NCTN: Randomized Phase III Study of Maintenance Therapy With Bevacizumab, Pemetrexed, or a Combination of Bevacizumab and Pemetrexed Following Carboplatin, Paclitaxel and Bevacizumab for Advanced Non-Squamous NSCLC (E5508)

Study ID: E5508

NCT Number: NCT01107626

ECOG-ACRIN Cancer Research Group

Submitted in collaboration with the NCTN/NCORP Data Archive

Trial Title: NCTN: Randomized Phase III Study of Maintenance Therapy with Bevacizumab, Pemetrexed, or a Combination of Bevacizumab and Pemetrexed following Carboplatin, Paclitaxel and Bevacizumab for Advanced Non-Squamous NSCLC (E5508)

Trial Description:

RATIONALE: Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of non-small cell lung cancer by blocking blood flow to the tumor. Pemetrexed disodium may stop the growth of tumor cells by blocking some enzymes needed for cell growth. It is not yet known whether giving bevacizumab or pemetrexed disodium alone or in combination is more effective in treating non-squamous non-small cell lung cancer.

PURPOSE: This randomized phase III trial is studying bevacizumab and pemetrexed disodium alone or in combination after induction therapy to see how well they work in treating patients with advanced non-squamous non-small cell lung cancer.

Clinical data presented in the following publication(s):

• PMID 31361535

Disease type(s): Lung, Mediastinal and Pleural Neoplasm - Non-Small Cell Lung Cancer

Clinical dataset(s) included:

• NCT01107626-D1 (PMID 31361535): There are two different datasets for PMID 31361535 from trial E5508. This dataset, NCT01107626-D1, contains baseline characteristics, treatment assignment, prior treatment, metastatic sites and efficacy data. Pemetrexed or bevacizumab is used for maintenance therapy of advanced no squamous non-small cell lung cancer (NSCLC). The combination of bevacizumab and pemetrexed has also demonstrated efficacy. This study contains two step registration, induction therapy step and maintenance therapy. All patients who were registered to at least one of the steps are included. Due to data cleaning efforts, data may contain slight discrepancies from that reported in Table 1 and Table 2 in the publication (PMID 31361535). The number of each metastatic site is incorrect in the publication: The data in this dataset is correct.
• NCT01107626-D2 (PMID 31361535): There are two different datasets for PMID 31361535 from trial E5508. This dataset, NCT01107626-D2, contains toxicity data. Pemetrexed or bevacizumab is used for maintenance therapy of advanced no squamous non‐small cell lung cancer (NSCLC). The combination of bevacizumab and pemetrexed has also demonstrated efficacy. This study contains two step registration, induction therapy step and maintenance therapy. All patients who were registered to at least one of the steps are included.

You are encouraged to view the PDF data dictionaries found in the “Documents” tab of the dbGaP study page, which may contain additional information regarding the data or the associated publication(s).

• Study Weblinks:
  • Trial webpage at clinicaltrials.gov
  • Primary publication at pubmed.ncbi.nlm.nih.gov/
• Study Design:
  • Clinical Trial
• Study Type:
  • Interventional
  • Metastasis
  • Multicenter
  • Phase III
  • Prospective
  • Randomized
  • Randomized Controlled Clinical Trial
• Total number of consented subjects: 1516
• Subject Sample Telemetry Report (SSTR)

• Clinical Trials
  • NCT01107626

Inclusion Criteria (Step 1 Induction Therapy):

• Cytologically or histologically confirmed non-small cell lung cancer (NSCLC)
• Predominant non-squamous histology (NSCLC not otherwise specified allowed). Mixed tumors are categorized by the predominant cell type.
• Stage IV disease including M1a or M1b stages or recurrent disease
• Stage IIIB (T4NX) disease with ipsilateral lung lobe allowed provided patients are not candidates for combined chemotherapy or radiotherapy
• At least 12 months since prior adjuvant chemotherapy
• At least 2 weeks since prior radiotherapy
• Prior carboplatin allowed provided it was given as part of adjuvant chemotherapy
• Patients with brain metastasis must have received local therapy to the brain and have no evidence of progression in the brain for at least 2 weeks from the time of completion of local therapy, prior to registration
• ECOG (Eastern Cooperative Oncology Group) performance status 0-1
• Leukocytes ≥ 3,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Total bilirubin ≤ institutional upper limit of normal (ULN)
• AST and ALT ≤ 3 times ULN
• Creatinine ≤ institutional ULN OR creatinine clearance ≥ 60 mL/min
• Urine protein:urine dipstick ≤ 0-1+ (if > 1+, urine protein creatinine ratio must be < 1)
• Measurable or non-measurable disease as defined by RECIST (Response Evaluation Criteria in Solid Tumours) criteria
• Patients with hypertension must be adequately controlled (BP < 150/100 mm Hg) with appropriate anti-hypertensive therapy or diet
• Concurrent therapeutic anti-coagulation allowed
• Fertile patients must agree to abstain from sexual intercourse or to use adequate contraceptive methods during and for at least 6 months after completion of study therapy

Exclusion Criteria (Step 1 Induction Therapy):

• Prior malignancy within the past 3 years except superficial melanoma, basal cell carcinoma, or carcinoma in situ
• Prior systemic chemotherapy for advanced stage lung cancer
• Prior use of paclitaxel, pemetrexed disodium, or bevacizumab
• Major hemoptysis within the past 4 weeks
• Uncontrolled intercurrent illness including, but not limited to, active infection, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, psychiatric illnesssocial situations that would limit compliance with study requirements
• History of arterial thrombotic events or major bleeding within the past 12 months
• Major surgery such as thoracotomy, laparotomy, craniotomy, or significant traumatic injury within 6 weeks prior to registration. Biopsy procedures and chest tube insertion are not considered major surgery for the purpose of this protocol.
• Core biopsy within 7 days of registration
• Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within the past 6 months
• Clinically significant cardiovascular disease
• Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
• History of serious non-healing wounds, ulcers, or bone fractures
• Cavitary lesions in the lungs
• Pregnant or nursing
• Concurrent anti-retroviral therapy in patients with HIV infection

Inclusion Criteria (Step 2 Maintenance Therapy):

• Patient must have an overall stable or better response after 4 courses of induction therapy
• ECOG (Eastern Cooperative Oncology Group) performance status 0-1
• Patients must be registered to Step 2 within 6 weeks of the last day of chemotherapy administration on Step 1
• Acceptable bone marrow, renal and hepatic function within 2 weeks of registration

• Primary Phenotype: Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms

• Study Chair
  • Suresh Ramalingam. Emory University, Atlanta, GA, USA.