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

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Dennis Yi-Shin Kuo, Albert Einstein College of Medicine of Yeshiva University
ClinicalTrials.gov Identifier:
NCT01001910
First received: October 26, 2009
Last updated: December 10, 2015
Last verified: March 2015
  Purpose
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 Intervention Phase
Recurrent Fallopian Tube Carcinoma
Recurrent Ovarian Carcinoma
Recurrent Primary Peritoneal Carcinoma
Drug: Carboplatin
Other: Laboratory Biomarker Analysis
Drug: Pemetrexed Disodium
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Albert Einstein College of Medicine of Yeshiva University:

Primary Outcome Measures:
  • Overall objective response rate (RR) based on Response Evaluation Criteria in Solid Tumors and by Rustin Criteria (RECIST) [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]
    An exact 95% confidence interval for the tumor RR will be calculated based on the binomial distribution.


Secondary Outcome Measures:
  • Incidence of toxicities assessed according to National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 3.0. [ Time Frame: Up to 8 years ] [ Designated as safety issue: Yes ]
    Each of the grade 3 or 4 hematologic and non-hematologic toxicities will be determined and divided by the total number of patients to calculate the frequency for each toxicity over the study population. The number of adverse events will also be divided by the number of chemotherapy cycles to determine the frequency per treatment course.

  • Overall survival [ 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 8 years ] [ Designated as safety issue: No ]
    Kaplan-Meier method will be used to analyze the time-to-event data including overall survival.

  • Progression-free interval [ Time Frame: Time from the first day of treatment to the day that progression is first noted, assessed up to 8 years ] [ Designated as safety issue: No ]
    Kaplan-Meier method will be used to analyze the time-to-event data including progression free interval.


Enrollment: 12
Study Start Date: July 2008
Study Completion Date: February 2015
Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01001910

Locations
United States, New York
Albert Einstein College of Medicine
Bronx, New York, United States, 10461
Columbia University Medical Center
New York, New York, United States, 10032
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Albert Einstein College of Medicine of Yeshiva University
National Cancer Institute (NCI)
Investigators
Principal Investigator: Dennis Kuo Albert Einstein College of Medicine of Yeshiva University
  More Information

Responsible Party: Dennis Yi-Shin Kuo, Principal Investigator, Albert Einstein College of Medicine of Yeshiva University
ClinicalTrials.gov Identifier: NCT01001910     History of Changes
Other Study ID Numbers: 08-04-097  NCI-2013-01208  08-015  08-04-097  P30CA013330 
Study First Received: October 26, 2009
Last Updated: December 10, 2015
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Carcinoma
Ovarian Neoplasms
Fallopian Tube Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Fallopian Tube Diseases
Carboplatin
Pemetrexed
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on July 28, 2016