Docetaxel or Pemetrexed With or Without Cetuximab in Patients With Recurrent or Progressive Non-Small Cell Lung Cancer
Condition: Non Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Pemetrexed; Cetuximab; Docetaxel
Intervention description: Pemetrexed 500 mg/m^2 administered intravenously on Day 1 of 3 weeks cycle until disease progression or unacceptable toxicity for up to six (3-week) cycles.; Cetuximab 400/250 mg/m^2 (initial/weekly) administered intravenously on Days 1, 8, and 15 (3-week) cycles until disease progression or unacceptable toxicity.; Docetaxel 75 mg/m^2 administered intravenously on Day 1 of 3 weeks cycle until disease progression or unacceptable toxicity for up to six (3-week) cycles.
Intervention MeSH terms: Docetaxel; Pemetrexed; Cetuximab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 939.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Recurrent or Progressive Non-Small Cell Lung Cancer; Second-line therapy; Docetaxel; Pemetrexed; Cetuximab; Failed platinum-based therapy; NSCLC

Summary:

      This trial is a multicenter, open-label, randomized, Phase III study in patients with
      recurrent or progressive Non-Small Cell Lung Cancer (NSCLC) after failure of an initial
      platinum-based chemotherapy. Patients will receive either Docetaxel or Pemetrexed as
      chemotherapy at the investigator's choice. Within each chemotherapy group, patients will be
      randomized to receive Cetuximab plus chemotherapy or chemotherapy alone (Cetuximab &
      Pemetrexed or Pemetrexed alone; Cetuximab & Docetaxel or Docetaxel alone).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Pathologic confirmation of metastatic, unresectable, or locally-advanced NSCLC.

          -  Disease progression during or following one prior platinum-based chemotherapy regimen
             for advanced disease (stage IIIB or IV).

          -  Bidimensionally measurable disease.

          -  Karnofsky performance status score of 60 to 100 at study entry.

          -  The participant has tumor tissue available for immunohistochemical determination of
             epidermal growth factor (EGFR) expression.

          -  Adequate recovery from recent surgery, chemotherapy, and radiation therapy. At least 4
             weeks must have elapsed from major surgery, prior chemotherapy, prior treatment with
             an investigational agent, or prior radiation therapy (palliative radiation therapy is
             allowed).

          -  Accessible for treatment and follow-up. Participants enrolled in this trial must be
             treated at the participating center.

          -  Women of childbearing potential (WOCBP) and fertile men with partners of childbearing
             potential must be using an adequate method of contraception.

          -  WOCBP must have a negative serum or urine pregnancy test.

        Exclusion Criteria:

          -  Women who are pregnant or breastfeeding.

          -  Dementia, altered mental status, or any psychiatric condition that would prohibit the
             understanding or rendering of informed consent.

          -  A serious uncontrolled medical disorder that would impair the ability of the patient
             to receive protocol therapy.

          -  Symptomatic or uncontrolled metastases in the brain. Participants receiving a
             glucocorticoid for brain metastases will be excluded, but those receiving
             anticonvulsants will be eligible.

          -  Uncontrolled pleural effusion or ascites.

          -  Peripheral neuropathy greater than grade 2, as assessed by the National Cancer
             Institutes-Common Toxicity Criteria Adverse Events (NCI-CTCAE), Version 3.0.

          -  Any concurrent malignancy other than basal cell skin cancer, or carcinoma in situ of
             the cervix. Patients with a previous malignancy, but without evidence of disease for
             greater than or equal 3 years will be allowed to enter the trial.

          -  More than one prior chemotherapy regimen for advanced disease.

          -  Inadequate hematologic function defined by an absolute neutrophil count (ANC)
             <1,500/mm3, a platelet count <100,000/mm3, and a hemoglobin level <9 g/dL. Red blood
             cell transfusions are not permitted within 7 days of receiving cetuximab, docetaxel,
             or pemetrexed.

          -  Inadequate hepatic function, defined by a total bilirubin level >1.5 times the upper
             limit of normal (ULN), aspartate transaminase (AST) and alanine aminotransferase (ALT)
             levels >2.5 times the ULN (greater than or equal to 5 times the ULN if known liver
             metastases), and an alkaline phosphatase level >5.0 times the ULN.

          -  Inadequate renal function defined by a serum creatinine level >1.5 times the ULN.

          -  Prior treatment with cetuximab, or any other epidermal growth factor receptor
             inhibitors, including tyrosine kinase inhibitors, such as gefitinib or erlotinib.
             Participants must not have received prior chimerized or murine monoclonal antibody
             therapy. Prior treatment with other monoclonal antibodies targeting receptors other
             than the EGFR is permitted >30 days prior to randomization.

          -  Prior treatment with docetaxel or pemetrexed therapy.

          -  Inability or unwillingness to take folic acid or vitamin B12 supplementation.

          -  Inability or unwillingness to interrupt nonsteroidal anti-inflammatory drugs (NSAIDs)
             for a 5-day period (8-day period for long-acting agents such as piroxicam). Aspirin
             will be permitted during the study.

          -  Patients (including prisoners) who are compulsorily detained (involuntarily
             incarcerated) for treatment of either a psychiatric or physical (eg, infectious
             disease) illness.

          -  Prior treatment with an experimental drug or medical device within 30 days of
             randomization.