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
|Condition or disease||Intervention/treatment||Phase|
|Ovarian Cancer Fallopian Tube Cancer Peritoneal Cancer||Drug: carboplatin Drug: pralatrexate Drug: Folic Acid Drug: Vitamin B12 Injection||Phase 1 Phase 2|
- Since we are looking for the highest dose of the study drug that can be administered safely without severe or unmanageable side effects, not everyone who participates will receive the same dose of the study drug.
- Each study cycle will last 28 days. On Day 1, participants will receive carboplatin intravenously. On Days 1 and 15 of each cycle they will receive pralatrexate intravenously. Participants will also be asked to take folic acid orally on a daily basis starting 7 days before the first dose of pralatrexate and continuing until 30 days after the last dose of pralatrexate. They will also receive a vitamin B12 injection no more than 10 weeks prior to the first dose of pralatrexate and every 8-10 weeks after the first dose of pralatrexate.
- Participants will come to the clinic on Day 1 and 15 of each cycle and have the following tests/procedures performed: Medical history; Vital signs; Blood tests, assessment of the tumor (every two cycles) and an EKG (before the start of cycle 2).
- In addition, during Cycle 1, participants will come to the clinic weekly for blood tests.
- Pharmacokinetic (PK) blood samples (to monitor how the body absorbs and breaks down the study drug) will be done at the following time points during Cycle 1: Day 1-3 and Day 15-17.
- Participants will be asked to take the study drugs for up to 6 cycles. They may continue beyond 6 cycles as long as there is evidence that the tumor is not growing and they are not experiencing any unacceptable side effects.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||50 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I/II Study of Carboplatin and Pralatrexate in Patients With Recurrent Platinum-Sensitive Ovarian, Fallopian or Primary Peritoneal Cancer|
|Study Start Date :||August 2010|
|Actual Primary Completion Date :||July 2016|
|Actual Study Completion Date :||July 2017|
Given intravenously on Day 1 of each 28-day cycle
Given intravenously on Day 1 and Day 15 of each 28-day cycle.
Drug: Folic Acid
Given orally on a daily basis starting 7 days before the first dose of pralatrexate and continuing until 30 days after the last dose of pralatrexate.
Drug: Vitamin B12 Injection
Given vitamin B12 injection no more than 10 weeks prior to the first dose of pralatrexate and every 8-10 weeks after the first dose of pralatrexate.
- Maximum Tolerated Dose (MTD) [ Time Frame: 1 year ]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.
- Best Overall Response [ Time Frame: 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
- Overall Survival [ Time Frame: 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.
- Progression Free Survival [ Time Frame: 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.
- Treatment Related Adverse Events [ Time Frame: 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.
- Maximum Concentration of Drug in Plasma (Cmax) [ Time Frame: Day 1 and Day 15 ]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.
- Area Under the Plasma Drug Concentration-Time Curve (AUC) [ Time Frame: Day 1 and Day 15 ]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).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01188876
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|Principal Investigator:||Marcela G. del Carmen, MD, MPH||Massachusetts General Hospital|