal disorders   
gastrointestinal disorders - Other  1 [1]  1/27 (3.70%)  1
Abdominal pain  1  3/27 (11.11%)  3
Diarrhea  1  2/27 (7.41%)  2
Nausea  1  1/27 (3.70%)  1
Vomiting  1  1/27 (3.70%)  1
General disorders   
Pain  1  2/27 (7.41%)  2
Infections and infestations   
Sepsis  1  1/27 (3.70%)  1
Infection and infestations- Other  1 [2]  1/27 (3.70%)  1
Joint infection  1 [3]  1/27 (3.70%)  1
Injury, poisoning and procedural complications   
Fracture  1 [4]  1/27 (3.70%)  1
Wound complication  1 [5]  1/27 (3.70%)  2
Metabolism and nutrition disorders   
Dehydration  1  1/27 (3.70%)  1
Nervous system disorders   
Nervous system disorders- Other  1 [6]  1/27 (3.70%)  1
Vascular disorders   
Thromboembolic Event  1 [7]  4/27 (14.81%)  4
hypotension  1  1/27 (3.70%)  1
1
Term from vocabulary, CTCAE (3.0)
Indicates events were collected by systematic assessment
[1]
diverticulitis
[2]
related to mucositis
[3]
knee
[4]
tibia bone
[5]
surgery
[6]
mental status change
[7]
Pulmonary emboli
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Treatment (Enzyme Inhibitor Therapy)
Affected / at Risk (%) # Events
Total   27/27 (100.00%)    
Blood and lymphatic system disorders   
Anemia  1  20/27 (74.07%)  20
Gastrointestinal disorders   
Mucositis oral  1  23/27 (85.19%)  23
Ascites  1  2/27 (7.41%)  2
Diarrhea  1  11/27 (40.74%)  11
Nausea  1  8/27 (29.63%)  8
constipation  1  2/27 (7.41%)  2
General disorders   
Localized Edema  1  2/27 (7.41%)  2
Fatigue  1  15/27 (55.56%)  15
Investigations   
white blood cell decreased  1  2/27 (7.41%)  3
Neutrophil count decreased  1  13/27 (48.15%)  13
Platelet count decreased  1  16/27 (59.26%)  16
Metabolism and nutrition disorders   
Hypoalbuminemia  1  2/27 (7.41%)  2
Hypokalemia  1  2/27 (7.41%)  2
dehydration  1  9/27 (33.33%)  9
Renal and urinary disorders   
Hemoglobinuria  1  5/27 (18.52%)  10
Skin and subcutaneous tissue disorders   
rash, maculo-papular  1  7/27 (25.93%)  7
1
Term from vocabulary, CTCAE (3.0)
Indicates events were collected by systematic assessment
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Jean L. Grem,MD
Organization: University of Nebraska Medical Center
Phone: 402-559-5166
EMail: jgrem@unmc.edu
Layout table for additonal information
Responsible Party: Jean Grem, MD, University of Nebraska
ClinicalTrials.gov Identifier: NCT01206465     History of Changes
Other Study ID Numbers: 238-10
NCI-2010-02014 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
First Submitted: September 17, 2010
First Posted: September 21, 2010
Results First Submitted: February 4, 2018
Results First Posted: July 16, 2018
Last Update Posted: July 16, 2018