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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2013-01208 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| 08-015 | |||
| 08-04-097 | Other Identifier | Albert Einstein College of Medicine | |
| P30CA013330 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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This phase II trial studies how well pemetrexed disodium and carboplatin work in treating patients with recurrent ovarian, primary peritoneal, or fallopian tube cancer. Drugs used in chemotherapy, such as pemetrexed disodium and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.
PRIMARY OBJECTIVES:
I. To evaluate the response rate of combination pemetrexed (pemetrexed disodium) (Alimta) and carboplatin (Paraplatin) in recurrent ovarian, primary peritoneal, and fallopian tube carcinoma.
SECONDARY OBJECTIVES:
I. To evaluate the progression free interval, overall survival, and adverse effects among patients receiving this drug combination.
OUTLINE:
Patients receive pemetrexed disodium intravenously (IV) over 8-15 minutes and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for at least 6 courses in the absence of disease progression or unacceptable toxicity.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment (pemetrexed disodium, carboplatin) | Experimental | Patients receive pemetrexed disodium IV over 8-15 minutes and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for at least 6 courses in the absence of disease progression or unacceptable toxicity. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Carboplatin | Drug | Given IV |
|
| Measure | Description | Time Frame |
|---|---|---|
| Overall Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors and by Rustin's Criteria (RECIST) | The primary endpoint is overall response rate defined by proportion of patients achieving complete response, partial response based on RECIST V1.1 or Rustin's criteria as appropriate. Based on RECIST V1.1 for targeting lesions from CT scan: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions; Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; Overall response CR + PR. Based on Rustin's criteria, a response to ca125 has occurred if there is at least a 50% reduction in ca125 level from a pretreatment sample. The response must be confirmed and maintained for at least 28 days. | 4.5 years |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Toxicities | Secondary outcome included detailed measurement of adverse events from treatment assessed according to National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 3.0. | 4.5 years |
| Overall Survival (OS) |
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Inclusion Criteria:
Patients must have a histopathologically confirmed diagnosis of epithelial ovarian, primary peritoneal, or fallopian tube carcinoma
Patients must have received at least 1 prior platinum and taxane based chemotherapy regimen; patients may have failed no more than 2 prior chemotherapy regimens
Patients must have "platinum sensitive" disease, which will be defined as those patients with relapsed disease who had an initial complete remission, and relapsed more than 6 months after completion of initial platinum based chemotherapy
Recurrent disease must be confirmed by:
Bidimensionally measurable disease which can be measured by physical examination or by means of medical imaging techniques (measurable disease)
Two confirmed serum cancer antigen-125 (CA-125) levels greater than or equal to 70 u/ml (or 2 x upper limit of normal) separated by 1 week and obtained within 4 weeks prior to entry to the study (evaluable disease)
Patients must not have had other myelosuppressive therapy within four weeks of initiating pemetrexed/ carboplatin therapy
Patients must have recovered from effects of recent surgery
Patients must have a Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2
White blood cell (WBC) greater than or equal to 3,000/ul
Platelet count greater or equal to 100,000/ul
Neutrophil count greater or equal to 1,500/ul
Creatinine clearance >= 45 ml/min (estimated creatinine clearance by Cockcroft-Gault equation acceptable)
Total bilirubin =< to 1.5 mg/dL
Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) =< three times the upper normal institutional limits; if patient has known hepatic metastases, patients may be enrolled if liver function test is =< five times the upper normal institutional limits
Alkaline phosphatase =< three times the upper normal institutional limits; if patient has known hepatic metastases, patients may be enrolled if liver function test is =< five times the upper normal institutional limits
Patient must have signed informed consent
Patients must be willing to take the dexamethasone, folic acid and vitamin B12 supplementation as indicated in the protocol to reduce adverse drug toxicity
Patients must be willing to interrupt aspirin and other nonsteroidal anti-inflammatory drugs (NSAID) intake for 2 days before, day of, and 2 days after each chemotherapy treatment; low dose 80 mg aspirin and cyclooxygenase-2 (Cox-2) inhibitors are excluded from this restriction; if concomitant administration of an NSAID is necessary, patients should be monitored closely
Patients must have a life expectancy of greater than 12 weeks
Patients may not have concurrent or previous invasive malignancies, with the exception of non-melanoma skin cancer or no evidence of recurrence of previous malignancy within the last 5 years
Patients must have a current exam, blood work and any clinically indicated imaging studies within 4 weeks prior to study enrollment
Baseline folate and homocysteine blood levels
The ability to interrupt NSAIDS 2 days before (5 days for long-acting NSAIDs), the day of, and 2 days following administration of Alimta
The ability to take folic acid, vitamin B12, and dexamethasone according to protocol
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Dennis Kuo | Albert Einstein College of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Columbia University Medical Center | New York | New York | 10032 | United States | ||
| Memorial Sloan-Kettering Cancer Center |
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The sample size calculation was based on the primary endpoint of ORR. According to the Simon 2 stage design, the maximum trial size was set at 46 evaluable patients and stopping rules were based on the error probability limits of α=0.05 and β=0.1. If < 8 responses were observed among the initial 22 patients, the study would be terminated.
