Ovarian CancerPhase 1/2NCT01188876
Carboplatin/Pralatrexate in Recurrent Platinum-Sensitive Ovarian, Fallopian or Primary Peritoneal Cancer
A Phase 1/2 study testing carboplatin, pralatrexate and Folic Acid in people with Ovarian Cancer and Fallopian Tube Cancer, run by Massachusetts General Hospital at 2 sites in United States.
Trial summary
Pralatrexate is a type of antifolate drug which means is restrains the production of folic acid in the body. Folic acids are used by tumors to increase tumor cell growth and division. It is believed that reducing folic acid will hinder the rapid division of tumor cells, their growth and production. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Ovarian Cancer, Fallopian Tube Cancer, Peritoneal Cancer
- What is being tested?
- carboplatin, pralatrexate and Folic Acid
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 2 sitesUnited States
- Study dates
- Aug 2010to Jul 2017
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must be diagnosed with a platinum-sensitive recurrence of epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.
- The following histologic subtypes are eligible: papillary serous, endometrioid, mucinous, clear cell, adenocarcinomas, transitional, and mixtures of the above.
- Patients must have at least one measurable lesion according to RECIST criteria via CT or MRI scan. CT of the chest should be performed if any known disease is present in the chest. Pleural effusions, ascites, bone metastases, CA125 tumor markers, and lesions located in previously radiated areas are not considered measurable.
- Patients must have received a platinum-containing regimen at initial diagnosis.
- ECOG Performance Status of 0, 1 or 2
- Patients may have received up to 2 prior chemotherapy regimens in the recurrent cancer setting
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- 18 years of age or older
- Life expectancy of greater than 12 weeks
- Baseline laboratory values must meet what is outlined in the protocol
- Patients must receive vitamin B12 and folic acid prior to starting treatment
- Complete recovery from previous chemotherapy or biologic therapy
- During the Phase II of the study, patients with significant ascites and/or pleural effusions will undergo consideration of drainage of these areas prior to starting carboplatin and pralatrexate.
- Women of childbearing potential must have a negative pregnancy test within 7 days prior to initiating chemotherapy on trial and must agree to practice effective method of birth control during the study and for six months after their last treatment.
- Patients must have a normal QTc interval
Who cannot join
- Prior pelvic radiotherapy to greater than 25% of bone marrow
- Any uncontrolled medical problem that in the opinion of the investigator would preclude safe administration of the study drugs.
- Past history of bone marrow transplantation or stem cell support
- Patient with known history of CNS metastasis is ineligible unless the patient has had treatment with surgery or radiation therapy, is neurologically stable, and does not require oral or intravenous corticosteroids or anticonvulsants.
- A history of prior malignancy except for adequately treated carcinoma in situ of the uterine cervix, incidental stage I endometrial cancer, basal cell or squamous cell skin cancer, or breast cancer (invasive or ductal carcinoma in situ) for which the patient has been disease-free for at least three years.
- Routine prophylactic use of G-CSF or GM-CSF within two weeks prior to study entry.
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- Clinically significant cardiac disease
- Uncontrolled hypercalcemia or diabetes mellitus
- Any signs of intestinal obstruction that interfere with bowel function and/or nutrition
- Grade 2 or greater peripheral neuropathy
- Participation in an investigational study within three weeks prior to study entry.
- History of anaphylactic shock to prior platinum chemotherapy that would preclude safe administration of study carboplatin.
- History of psychiatric disability or other central nervous system disorder as judged by the principal investigator that would be considered significant and that would preclude informed consent, safe administration of study medications and affecting ability to comply with study procedures.
- Doses of ibuprofen in excess of 400mg QID.
- Interval cytoreductive surgery planned for while subject is on-study.
- Recurrence/progression within 6 months of receiving ay platinum regimen
- Patients with either pleural effusions or ascites are not eligible for Phase I of the study
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
About this study
Official title: Phase I/II Study of Carboplatin and Pralatrexate in Patients With Recurrent Platinum-Sensitive Ovarian, Fallopian or Primary Peritoneal Cancer
Pralatrexate is a type of antifolate drug which means is restrains the production of folic acid in the body. Folic acids are used by tumors to increase tumor cell growth and division. It is believed that reducing folic acid will hinder the rapid division of tumor cells, their growth and production. Carboplatin is an FDA approved chemotherapy drug for ovarian, fallopian tube and primary peritoneal cancer. Some antifolate drugs are used with other chemotherapy drugs to enhance cancer-fighting characteristics. It is believed that the study drug pralatrexate may improve the anti-tumor effect of carboplatin. In this research study we are looking for the highest dose of pralatrexate that can be given safely in combination with carboplatin.
Read the detailed description
- 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.
- Conditions
- Ovarian Cancer, Fallopian Tube Cancer, Peritoneal Cancer
- Being tested
- carboplatin, pralatrexate, Folic Acid, Vitamin B12 Injection
- Keywords
- carboplatin, recurrent, platinum sensitive, pralatrexate
- Medical subject headings
- Ovarian Neoplasms, Fallopian Tube Neoplasms, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
carboplatinDrug
Given intravenously on Day 1 of each 28-day cycle
pralatrexateDrug
Given intravenously on Day 1 and Day 15 of each 28-day cycle.
Folic AcidDrug
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.
