Trial Outcomes & Findings for Carboplatin/Pralatrexate in Recurrent Platinum-Sensitive Ovarian, Fallopian or Primary Peritoneal Cancer (NCT NCT01188876)

Last Updated: 2018-01-19

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

50 participants

Primary outcome timeframe

1 year

Results posted on

2018-01-19

Participant Flow

Participant milestones

Participant milestones
Measure	Carboplatin/Pralatrexate 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 Study STARTED	50
Overall Study COMPLETED	50
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Carboplatin/Pralatrexate n=50 Participants 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.
Age, Continuous	59 years n=5 Participants
Sex: Female, Male Female	50 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	49 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Race/Ethnicity, Customized White	48 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants
Region of Enrollment United States	50 Participants n=5 Participants
ECOG Performance Status 0	34 Participants n=5 Participants
ECOG Performance Status 1	16 Participants n=5 Participants
Primary Site Ovary	34 Participants n=5 Participants
Primary Site Fallopian Tube	6 Participants n=5 Participants
Primary Site Peritoneal	5 Participants n=5 Participants
Primary Site Other	5 Participants n=5 Participants
Histology Subtype Serous	30 Participants n=5 Participants
Histology Subtype Endometrioid	6 Participants n=5 Participants
Histology Subtype Transitional Cell	1 Participants n=5 Participants
Histology Subtype Carcinosarcoma	3 Participants n=5 Participants
Histology Subtype Other	10 Participants n=5 Participants

PRIMARY outcome

Timeframe: 1 year

Population: The participants that participated in the phase 1 dose escalation portion of the study

Outcome measures

Outcome measures
Measure	Carboplatin/Pralatrexate n=30 Participants 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.
Maximum Tolerated Dose (MTD)	105 mg/m^2

PRIMARY outcome

Timeframe: 1 Year

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

Outcome measures

Outcome measures
Measure	Carboplatin/Pralatrexate n=50 Participants 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.
Best Overall Response Complete Response	0 Participants
Best Overall Response Partial Response	19 Participants
Best Overall Response Stable Disease	24 Participants
Best Overall Response Progressive Disease	5 Participants
Best Overall Response Unevaluable	2 Participants

SECONDARY outcome

Timeframe: 6, 12, 18, and 24 months

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.

Outcome measures

Outcome measures
Measure	Carboplatin/Pralatrexate n=50 Participants 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 Survival 6 Months	49 Participants
Overall Survival 12 Months	49 Participants
Overall Survival 18 Months	46 Participants
Overall Survival 24 Months	33 Participants

SECONDARY outcome

Timeframe: 3 months, 6 months

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.

Outcome measures

Outcome measures
Measure	Carboplatin/Pralatrexate n=50 Participants 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.
Progression Free Survival 3 Months	44 Participants
Progression Free Survival 6 Months	40 Participants

SECONDARY outcome

Timeframe: 1 Year

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.

Outcome measures

Outcome measures
Measure	Carboplatin/Pralatrexate n=50 Participants 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.
Treatment Related Adverse Events Constipation	2 Participants
Treatment Related Adverse Events Mucositis	13 Participants
Treatment Related Adverse Events Nausea	16 Participants
Treatment Related Adverse Events Vomiting	2 Participants
Treatment Related Adverse Events Diarrhea	1 Participants
Treatment Related Adverse Events Anemia	5 Participants
Treatment Related Adverse Events Thrombocytopenia	8 Participants
Treatment Related Adverse Events Neutropenia	6 Participants
Treatment Related Adverse Events Febrile neutropenia	2 Participants
Treatment Related Adverse Events Hypersensitivity reaction	17 Participants
Treatment Related Adverse Events Rash	3 Participants
Treatment Related Adverse Events Fatigue	15 Participants
Treatment Related Adverse Events Hypomagnesemia	3 Participants
Treatment Related Adverse Events Pruritis	1 Participants

SECONDARY outcome

Timeframe: Day 1 and Day 15

Population: Participants that required a dose reduction due to an adverse event were excluded from the day 15 evaluation

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.

Outcome measures

Outcome measures
Measure	Carboplatin/Pralatrexate n=17 Participants 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.
Maximum Concentration of Drug in Plasma (Cmax) Day 1	23.87 ug/ml Interval 15.25 to 32.49
Maximum Concentration of Drug in Plasma (Cmax) Day 15	17.61 ug/ml Interval 11.43 to 24.09

SECONDARY outcome

Timeframe: Day 1 and Day 15

Population: Participants that required a dose reduction due to an adverse event were excluded from the day 15 evaluation

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).

Outcome measures

Outcome measures
Measure	Carboplatin/Pralatrexate n=17 Participants 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.
Area Under the Plasma Drug Concentration-Time Curve (AUC) Day 1	9.89 ug*h/mL Interval 7.2 to 12.58
Area Under the Plasma Drug Concentration-Time Curve (AUC) Day 15	8.01 ug*h/mL Interval 6.19 to 9.83

Adverse Events

Carboplatin/Pralatrexate

Serious events: 4 serious events

Other events: 50 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Carboplatin/Pralatrexate n=50 participants at risk 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.
Blood and lymphatic system disorders Febrile Neutropenia	4.0% 2/50 • Number of events 2 • 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)
Blood and lymphatic system disorders Thrombocytopenia	4.0% 2/50 • Number of events 2 • 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)
Blood and lymphatic system disorders Thromboembolytic event	2.0% 1/50 • Number of events 1 • 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)
Gastrointestinal disorders Mucositis Oral	2.0% 1/50 • Number of events 1 • 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)
Gastrointestinal disorders Dyspepsia	2.0% 1/50 • Number of events 1 • 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)

