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Pemetrexed Disodium and Cisplatin in Treating Patients Undergoing Surgery For Stage I-III Non-Small Cell Lung Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Eli Lilly and Company
Information provided by (Responsible Party):
Roswell Park Cancer Institute
ClinicalTrials.gov Identifier:
NCT01731626
First received: September 12, 2012
Last updated: January 10, 2014
Last verified: January 2014
  Purpose

This phase II trial studies how well giving pemetrexed disodium and cisplatin works in treating patients who are undergoing surgery for stage I-III non-small cell lung cancer. Pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving these treatments before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving these treatments after surgery may kill any tumor cells that remain after surgery.


Condition Intervention Phase
Stage IB Non-small Cell Lung Cancer
Stage IIA Non-small Cell Lung Cancer
Stage IIB Non-small Cell Lung Cancer
Stage IIIA Non-small Cell Lung Cancer
Stage IIIB Non-small Cell Lung Cancer
Drug: cisplatin
Drug: pemetrexed disodium
Other: laboratory biomarker analysis
Procedure: positron emission tomography
Radiation: fludeoxyglucose F 18
Procedure: therapeutic conventional surgery
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Molecular and Genetic Changes in Patients With Resectable Non-Small Cell Lung Cancer (NSCLC) Following Neoadjuvant Chemotherapy With Cisplatin and Alimta - Phase II Study

Resource links provided by NLM:


Further study details as provided by Roswell Park Cancer Institute:

Primary Outcome Measures:
  • Pathologic complete response [ Time Frame: Up to day 63 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The frequency and severity of all adverse effects will be tabulated and reported using the Common Toxicity Criteria (CTC) version 3.0 [ Time Frame: Up to day 171 ] [ Designated as safety issue: Yes ]
    Serious adverse events will be monitored to determine the safety of the combination.

  • Overall survival [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
    Estimates will be computed using the Kaplan-Meier method.

  • Disease-free survival [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
    Estimates will be computed using the Kaplan-Meier method.


Estimated Enrollment: 52
Study Start Date: June 2005
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (chemotherapy and surgery)

NEOADJUVANT CHEMOTHERAPY: Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over approximately 1 hour on days 1, 22, and 43. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.

SURGERY: Patients undergo surgery between days 70-90.

ADJUVANT CHEMOTHERAPY: Beginning on day 130, patients receive pemetrexed disodium and cisplatin as in neoadjuvant chemotherapy. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.

Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Drug: pemetrexed disodium
Given IV
Other Names:
  • ALIMTA
  • LY231514
  • MTA
Other: laboratory biomarker analysis
Correlative studies
Procedure: positron emission tomography
Correlative studies
Other Names:
  • FDG-PET
  • PET
  • PET scan
  • tomography, emission computed
Radiation: fludeoxyglucose F 18
Correlative studies
Other Names:
  • 18FDG
  • FDG
Procedure: therapeutic conventional surgery
Undergo surgery

Detailed Description:

PRIMARY OBJECTIVES:

I. The primary goal is to determine whether or not these two agents given prior to surgery increase the chance that the surgical specimen will be pathologically negative (pathological complete response).

SECONDARY OBJECTIVES:

I. Document adverse events using this regimen in this setting. II. To document the overall and disease free survival. III. To correlate response with markers such as presence or absence of excision nuclease within the nucleotide excision repair 1 (ERCC1) and dihydrofolate reductase (DHFR), thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and glycinamide ribonucleotide formyl transferase (GARFT).

IV. Correlate pre- and post chemotherapy effects on fludeoxyglucose F18 (FDG) uptake by the tumor on positron emission tomography (PET) scan.

OUTLINE:

NEOADJUVANT CHEMOTHERAPY: Patients receive pemetrexed disodium intravenously (IV) over 10 minutes and cisplatin IV over approximately 1 hour on days 1, 22, and 43. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.

SURGERY: Patients undergo surgery between days 70-90.

