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Carboplatin/Pralatrexate in Recurrent Platinum-Sensitive Ovarian, Fallopian or Primary Peritoneal Cancer

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ClinicalTrials.gov Identifier: NCT01188876
Recruitment Status : Completed
First Posted : August 26, 2010
Results First Posted : January 19, 2018
Last Update Posted : January 19, 2018
Sponsor:
Collaborators:
Dana-Farber Cancer Institute
Brigham and Women's Hospital
National Comprehensive Cancer Network
Information provided by (Responsible Party):
Marcela G. del Carmen, MD, Massachusetts General Hospital

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Ovarian Cancer
Fallopian Tube Cancer
Peritoneal Cancer
Interventions Drug: carboplatin
Drug: pralatrexate
Drug: Folic Acid
Drug: Vitamin B12 Injection
Enrollment 50
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Carboplatin/Pralatrexate
Hide Arm/Group Description

carboplatin: Given intravenously on Day 1 of each 28-day cycle

pralatrexate: Given intravenously on Day 1 and Day 15 of each 28-day cycle.

Period Title: Overall Study
Started 50
Completed 50
Not Completed 0
Arm/Group Title Carboplatin/Pralatrexate
Hide Arm/Group Description

carboplatin: Given intravenously on Day 1 of each 28-day cycle

pralatrexate: Given intravenously on Day 1 and Day 15 of each 28-day cycle.

Overall Number of Baseline Participants 50
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 50 participants
59
(39 to 72)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 50 participants
Female
50
 100.0%
Male
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 50 participants
Hispanic or Latino
0
   0.0%
Not Hispanic or Latino
49
  98.0%
Unknown or Not Reported
1
   2.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 50 participants
White
48
  96.0%
Black or African American
1
   2.0%
Other
1
   2.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 50 participants
50
 100.0%
ECOG Performance Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 50 participants
0
34
  68.0%
1
16
  32.0%
[1]
Measure Description:

Eastern Cooperative Oncology Group (ECOG) score

  • 0: Asymptomatic (Fully active, able to carry on all pre-disease activities without restriction)
  • 1: Symptomatic but completely ambulatory (Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature. For example, light housework, office work)
Primary Site  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 50 participants
Ovary
34
  68.0%
Fallopian Tube
6
  12.0%
Peritoneal
5
  10.0%
Other
5
  10.0%
Histology Subtype  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 50 participants
Serous
30
  60.0%
Endometrioid
6
  12.0%
Transitional Cell
1
   2.0%
Carcinosarcoma
3
   6.0%
Other
10
  20.0%
1.Primary Outcome
Title Maximum Tolerated Dose (MTD)
Hide Description The maximum tolerated dose of Pralatrexate in combination with Carboplatin in this patient population. The unit is given in milligrams per square meter of body surface area. MTD was determined using a standard 3 + 3 dose escalation cohort, where 3 participants were enrolled on the starting dose of 30 mg/m2 and if no dose limiting toxicities (DLT) were experienced after a full cycle, 3 additional participants were enrolled at the next highest dose level. Each increase in dose level escalated the dose of Pralatrexate by 15 mg/m2. If during any dose level, 1 patient out of 3 develops a DLT, then 3 additional patients will be added to that dose level. If 2 out of the 3 patients placed on any dose level experience a DLT, the preceding dose is considered MTD. If 1/6 has a DLT, the next higher dose level will commence accrual (unless at level +5 and then accrual to the Phase I portion will stop). If ≥ 2 of 6 patients have a DLT, then the preceding dose will be considered MTD.
Time Frame 1 year
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The participants that participated in the phase 1 dose escalation portion of the study
Arm/Group Title Carboplatin/Pralatrexate
Hide Arm/Group Description:

carboplatin: Given intravenously on Day 1 of each 28-day cycle

pralatrexate: Given intravenously on Day 1 and Day 15 of each 28-day cycle.

Overall Number of Participants Analyzed 30
Measure Type: Number
Unit of Measure: mg/m^2
105
2.Primary Outcome
Title Best Overall Response
Hide Description

Summary of the best overall responses to treatment as assessed by RECIST (Response Evaluation Criteria In Solid Tumors).

  • Complete Response (CR): Disappearance of all target lesions
  • Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD
  • Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started
  • Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions
Time Frame 1 Year
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Carboplatin/Pralatrexate
Hide Arm/Group Description:

carboplatin: Given intravenously on Day 1 of each 28-day cycle

pralatrexate: Given intravenously on Day 1 and Day 15 of each 28-day cycle.

