Randomized, Double-Blind Trial of Erlotinib/Pazopanib or Erlotinib/Placebo in Patients With Previously Treated Advanced Non-Small-Cell Lung Cancer
Condition: Non Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Pazopanib; Erlotinib
Intervention description: Pazopanib: 600 mg orally daily; Erlotinib: 150 mg orally daily
Intervention MeSH terms: Erlotinib Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 202.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Lung Cancer; Previously Treated Advanced Non Small Cell Lung Cancer; Erlotinib; Pazopanib

Summary:

      This randomized, placebo-controlled, Phase II trial will compare the combination of erlotinib
      with pazopanib (providing concurrent EGFR and VEGFR inhibition) with erlotinib alone in the
      second- or third-line treatment of patients with advanced NSCLC. This study will be conducted
      though the Sarah Cannon Research Consortium, a community-based clinical trial network.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Pathologic confirmation of stage IIIB/IV NSCLC (squamous carcinoma, adenocarcinoma, or
             large cell carcinoma) per the American Joint Committee on Cancer Cancer Staging
             Manual, 6th edition. Patients with mixed tumors with small- cell elements are
             ineligible.

          2. At least one lesion that can be accurately measured in at least one dimension (longest
             diameter to be recorded) as >20 mm with conventional techniques, or as >10 mm with
             spiral computerized tomography scan according to the Response Evaluation Criteria in
             Solid Tumors version 1.1 (Eisenhauer et al. 2009)

          3. Failure of at least 1, and no more than 2, prior chemotherapy regimens for advanced
             disease (either due to progressive disease or toxicity).

          4. Recovery from any toxic effects of prior therapy to ≤ grade 1 per the National Cancer
             Institute Common Terminology Criteria for Adverse Events (NCI CTCAE).

          5. Completion of radiation therapy at least 28 days prior to the start of study treatment
             (not including palliative local radiation). Previously irradiated lesions in the
             advanced setting cannot be included as target lesions unless clear tumor progression
             has been observed since the end of radiation.

          6. ECOG Performance Status of 0-2.

          7. Adequate hematologic, hepatic and renal function.

          8. A female is eligible to enter and participate in this study if she is of:

               -  non-childbearing potential (i.e., physiologically incapable of becoming
                  pregnant), including any female who has had hysterectomy, bilateral oophorectomy
                  (ovariectomy), bilateral tubal ligation, is post-menopausal

               -  childbearing potential, including any female who has had a negative serum
                  pregnancy test within 1 week prior to the first dose of study treatment,
                  preferably as close to the first dose as possible, and agrees to use adequate
                  contraception.

          9. Patients entering the study must be willing to provide a serum sample at baseline and
             at off-study for disease progression for correlative serum proteomic testing.

         10. Willingness to provide a plasma sample at baseline, and at off-study for disease
             progression for correlative testing of circulating plasma biomarkers.

         11. Patients entering this study must be willing to provide tissue from a previous tumor
             biopsy (if available) for correlative tissue testing.

         12. Patients must be able to understand the nature of this study, give written informed
             consent, and comply with study requirements.

        Exclusion Criteria:

          1. Past or current history of neoplasm (other than the entry diagnosis), with the
             exception of treated non-melanoma skin cancer or carcinoma in-situ of the cervix, or
             other cancers cured by local therapy alone, and a disease-free survival ≥3 years.

          2. Prior treatment with EGFR tyrosine kinase inhibitors or vascular endothelial factor
             receptor tyrosine kinase inhibitors for NSCLC. [Note: prior bevacizumab (Avastin®) use
             is permitted].

          3. Prior use of an investigational agent within 28 days or 5 half-lives, whichever is
             longer, prior to the first dose of study drug.

          4. History of any one or more of the following cardiovascular conditions within the past
             6 months:

               -  Cardiac angioplasty or stenting

               -  Myocardial infarction

               -  Unstable angina

               -  Coronary artery bypass graft surgery

               -  Symptomatic peripheral vascular disease

               -  Class III or IV congestive heart failure, as defined by New York Heart
                  Association classification

          5. History or clinical evidence of central nervous system (CNS) metastases or
             leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS
             metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure
             medication for 1 week prior to first dose of study drug. Screening with CNS imaging
             (CT or magnetic resonance imaging) is required only if clinically indicated or if the
             subject has a history of CNS metastases.

          6. Women who are pregnant or lactating. All females of childbearing potential must have
             negative serum or urine pregnancy tests within 7 days prior to study treatment.

          7. Poorly controlled hypertension [defined as systolic blood pressure of ≥150 mmHg or
             diastolic blood pressure of ≥90mmHg].

          8. Presence of uncontrolled infection.

          9. Prolongation of heart rate-corrected QT interval (QTc) ≥480 msec (using Bazett's
             formula).

         10. Use of any of the medications on the prohibited medication list within 14 days of
             study treatment (with the exception of Amiodarone, which is prohibited from 6 months
             prior to screening through discontinuation from the study).

         11. A serious underlying medical condition that would impair the ability of the patient to
             receive protocol treatment.

         12. Prior major surgery or trauma within 28 days prior to first dose of study drug and/or
             presence of any non-healing wound, fracture, or ulcer (procedures such as catheter
             placement not considered to be major).

         13. Minor surgical procedures (with the exception of the placement of portacath or other
             central venous access) performed less than 7 days prior to beginning protocol
             treatment.

         14. History of cerebrovascular accident including transient ischemic attack (TIA),
             pulmonary embolism (PE), or untreated DVT within the past 6 months.

         15. Previous treatment with cetuximab.

         16. Patients with hemoptysis or tumor cavitation at baseline.

         17. Any prior history of hypertensive crisis or hypertensive encephalopathy.

         18. Pulmonary hemorrhage/bleeding event within 6 weeks prior to beginning study treatment.

         19. Any other non-pulmonary hemorrhage/bleeding event ≥ grade 3 within 28 days of study
             treatment.

         20. Evidence or history of bleeding diathesis.

         21. Serious non-healing wound, ulcer, or bone fracture.

         22. Known or suspected allergy/hypersensitivity to any agent given in the course of this
             trial.

         23. Clinically significant gastrointestinal (GI) abnormalities.