ADJUVANT CHEMOTHERAPY: Beginning on day 130, patients receive pemetrexed disodium and cisplatin as in neoadjuvant chemotherapy. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then yearly thereafter.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Microscopically confirmed non-small cell carcinoma of the lung
  • No prior therapy for lung cancer
  • Patients must have disease stages IB (T2N0M0), IIA (T1N1M0), IIB (T2N1M0 and T3N0M0), or lIlA (T3N1M0 and T1-3N2M0); patients with satellite lesions in one lobe (T4) (stage IIIB) will also be eligible
  • Patients must be deemed surgically resectable by a thoracic surgeon
  • Patients must have either measurable or evaluable disease; measurable disease: any lesion that can be accurately measured in at least one dimension, with the longest diameter being >= 10 mm; evaluable disease: lesions apparent on computed tomography (CT), which do not meet the criteria for measurability; these include ill-defined masses associated with post obstructive changes and mediastinal or hilar adenopathy
  • Informed consent must be obtained
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Patients must be > 12 weeks from prior major surgery of the chest and abdomen
  • Calculated creatinine clearance (CrC1) >= 45 mL/min based on the Cockcroft and Gault formula
  • The ability to take folic acid, Vitamin B12, and dexamethasone according to protocol

Exclusion Criteria:

  • White bloods cell count < 3000/mm^3
  • Platelet count < 100,000/mm^3
  • Hemoglobin < 9 g/dl
  • Calculated creatinine clearance (CrCl) < 45 mL/min based on the Cockcroft and Gault formula
  • Total bilirubin > 1.5 mg/dl
  • Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvate transaminase (SGPT) > 1.5 x upper limit of normal
  • Metastatic disease (except peribronchial/hilar lymph nodes = N1 and ipsilateral/subcarinal mediastinal lymph nodes = N2) or malignant pleural effusion detected on preoperative evaluation; non-malignant effusions have negative cytology, are non-bloody, and are transudates; effusions visible only on CT and not large enough for safe thoracentesis will not result in ineligibility; exudative effusions, even if cytologically negative are excluded; pleural fluid is considered exudative if: the ratio of pleural fluid protein to serum protein is greater than 0.5, the ratio of pleural fluid lactate dehydrogenase (LDH) to serum to serum LDH > 0.6, pleural fluid LDH is greater than 200 RI/liter
  • N3 lymph nodes (contralateral mediastinal/hilar and supraclavicular/scalene) or T4 primary tumor (malignant pleural effusion or mediastinal invasion) by clinical staging criteria, (N3 as seen on CT or PET scan; patients may be eligible only if N3 nodes proven negative by mediastinoscopy and/or excisional biopsy of supraclavicular lymph node)
  • Presence of third space fluid which cannot be controlled by drainage; for patients who develop or have baseline clinically significant pleural or peritoneal effusions before or during initiation of pemetrexed 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 then the patient should be discontinued from study therapy
  • Prior chemotherapy, surgery, or radiation therapy for lung cancer
  • Pregnant or lactating
  • Other active malignancy within 2 years with the exceptions of nonmelanoma skin cancer and cervical carcinoma in situ
  • Psychological, familial, sociologic or geographic conditions, which do not permit medical follow-up and compliance with the study protocol
  • Inability to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAID) 2 days before, the day of and 2 days after the dose of Alimta (Pemetrexed); if a patient is taking a NSAID or a salicylate with a long half-life (for example, naproxen, piroxicam, diflunisal, nabumetone, rofecoxib, or celecoxib) it should not be taken 5 days before the dose of Alimta (Pemetrexed); (8 day period for long acting agents such as piroxicam), the day of, and 2 days after the dose of Alimta (Pemetrexed)
  • Squamous cell carcinoma histology
  • The screening PET scan will be used to exclude patients; if there are multiple areas of FDG uptake, outside the area of the primary tumor in the lung, or evidence of malignant pleural disease as evidenced by pleural nodules, the patient will be excluded by virtue of having metastatic disease; if however, only one area shows an increase in FDG uptake, the area of concern will need further evaluation such as a biopsy to exclude metastatic disease
  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: NCT01731626

Locations
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Rochester General Hospital
Rochester, New York, United States, 14621
Sponsors and Collaborators
Roswell Park Cancer Institute
Eli Lilly and Company
Investigators
Principal Investigator: Grace Dy Roswell Park Cancer Institute
  More Information

No publications provided

Responsible Party: Roswell Park Cancer Institute
ClinicalTrials.gov Identifier: NCT01731626     History of Changes
Other Study ID Numbers: I 31104, NCI-2010-02214
Study First Received: September 12, 2012
Last Updated: January 10, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Cisplatin
Fluorodeoxyglucose F18
Pemetrexed
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Diagnostic Uses of Chemicals
Enzyme Inhibitors
Folic Acid Antagonists
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Radiation-Sensitizing Agents
Radiopharmaceuticals
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014