Vitamin B12 InjectionDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Carboplatin/Pralatrexate | Experimental | Not described Receives: Drug: carboplatin; Drug: pralatrexate; Drug: Folic Acid; Drug: Vitamin B12 Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD)
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.
Measured: 1 year
Best Overall Response
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
Measured: 1 Year
Secondary outcomes (5)
Overall Survival
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.
Measured: 6, 12, 18, and 24 months
Progression Free Survival
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.
Measured: 3 months, 6 months
Treatment Related Adverse Events
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.
Measured: 1 Year
Maximum Concentration of Drug in Plasma (Cmax)
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.
Measured: Day 1 and Day 15
Area Under the Plasma Drug Concentration-Time Curve (AUC)
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).
Measured: Day 1 and Day 15
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2010 (estimated)
- Study startAug 2010
- Primary completionJul 2016
- Study completionJul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Ovarian CancerStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Dana-Farber Cancer Institute, Brigham and Women's Hospital, National Comprehensive Cancer Network
- Responsible party
- Principal investigator, Marcela G. del Carmen, MD, Massachusetts General Hospital
- Investigators
- Marcela G. del Carmen, MD, MPH, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01188876
- Sponsor's protocol ID
- 10-113
- Status last verified
- Dec 2017
- First submitted
- 24 Aug 2010
- Last updated
- 19 Jan 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of Carboplatin and Pralatrexate in Patients With Recurrent Platinum-Sensitive Ovarian, Fallopian or Primary Peritoneal Cancer
- ClinicalTrials.gov ID
- NCT01188876
- Acronym / sponsor ID
- 10-113
- Conditions
- Ovarian Cancer, Fallopian Tube Cancer, Peritoneal Cancer
- Keywords
- carboplatin, recurrent, platinum sensitive, pralatrexate
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Dana-Farber Cancer Institute, Brigham and Women's Hospital, National Comprehensive Cancer Network
- Study start
- Aug 2010
- Primary completion
- Jul 2016 (actual)
- Study completion
- Jul 2017 (actual)
- First posted
- 26 Aug 2010 (estimated)
- Results
- Posted 19 Jan 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Pralatrexate is a type of antifolate drug which means is restrains the production of folic acid in the body. Folic acids are used by tumors to increase tumor cell growth and division. It is believed that reducing folic acid will hinder the rapid division of tumor cells, their growth and production. Carboplatin is an FDA approved chemotherapy drug for ovarian, fallopian tube and primary peritoneal cancer. Some antifolate drugs are used with other chemotherapy drugs to enhance cancer-fighting characteristics. It is believed that the study drug pralatrexate may improve the anti-tumor effect of carboplatin. In this research study we are looking for the highest dose of pralatrexate that can be given safely in combination with carboplatin.
Detailed description
- 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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Carboplatin/Pralatrexate | Experimental | Drug: carboplatin, Drug: pralatrexate, Drug: Folic Acid, Drug: Vitamin B12 Injection |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Patients must be diagnosed with a platinum-sensitive recurrence of epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.
- The following histologic subtypes are eligible: papillary serous, endometrioid, mucinous, clear cell, adenocarcinomas, transitional, and mixtures of the above.
- Patients must have at least one measurable lesion according to RECIST criteria via CT or MRI scan. CT of the chest should be performed if any known disease is present in the chest. Pleural effusions, ascites, bone metastases, CA125 tumor markers, and lesions located in previously radiated areas are not considered measurable.
- Patients must have received a platinum-containing regimen at initial diagnosis.
- ECOG Performance Status of 0, 1 or 2
Key exclusion criteria (17 listed)
- Prior pelvic radiotherapy to greater than 25% of bone marrow
- Any uncontrolled medical problem that in the opinion of the investigator would preclude safe administration of the study drugs.
- Past history of bone marrow transplantation or stem cell support
- Patient with known history of CNS metastasis is ineligible unless the patient has had treatment with surgery or radiation therapy, is neurologically stable, and does not require oral or intravenous corticosteroids or anticonvulsants.
- A history of prior malignancy except for adequately treated carcinoma in situ of the uterine cervix, incidental stage I endometrial cancer, basal cell or squamous cell skin cancer, or breast cancer (invasive or ductal carcinoma in situ) for which the patient has been disease-free for at least three years.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| carboplatinGiven intravenously on Day 1 of each 28-day cycle | Drug | Carboplatin/Pralatrexate |
| pralatrexateGiven intravenously on Day 1 and Day 15 of each 28-day cycle. | Drug | Carboplatin/Pralatrexate |
| Folic AcidGiven 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 | Carboplatin/Pralatrexate |
| Vitamin B12 InjectionGiven 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. | Drug | Carboplatin/Pralatrexate |
Primary outcome
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
5 secondary outcomes
Overall Survival
Time frame: 6, 12, 18, and 24 months
Progression Free Survival
Time frame: 3 months, 6 months
Treatment Related Adverse Events
Time frame: 1 Year
Maximum Concentration of Drug in Plasma (Cmax)
Time frame: Day 1 and Day 15
Area Under the Plasma Drug Concentration-Time Curve (AUC)
Time frame: Day 1 and Day 15
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jan 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marcela G. del Carmen, MD, MPH principal investigator
Massachusetts General Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing carboplatin, pralatrexate and Folic Acid in people with Ovarian Cancer and Fallopian Tube Cancer, run by Massachusetts General Hospital at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Jan 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD) (time frame: 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jan 2018.