Pemetrexed and Carboplatin in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

• Sponsor: Albert Einstein College of Medicine (Other)
• Overall Status: Completed
• CT.gov ID: NCT01001910
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 22
• Locations: 3
• Arm: 1
• Duration (Months): 79
• Patients Per Site: 7.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma	Drug: Carboplatin; Other: Laboratory Biomarker Analysis; Drug: Pemetrexed Disodium	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. 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:

1. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Combination Pemetrexed (Alimta) and Carboplatin (Paraplatin) in Platinum Sensitive Recurrent Ovarian, Primary Peritoneal, and Fallopian Tube Carcinoma
• Study Start Date: Jul 1, 2008
• Actual Primary Completion Date: Jan 1, 2015
• Actual Study Completion Date: Feb 1, 2015

Arms and Interventions

Arm

Intervention/Treatment

Experimental: 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.

Drug: Carboplatin; Given IV; Other Names: Blastocarb Carboplat Carboplatin Hexal Carboplatino Carbosin Carbosol Carbotec CBDCA Displata Ercar JM-8 Nealorin Novoplatinum Paraplat Paraplatin Paraplatin AQ Paraplatine Platinwas Ribocarbo ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Pemetrexed Disodium; Given IV; Other Names: Alimta LY231514 N-[4-[2-(2-Amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic Acid Disodium Salt

Outcome Measures

Primary Outcome Measures

1. Overall Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors and by Rustin's Criteria (RECIST) [4.5 years]

   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.

Secondary Outcome Measures

1. Incidence of Toxicities [4.5 years]

   Secondary outcome included detailed measurement of adverse events from treatment assessed according to National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 3.0.

2. Overall Survival (OS) [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]

   Kaplan-Meier method will be used t analyze the time-to-event data including overall survival (OS) and progression-free survival (PFS)

3. Progression-free Interval [Time from the first day of treatment to the day that progression is first noted, assessed up to 4.5 years]

   Kaplan-Meier curve will be used to examine all the time-to-event data points in analyzing progression free interval.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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)

• Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded); each lesion must be >= 2.0 cm when measured by conventional techniques, including palpation, x-ray, computed tomography (CT), and magnetic resonance imaging (MRI), or >= 1.0 cm when measured by spiral CT; all measurable lesions up to a maximum of 5 lesions per organ and 10 lesions in total representative of all involved organs should be identified as target lesions and will be recorded and measured at baseline; all baseline evaluations of disease status should be performed as close as possible to the start of treatment and never more than 4 weeks before the beginning of treatment

• Target lesions should be selected on the basis of their size (lesions with the longest dimension, LD) and their suitability for accurate repetitive measurements by one consistent method of assessment (either clinically or by imaging techniques); a sum of LD for all target lesions will be calculated and reported as the baseline sum LD; the baseline sum LD will be used as reference to further characterize the objective tumor response of the measurable dimension of the disease; all other lesions (or sites of disease) should be identified as non-target lesions and should also be recorded at baseline OR

• 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:

• Patients who have had more than two prior chemotherapeutic regimens

• Patients who have had prior treatment with pemetrexed

• Patients with a GOG performance status of 3 or 4

• Patients with >= grade 2 neuropathy

• Patients who have received external beam whole pelvic or whole abdominal radiation treatment (>= 4500 centigray [cGy]) which would limit vascular capacity and reduce adequate drug delivery

• Patients with evidence of recurrence from another malignancy within the previous five years

• Patients with a concomitant malignancy other than squamous cell skin cancer

• Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements

• Patients who have received an investigational drug within the last 30 days that has not received regulatory approval

• Presence of third space fluid which cannot be controlled by drainage; for patients who develop or have baseline clinically significant pleural or peritoneal effusions (on the basis of symptoms or clinical examination) before or during initiation of Alimta therapy, consideration should be given to draining the effusion prior to dosing; however, if, in the investigator's opinion, the effusion represents progression of disease, the patient should be discontinued from study therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Albert Einstein College of Medicine	Bronx	New York	United States	10461
2	Columbia University Medical Center	New York	New York	United States	10032
3	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065