Overall Number of Participants Analyzed 50
Measure Type: Count of Participants
Unit of Measure: Participants
Complete Response
0
   0.0%
Partial Response
19
  38.0%
Stable Disease
24
  48.0%
Progressive Disease
5
  10.0%
Unevaluable
2
   4.0%
3.Secondary Outcome
Title Overall Survival
Hide Description The number of participants still alive at the given time points. The duration of time is measured from the start of treatment until death due to any cause, participants are censored at the date of the last evaluation. The number participants surviving at 6, 12, 18, and 24 months is shown.
Time Frame 6, 12, 18, and 24 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Carboplatin/Pralatrexate
Hide Arm/Group Description:

carboplatin: Given intravenously on Day 1 of each 28-day cycle

pralatrexate: Given intravenously on Day 1 and Day 15 of each 28-day cycle.

Overall Number of Participants Analyzed 50
Measure Type: Count of Participants
Unit of Measure: Participants
6 Months
49
  98.0%
12 Months
49
  98.0%
18 Months
46
  92.0%
24 Months
33
  66.0%
4.Secondary Outcome
Title Progression Free Survival
Hide Description The number of participants alive and without disease progression at the given time-points. Time is measured from the start of treatment. Progression is defined as having at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Time Frame 3 months, 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Carboplatin/Pralatrexate
Hide Arm/Group Description:

carboplatin: Given intravenously on Day 1 of each 28-day cycle

pralatrexate: Given intravenously on Day 1 and Day 15 of each 28-day cycle.

Overall Number of Participants Analyzed 50
Measure Type: Count of Participants
Unit of Measure: Participants
3 Months
44
  88.0%
6 Months
40
  80.0%
5.Secondary Outcome
Title Treatment Related Adverse Events
Hide Description Summary of the treatment related adverse events experienced by participants as assessed by Common Terminology Criteria for Adverse Events (CTCAE 4). Adverse events were assessed from the start of treatment until 30 days after the last dose of study drug.
Time Frame 1 Year
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Carboplatin/Pralatrexate
Hide Arm/Group Description:

carboplatin: Given intravenously on Day 1 of each 28-day cycle

pralatrexate: Given intravenously on Day 1 and Day 15 of each 28-day cycle.

Overall Number of Participants Analyzed 50
Measure Type: Count of Participants
Unit of Measure: Participants
Constipation
2
   4.0%
Mucositis
13
  26.0%
Nausea
16
  32.0%
Vomiting
2
   4.0%
Diarrhea
1
   2.0%
Anemia
5
  10.0%
Thrombocytopenia
8
  16.0%
Neutropenia
6
  12.0%
Febrile neutropenia
2
   4.0%
Hypersensitivity reaction
17
  34.0%
Hypomagnesemia
3
   6.0%
Pruritis
1
   2.0%
Rash
3
   6.0%
Fatigue
15
  30.0%
6.Secondary Outcome
Title Maximum Concentration of Drug in Plasma (Cmax)
Hide Description The maximum concentration of Pralatrexate at day 1 and 15 among phase 1 participants dosed at 105 milligrams per square meter of body surface area (mg/m2). The concentration is given in micrograms per milliliter.
Time Frame Day 1 and Day 15
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants that required a dose reduction due to an adverse event were excluded from the day 15 evaluation
Arm/Group Title Carboplatin/Pralatrexate
Hide Arm/Group Description:

carboplatin: Given intravenously on Day 1 of each 28-day cycle

pralatrexate: Given intravenously on Day 1 and Day 15 of each 28-day cycle.

Overall Number of Participants Analyzed 17
Mean (95% Confidence Interval)
Unit of Measure: ug/ml
Day 1 Number Analyzed 17 participants
23.87
(15.25 to 32.49)
Day 15 Number Analyzed 9 participants
17.61
(11.43 to 24.09)
7.Secondary Outcome
Title Area Under the Plasma Drug Concentration-Time Curve (AUC)
Hide Description Area under the plasma drug concentration-time curve (AUC) for phase 1 participants that were dosed at 105 mg/m2. AUC represents the actual body exposure to drug after administration of a dose of the drug and is expressed in micrograms * hour per milliliter (ug*h/mL).
Time Frame Day 1 and Day 15
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants that required a dose reduction due to an adverse event were excluded from the day 15 evaluation
Arm/Group Title Carboplatin/Pralatrexate
Hide Arm/Group Description:

carboplatin: Given intravenously on Day 1 of each 28-day cycle

pralatrexate: Given intravenously on Day 1 and Day 15 of each 28-day cycle.

Overall Number of Participants Analyzed 17
Mean (95% Confidence Interval)
Unit of Measure: ug*h/mL
Day 1
9.89
(7.20 to 12.58)
Day 15
8.01
(6.19 to 9.83)
Time Frame Adverse events information was collected from the start of treatment until 30 days after the last dose of study medication was received (median duration of 7 months)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Carboplatin/Pralatrexate
Hide Arm/Group Description

carboplatin: Given intravenously on Day 1 of each 28-day cycle

pralatrexate: Given intravenously on Day 1 and Day 15 of each 28-day cycle.

