Dose Escalating Study With BAY43-9006 With Carboplatin, Paclitaxel and Bevacizumab in Untreated Stage IIIb Non-small Cell Lung Cancer (NSCLC)

Bayer

Status and phase: Completed; Phase 1

Conditions: Carcinoma, Non-Small-Cell Lung; Lung Cancer

Treatments: Drug: Paclitaxel; Drug: Carboplatin; Drug: Nexavar (Sorafenib, BAY43-9006); Drug: Bevacizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT01069328

11956

Details and patient eligibility

About

To determine the tolerability, maximum tolerated dose and pharmacokinetics of this drug.

Enrollment: 33 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients must have Stage IIIB (with malignant pleural effusions) or Stage IV histological or cytological confirmation of non-small cell carcinoma (excluding squamous)

• Age >/= 18 years old

• Patients must have at least 1 evaluable lesion. Lesions must be evaluated by CT scan or MRI

• ECOG Performance Status of 0 to 1

• Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to start of first dose:

  • Hemoglobin >/= 9.0 g/dL
  • White blood cell (WBC) count >/= 2,500/mm3
  • Absolute neutrophil count (ANC) >/= 1,500/mm3
  • Platelet count >/= 100,000/mm3
  • Total bilirubin </= 1.5 times the upper limit of normal (ULN)
  • ALT and AST </= 2.5 X ULN (</= 5 X ULN for patients with liver involvement)
  • INR </= 1.5 and aPTT within normal limits
  • Serum creatinine </= ULN or creatinine clearance (CrCl) >/= 45 mL/min (CrCl = Wt (kg) x (140-age)/72 x Cr level, female x 0.85) for patients with creatinine levels above institutional normal
  • Urinalysis (UA) must show less than 1+ protein in urine, or the patient will require a repeat UA. If repeat UA shows 1+ protein or more, a 24 hour urine collection will be required and must show total protein </= 1000 mg/24 hour to be eligible

Exclusion criteria

• Patients with squamous histology
• Cardiac disease: Congestive heart failure > Class II NYHA; active coronary artery disease (MI more than 6 months prior to study entry is allowed); or serious cardiac ventricular arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted)
• Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg despite optimal medical management
• HIV infection or chronic hepatitis B or C
• Active clinically serious infections (> Grade 2 NCI-CTC Version 3.0)
• Evidence or history of CNS disease, including primary brain tumors, seizures disorders, or any brain metastasis

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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33 participants in 6 patient groups

Arm 1

Experimental group

Treatment:

Drug: Paclitaxel

Drug: Bevacizumab

Drug: Nexavar (Sorafenib, BAY43-9006)

Drug: Bevacizumab

Drug: Bevacizumab

Drug: Carboplatin

Drug: Bevacizumab

Drug: Nexavar (Sorafenib, BAY43-9006)

Arm 2

Experimental group

Treatment:

Drug: Paclitaxel

Drug: Bevacizumab

Drug: Nexavar (Sorafenib, BAY43-9006)

Drug: Bevacizumab

Drug: Bevacizumab

Drug: Carboplatin

Drug: Bevacizumab

Drug: Nexavar (Sorafenib, BAY43-9006)

Arm 3

Experimental group

Treatment:

Drug: Paclitaxel

Drug: Bevacizumab

Drug: Nexavar (Sorafenib, BAY43-9006)

Drug: Bevacizumab

Drug: Bevacizumab

Drug: Carboplatin

Drug: Bevacizumab

Drug: Nexavar (Sorafenib, BAY43-9006)

Arm 4

Experimental group

Treatment:

Drug: Paclitaxel

Drug: Bevacizumab

Drug: Nexavar (Sorafenib, BAY43-9006)

Drug: Bevacizumab

Drug: Bevacizumab

Drug: Carboplatin

Drug: Bevacizumab

Drug: Nexavar (Sorafenib, BAY43-9006)

Arm 5

Experimental group

Treatment:

Drug: Paclitaxel

Drug: Bevacizumab

Drug: Nexavar (Sorafenib, BAY43-9006)

Drug: Bevacizumab

Drug: Bevacizumab

Drug: Carboplatin

Drug: Bevacizumab

Drug: Nexavar (Sorafenib, BAY43-9006)

Arm 6

Experimental group

Treatment:

Drug: Paclitaxel

Drug: Bevacizumab

Drug: Nexavar (Sorafenib, BAY43-9006)

Drug: Bevacizumab

Drug: Bevacizumab

Drug: Carboplatin

Drug: Bevacizumab

Drug: Nexavar (Sorafenib, BAY43-9006)