Other adverse events

Other adverse events
Measure	Carboplatin/Pralatrexate n=50 participants at risk 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.
Investigations White blood cell decreased	10.0% 5/50 • Number of events 8 • 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)
Ear and labyrinth disorders Tinnitus	6.0% 3/50 • Number of events 3 • 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)
Infections and infestations Upper respiratory infection	8.0% 4/50 • Number of events 4 • 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)
Infections and infestations Urinary tract infection	12.0% 6/50 • Number of events 10 • 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)
Gastrointestinal disorders Abdominal distension	6.0% 3/50 • Number of events 3 • 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)
Gastrointestinal disorders Abdominal pain	30.0% 15/50 • Number of events 19 • 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)
Investigations Alanine aminotransferase increased	6.0% 3/50 • Number of events 3 • 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)
Investigations Alkaline phosphatase increased	6.0% 3/50 • Number of events 3 • 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)
Immune system disorders Allergic reaction	28.0% 14/50 • Number of events 15 • 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)
Skin and subcutaneous tissue disorders Alopecia	10.0% 5/50 • Number of events 5 • 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)
Immune system disorders Anaphylaxis	6.0% 3/50 • Number of events 3 • 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)
Blood and lymphatic system disorders Anemia	32.0% 16/50 • Number of events 29 • 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)
Metabolism and nutrition disorders Anorexia	8.0% 4/50 • Number of events 5 • 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)
Gastrointestinal disorders Vomiting	26.0% 13/50 • Number of events 19 • 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)
Psychiatric disorders Anxiety	18.0% 9/50 • Number of events 9 • 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)
Musculoskeletal and connective tissue disorders Arthralgia	6.0% 3/50 • Number of events 3 • 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)
Musculoskeletal and connective tissue disorders Back pain	14.0% 7/50 • Number of events 7 • 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)
Gastrointestinal disorders Bloating	6.0% 3/50 • Number of events 3 • 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)
Musculoskeletal and connective tissue disorders Bone pain	6.0% 3/50 • Number of events 4 • 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)
Injury, poisoning and procedural complications Bruising	6.0% 3/50 • Number of events 3 • 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)
Gastrointestinal disorders Colonic obstruction	6.0% 3/50 • Number of events 3 • 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)
Gastrointestinal disorders Constipation	42.0% 21/50 • Number of events 32 • 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)
Respiratory, thoracic and mediastinal disorders Cough	20.0% 10/50 • Number of events 13 • 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)
Investigations Creatinine increased	6.0% 3/50 • Number of events 4 • 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)
Psychiatric disorders Depression	10.0% 5/50 • Number of events 5 • 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)
Gastrointestinal disorders Diarrhea	22.0% 11/50 • Number of events 15 • 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)
Respiratory, thoracic and mediastinal disorders Epistaxis	12.0% 6/50 • Number of events 7 • 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)
General disorders Fatigue	80.0% 40/50 • Number of events 63 • 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)
Blood and lymphatic system disorders Febrile neutropenia	10.0% 5/50 • Number of events 7 • 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)
General disorders Fever	10.0% 5/50 • Number of events 5 • 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)
Musculoskeletal and connective tissue disorders Flank pain	6.0% 3/50 • Number of events 3 • 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)
Gastrointestinal disorders Gastritis	6.0% 3/50 • Number of events 3 • 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)
Gastrointestinal disorders Gastroesophageal reflux disease	14.0% 7/50 • Number of events 7 • 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)
Eye disorders Watering eyes	12.0% 6/50 • Number of events 6 • 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)
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	6.0% 3/50 • Number of events 3 • 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)
General disorders General disorders and administration site conditions - Other, specify	6.0% 3/50 • Number of events 3 • 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)
Nervous system disorders Headache	6.0% 3/50 • Number of events 4 • 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)
Metabolism and nutrition disorders Hyperglycemia	6.0% 3/50 • Number of events 7 • 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)
Vascular disorders Hypertension	10.0% 5/50 • Number of events 6 • 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)
Metabolism and nutrition disorders Hypocalcemia	6.0% 3/50 • Number of events 3 • 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)
Metabolism and nutrition disorders Hypokalemia	10.0% 5/50 • Number of events 5 • 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)
Metabolism and nutrition disorders Hypomagnesemia	44.0% 22/50 • Number of events 35 • 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)
Psychiatric disorders Insomnia	6.0% 3/50 • Number of events 4 • 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)
Gastrointestinal disorders Mucositis oral	48.0% 24/50 • Number of events 53 • 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)
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify	6.0% 3/50 • Number of events 4 • 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)
Gastrointestinal disorders Nausea	68.0% 34/50 • Number of events 61 • 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)
Nervous system disorders Nervous system disorders - Other, specify	6.0% 3/50 • Number of events 4 • 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)
Investigations Neutrophil count decreased	36.0% 18/50 • Number of events 25 • 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)
General disorders Pain	8.0% 4/50 • Number of events 5 • 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)
Musculoskeletal and connective tissue disorders Pain in extremity	10.0% 5/50 • Number of events 5 • 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)
Reproductive system and breast disorders Pelvic pain	6.0% 3/50 • Number of events 3 • 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)
Nervous system disorders Peripheral motor neuropathy	6.0% 3/50 • Number of events 4 • 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)
Nervous system disorders Peripheral sensory neuropathy	24.0% 12/50 • Number of events 12 • 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)
Investigations Platelet count decreased	38.0% 19/50 • Number of events 36 • 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)
Skin and subcutaneous tissue disorders Rash acneiform	8.0% 4/50 • Number of events 5 • 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)
Respiratory, thoracic and mediastinal disorders Sore throat	12.0% 6/50 • Number of events 10 • 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)

Additional Information

Marcela del Carmen, MD, MPH

Massachusetts General Hospital

Phone: 617-724-4800

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place