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| ID | Title | Description |
|---|---|---|
| FG000 | Treatment (Pemetrexed Disodium, Carboplatin) | Patients receive pemetrexed disodium IV over 8-15 minutes and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for at least 6 courses in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pemetrexed Disodium: Given IV |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Laboratory Biomarker Analysis | Other | Correlative studies |
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| Pemetrexed Disodium | Drug | Given IV |
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Kaplan-Meier method will be used t analyze the time-to-event data including overall survival (OS) and progression-free survival (PFS)
| First day of treatment on protocol to the date of death, or for living patients the last date of contact, assessed up to 4.5 years |
| Progression-free Interval | Kaplan-Meier curve will be used to examine all the time-to-event data points in analyzing progression free interval. | Time from the first day of treatment to the day that progression is first noted, assessed up to 4.5 years |
| New York |
| New York |
| 10065 |
| United States |
| Albert Einstein College of Medicine | The Bronx | New York | 10461 | United States |
| COMPLETED |
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| NOT COMPLETED |
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This is a open-labeled, phase II trial evaluating the combination of intravenous pemetrexed and carboplatin in patients with confirmed recurrent epithelial ovarian, primary peritoneal, or fallopian tube carcinoma. There is no comparison group.
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| ID | Title | Description |
|---|---|---|
| BG000 | Treatment (Pemetrexed Disodium, Carboplatin) | Patients receive pemetrexed disodium IV over 8-15 minutes and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for at least 6 courses in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pemetrexed Disodium: Given IV |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Site of Disease | Count of Participants | Participants |
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| FIGO Stage at Diagnosis | The stage reported here for the patients enrolled was the stage at their initial diagnosis. Surgical staging was performed primarily for the patients. Patients with Stage I disease had tumor spread that was confined to the pelvis. Patients with Stage II disease had tumor spread to organs/tissues surrounding the pelvis. Patients with Stage III had tumor spread to distant nodes or tissue within the pelvis. Patients with Stage IV disease had tumor spread to the upper abdomen, retroperitoneum, or other distant organs including lung and liver. | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Overall Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors and by Rustin's Criteria (RECIST) | The primary endpoint is overall response rate defined by proportion of patients achieving complete response, partial response based on RECIST V1.1 or Rustin's criteria as appropriate. Based on RECIST V1.1 for targeting lesions from CT scan: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions; Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; Overall response CR + PR. Based on Rustin's criteria, a response to ca125 has occurred if there is at least a 50% reduction in ca125 level from a pretreatment sample. The response must be confirmed and maintained for at least 28 days. | Intent to Treat Patients were included for primary endpoint analysis of ORR if they completed 3 cycles of therapy. Response was categorized as complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD) by RECIST criteria. All patients had | Posted | Count of Participants | Participants | 4.5 years |
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| Secondary | Incidence of Toxicities | Secondary outcome included detailed measurement of adverse events from treatment assessed according to National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 3.0. | The patients that received pemetrexed disodium with carboplatin treatment were evaluated for an grade, grade 3, and grade 4 toxicities for adverse event confirmations. | Posted | Number | Frequency of event | 4.5 years |
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| Secondary | Overall Survival (OS) | Kaplan-Meier method will be used t analyze the time-to-event data including overall survival (OS) and progression-free survival (PFS) | Posted | Median | 95% Confidence Interval | months | First day of treatment on protocol to the date of death, or for living patients the last date of contact, assessed up to 4.5 years |
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| Secondary | Progression-free Interval | Kaplan-Meier curve will be used to examine all the time-to-event data points in analyzing progression free interval. | Posted | Median | 95% Confidence Interval | months | Time from the first day of treatment to the day that progression is first noted, assessed up to 4.5 years |
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The median exposure to combination pemetrexed and carboplatin therapy was 18.9 weeks (range: 3-37.9 weeks). The safety population included all patients who received one cycle of chemotherapy and was included in the analysis of safety data.
Adverse events were graded on a scale of 1 to 4, for unfavorable medical occurrences in a participant whether or not considered related to the participant's participation in the research. The types of toxicities evaluated consisted of "hematologic" versus "non-hematologic." Treatment related deaths were recorded separately from all-cause mortality cases. Frequency of adverse events are calculated based on the total number of events divided by the total number of chemotherapy cycles given.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treatment (Pemetrexed Disodium, Carboplatin) | Patients receive pemetrexed disodium IV over 8-15 minutes and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for at least 6 courses in the absence of disease progression or unacceptable toxicity. Carboplatin: Given IV Laboratory Biomarker Analysis: Correlative studies Pemetrexed Disodium: Given IV | 0 | 22 | 11 | 22 | 0 | 22 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hematologic | Blood and lymphatic system disorders | Non-systematic Assessment | Neutropenia or Thrombocytopenia or Anemia |
| |
| Non-Hematologic | General disorders | Non-systematic Assessment | Elevated LFTs or Abdominal pain or Hypomagnesemia or Hyperglycemia or Hypersensitivity or Chest pain or Temporal parietal hemotoma or Bell's palsy |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Supervisor | Montefiore Medical Center | 718-405-8395 | bkhaksari@montefiore.org |
| ID | Term |
|---|---|
| D005185 | Fallopian Tube Neoplasms |
| D010051 | Ovarian Neoplasms |
| ID | Term |
|---|---|
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D005184 | Fallopian Tube Diseases |
| D000291 | Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |
| D004701 | Endocrine Gland Neoplasms |
| D010049 | Ovarian Diseases |
| D004700 | Endocrine System Diseases |
| D006058 | Gonadal Disorders |
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| ID | Term |
|---|---|
| D016190 | Carboplatin |
| D000068437 | Pemetrexed |
| ID | Term |
|---|---|
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D006147 | Guanine |
| D007042 | Hypoxanthines |
| D011688 | Purinones |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D005971 | Glutamates |
| D024342 | Amino Acids, Acidic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D000600 | Amino Acids, Dicarboxylic |
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| Hispanic |
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| Asian |
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| Fallopian Tube |
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| Title |
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| Measurements |
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| Progressive disease |
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