Sponsors and Collaborators

• Albert Einstein College of Medicine
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Dennis Kuo, Albert Einstein College of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Dennis Yi-Shin Kuo, Principal Investigator, Albert Einstein College of Medicine
• ClinicalTrials.gov Identifier: NCT01001910
• Other Study ID Numbers: 08-04-097; NCI-2013-01208; 08-015; 08-04-097; P30CA013330
• First Posted: Oct 27, 2009
• Last Update Posted: Oct 20, 2021
• Last Verified: Oct 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Carcinoma; Fallopian Tube Neoplasms; Recurrence; Carboplatin; Pemetrexed

Study Results

Participant Flow

Recruitment Details	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.

Arm/Group Title	Treatment (Pemetrexed Disodium, Carboplatin)
Arm/Group Description	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
Period Title: Overall Study
STARTED	28
COMPLETED	22
NOT COMPLETED	6

Baseline Characteristics

Arm/Group Title	Treatment (Pemetrexed Disodium, Carboplatin)
Arm/Group Description	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
Overall Participants	28
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	64
Sex: Female, Male (Count of Participants)
Female	28 100%
Male	0 0%
Race/Ethnicity, Customized (Count of Participants)
White	21 75%
African American	1 3.6%
Hispanic	3 10.7%
Asian	3 10.7%
Site of Disease (Count of Participants)
Ovary	23 82.1%
Primary Peritoneal	4 14.3%
Fallopian Tube	1 3.6%
FIGO Stage at Diagnosis (Count of Participants)
I/II	3 10.7%
III/IV	25 89.3%

Outcome Measures

1. Primary Outcome

Title	Overall Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors and by Rustin's Criteria (RECIST)
Description	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.
Time Frame	4.5 years

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Treatment (Pemetrexed Disodium, Carboplatin)
Arm/Group Description	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
Measure Participants	22
Complete response	4 14.3%
Partial response	5 17.9%
Stable disease	9 32.1%
Progressive disease	4 14.3%

2. Secondary Outcome

Title	Incidence of Toxicities
Description	Secondary outcome included detailed measurement of adverse events from treatment assessed according to National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 3.0.
Time Frame	4.5 years

Outcome Measure Data

Analysis Population Description

The patients that received pemetrexed disodium with carboplatin treatment were evaluated for an grade, grade 3, and grade 4 toxicities for adverse event confirmations.

Arm/Group Title	Treatment (Pemetrexed Disodium, Carboplatin)
Arm/Group Description	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
Measure Participants	22
Hematologic AE Any Grade	240
Non-Hematologic AE Any Grade	60

3. Secondary Outcome

Title	Overall Survival (OS)
Description	Kaplan-Meier method will be used t analyze the time-to-event data including overall survival (OS) and progression-free survival (PFS)
Time Frame	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Pemetrexed Disodium, Carboplatin)
Arm/Group Description	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
Measure Participants	22
PFS	6.8
OS	50.3

4. Secondary Outcome

Title	Progression-free Interval
Description	Kaplan-Meier curve will be used to examine all the time-to-event data points in analyzing progression free interval.
Time Frame	Time from the first day of treatment to the day that progression is first noted, assessed up to 4.5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Pemetrexed Disodium, Carboplatin)
Arm/Group Description	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
Measure Participants	22
Median (95% Confidence Interval) [months]	6.8

Adverse Events

Time Frame	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 Event Reporting Description	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.
Arm/Group Title	Treatment (Pemetrexed Disodium, Carboplatin)
Arm/Group Description	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
All Cause Mortality
	Treatment (Pemetrexed Disodium, Carboplatin)
	Affected / at Risk (%)	# Events
Total	0/22 (0%)
Serious Adverse Events
	Treatment (Pemetrexed Disodium, Carboplatin)
	Affected / at Risk (%)	# Events
Total	11/22 (50%)
Blood and lymphatic system disorders
Hematologic	8/22 (36.4%)	71
General disorders
Non-Hematologic	3/22 (13.6%)	15
Other (Not Including Serious) Adverse Events
	Treatment (Pemetrexed Disodium, Carboplatin)
	Affected / at Risk (%)	# Events
Total	0/22 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.