Clinical Research Details

A Randomized, Phase III Study Comparing Carboplatin/Paclitaxel or Carboplatin/Paclitaxel/Bevacizumab with or without COncurrent Cetuximab in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC) Protocol S0819 Version Date: 7/29/09

The primary objective of this study is:

In patients with advanced NSCLC treated with carboplatin, paclitaxel and bevacizumab (if appropriate) with or without cetuximab, to compare: a. Overall survival (OS) in the entire study population b. Progression-free survival (PFS) by institutional review in EGFR FISH-positive patients

The secondary objectives are:

In patients with advanced NSCLC treated with carboplatin, paclitaxel and bevacizumab (if appropriate) with or without cetuximab, to compare: a. OS and PFS by centralized review in EGFR FISH-positive patients b. PFS by centralized image review and by institutional review in the entire study population

To compare the response rate (confirmed plus unconfirmed, complete and partial responses) in the subset of patients with measurable disease in: a. EGFR FISH-positive patients b. The entire study population

To assess the toxicities of these treatment regimens

To prospectively test EGFR FISH as a predictive marker for the selection of patients for cetuximab plus chemotherapy

To evaluate the role of KRAS mutations in terms of cetuximab efficacy

To compare the results of EGFR FISH with KRAS mutations, EGFR mutations, EGFR IHC and other purported EGFR-related biomarkers

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Patients must have histologically or cytologically proven newly diagnosed Stage IV, as defined in Section 4.0, advanced primary non-small cell lung cancer (adenocarcinoma, large cell carcinoma, squamous or unspecified) or recurrent disease after previous surgery and/or irradiation. Patients with additional lesions in an ipsilateral non-primary lobe without M1a or M1b disease will not be considered to have Stage IV disease and are not eligible.
5.2 Patients with controlled (for a minimum of two months) brain metastases after treatment and no residual neurological dysfunction off corticosteroids are eligible. All patients must have a pretreatment CT or MRI scan of the brain to evaluate for CNS disease within 42 days prior to registration.
5.3 Patients may have measurable or non-measurable disease (see Section 10.1)
documented by CT or MRI. The CT from a combined PET/CT may be used to document only non-measurable disease unless it is of diagnostic quality as defined in Section 10.1a. Measurable disease must be assessed within 28 days prior to registration. Pleural effusions, ascites and laboratory parameters are not acceptable as the only evidence of disease. Non-measurable disease must be assessed within 42 days prior to registration. All disease must be assessed and documented on the Baseline Tumor Assessment Form (Form #848). See Sections 15.2 and 19.6 for guidelines and submission instructions for required central radiology review.
5.4 Translational medicine studies: Patients must agree to submission of specimens for EGFR FISH testing and other translational medicine studies as outlined in Section 15.0.
Patients must be offered participation in banking for future research.
5.5 Patients must not have received for any purpose prior chemotherapy, cetuximab, gefitinib, erlotinib or other investigational agents that target the EGFR pathway. Patients must not have received for any purpose prior VEGF-related agents. Patients must not have received for any purpose prior chimerized or murine monoclonal antibody therapy or have documented presence of human anti-mouse antibodies (HAMA).
5.6 Prior radiation is permitted; however, patients must have recovered from all associated toxicities at time of registration. In order to qualify as measurable per Section 10.1a, measurable disease must be outside the previous radiation field or must have progressed.
Open biopsy or significant traumatic injury and patients must have recovered from all associated toxicities at the time of registration. There must be no anticipation of need for major surgical procedures during protocol treatment. Patients must not have had a core biopsy within seven days prior to registration.
5.8 Patients must have an ANC = 1,500/mcl, platelet count = 100,000/mcl and hemoglobin =9 mg/dL obtained within 14 days prior to registration.
5.9 Patients must have a serum creatinine = institutional upper limit of normal (IULN) AND calculated or measured creatinine clearance = 50 cc/min using the following Cockroft-Gault Formula:
Estimated creatinine clearance = (140 - age) X (actual body weight in kg).
72 x serum creatinine. Multiply this number by 0.85 if the patient is a female.
These tests must have been performed within 14 days prior to registration.
5.10 Urine protein must be screened by urine analysis for urine protein creatinine (UPC) ratio. For UPC ratio > 0.5, 24-hour urine protein must be obtained and the level must be< 1,000 mg for patient enrollment. The urine protein used to calculate the UPC ratio must be obtained within 14 days prior to registration.

You will be randomized to receive either chemotherapy without cetuximab or chemotherapy with cetuximab. Randomization means that you are put into a group by chance. A computer program will place you in one of the study groups. Neither you nor your doctor can choose the group you will be in. You will have an equal chance of being placed in either group to receive cetuximab or not. The decision about whether you will receive bevacizumab will be made by you and your doctor based on several considerations related to your health history.

If you are in Group 1, you will have six three-week cycles of chemotherapy with paclitaxel, carboplatin and bevacizumab. All of these are given by IV (through your veins). You will receive the drugs once every three weeks. You will receive the paclitaxel over three hours. Right after that, you will receive the carboplatin over 30 minutes. Finally, one hour after that, you will receive the bevacizumab. The first time you receive bevacizumab, it will take about 90 minutes. Your doctor may be able to shorten this for future treatments if you tolerate it well. Total time to receive treatment in the first cycle will be about seven hours for all of the drugs. Later cycles may be a bit shorter.

If you are in Group 2, you will have six three-week cycles of chemotherapy with paclitaxel and carboplatin. These are given by IV (through your veins). You will receive the drugs once every three weeks. You will receive the paclitaxel over three hours. Right after that, you will receive the carboplatin over 30 minutes. Total time to receive treatment in the first cycle will be about three to four hours for both of the drugs.

If you are in Group 3, you will have six three-week cycles of chemotherapy with cetuximab, paclitaxel, carboplatin and bevacizumab. All of these are given by IV (through your veins). You will receive cetuximab once per week and the other drugs once every three weeks. The cetuximab will take about one hour. After a one hour break, you will receive the paclitaxel over three hours. Right after that, you will receive the carboplatin over 30 minutes. Finally, one hour after that, you will receive the bevacizumab. The first time you receive bevacizumab, it will take about 90 minutes. Your doctor may be able to shorten this for future treatments if you tolerate it well.

If you are in Group 4, you will have six three-week cycles of chemotherapy with cetuximab, paclitaxel and carboplatin. All of these are given by IV (through your veins). You will receive cetuximab once per week and the other drugs once every three weeks. The cetuximab will take about one hour. After a one hour break, you will receive the paclitaxel over three hours. Right after that, you will receive the carboplatin over 30 minutesTotal time to receive treatment in the first cycle will be five to six hours for all of the drugs.

Kathy S. Albain, M.D.

(708) 327-3229