All-Cause Mortality
Carboplatin/Pralatrexate
Affected / at Risk (%)
Total   0/50 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Carboplatin/Pralatrexate
Affected / at Risk (%) # Events
Total   4/50 (8.00%)    
Blood and lymphatic system disorders   
Febrile Neutropenia  1  2/50 (4.00%)  2
Thrombocytopenia  1  2/50 (4.00%)  2
Thromboembolytic event  1  1/50 (2.00%)  1
Gastrointestinal disorders   
Mucositis Oral  1  1/50 (2.00%)  1
Dyspepsia  1  1/50 (2.00%)  1
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Carboplatin/Pralatrexate
Affected / at Risk (%) # Events
Total   50/50 (100.00%)    
Blood and lymphatic system disorders   
Anemia  1  16/50 (32.00%)  29
Febrile neutropenia  1  5/50 (10.00%)  7
Ear and labyrinth disorders   
Tinnitus  1  3/50 (6.00%)  3
Eye disorders   
Watering eyes  1  6/50 (12.00%)  6
Gastrointestinal disorders   
Abdominal distension  1  3/50 (6.00%)  3
Abdominal pain  1  15/50 (30.00%)  19
Bloating  1  3/50 (6.00%)  3
Colonic obstruction  1  3/50 (6.00%)  3
Constipation  1  21/50 (42.00%)  32
Diarrhea  1  11/50 (22.00%)  15
Gastritis  1  3/50 (6.00%)  3
Gastroesophageal reflux disease  1  7/50 (14.00%)  7
Gastrointestinal disorders - Other, specify  1  3/50 (6.00%)  3
Mucositis oral  1  24/50 (48.00%)  53
Nausea  1  34/50 (68.00%)  61
Vomiting  1  13/50 (26.00%)  19
General disorders   
Fatigue  1  40/50 (80.00%)  63
Fever  1  5/50 (10.00%)  5
General disorders and administration site conditions - Other, specify  1  3/50 (6.00%)  3
Pain  1  4/50 (8.00%)  5
Immune system disorders   
Allergic reaction  1  14/50 (28.00%)  15
Anaphylaxis  1  3/50 (6.00%)  3
Infections and infestations   
Upper respiratory infection  1  4/50 (8.00%)  4
Urinary tract infection  1  6/50 (12.00%)  10
Injury, poisoning and procedural complications   
Bruising  1  3/50 (6.00%)  3
Investigations   
Alanine aminotransferase increased  1  3/50 (6.00%)  3
Alkaline phosphatase increased  1  3/50 (6.00%)  3
Creatinine increased  1  3/50 (6.00%)  4
Neutrophil count decreased  1  18/50 (36.00%)  25
Platelet count decreased  1  19/50 (38.00%)  36
White blood cell decreased  1  5/50 (10.00%)  8
Metabolism and nutrition disorders   
Anorexia  1  4/50 (8.00%)  5
Hyperglycemia  1  3/50 (6.00%)  7
Hypocalcemia  1  3/50 (6.00%)  3
Hypokalemia  1  5/50 (10.00%)  5
Hypomagnesemia  1  22/50 (44.00%)  35
Musculoskeletal and connective tissue disorders   
Arthralgia  1  3/50 (6.00%)  3
Back pain  1  7/50 (14.00%)  7
Bone pain  1  3/50 (6.00%)  4
Flank pain  1  3/50 (6.00%)  3
Musculoskeletal and connective tissue disorder - Other, specify  1  3/50 (6.00%)  4
Pain in extremity  1  5/50 (10.00%)  5
Nervous system disorders   
Headache  1  3/50 (6.00%)  4
Nervous system disorders - Other, specify  1  3/50 (6.00%)  4
Peripheral motor neuropathy  1  3/50 (6.00%)  4
Peripheral sensory neuropathy  1  12/50 (24.00%)  12
Psychiatric disorders   
Anxiety  1  9/50 (18.00%)  9
Depression  1  5/50 (10.00%)  5
Insomnia  1  3/50 (6.00%)  4
Reproductive system and breast disorders   
Pelvic pain  1  3/50 (6.00%)  3
Respiratory, thoracic and mediastinal disorders   
Cough  1  10/50 (20.00%)  13
Epistaxis  1  6/50 (12.00%)  7
Sore throat  1  6/50 (12.00%)  10
Skin and subcutaneous tissue disorders   
Alopecia  1  5/50 (10.00%)  5
Rash acneiform  1  4/50 (8.00%)  5
Vascular disorders   
Hypertension  1  5/50 (10.00%)  6
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Marcela del Carmen, MD, MPH
Organization: Massachusetts General Hospital
Phone: 617-724-4800
Responsible Party: Marcela G. del Carmen, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01188876     History of Changes
Other Study ID Numbers: 10-113
First Submitted: August 24, 2010
First Posted: August 26, 2010
Results First Submitted: November 22, 2017
Results First Posted: January 19, 2018
Last Update Posted: January 19, 2018