A Study in Non-Small Cell Lung Cancer
Condition: Non-Small-Cell Lung Carcinoma
MeSH terms: Carcinoma; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Pemetrexed; Cisplatin; Cixutumumab
Intervention description: Administered intravenously (IV); Administered IV; Administered IV
Intervention MeSH terms: Pemetrexed
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 172.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: lung cancer; advanced; non-small cell

Summary:

      The primary purpose of this study is to evaluate the hypothesis that cixutumumab given in
      combination with cisplatin and pemetrexed is superior to cisplatin and pemetrexed as
      first-line therapy for patients with advanced nonsquamous non-small cell lung carcinoma
      (NSCLC).
    

Eligibility criteria:

        Inclusion Criteria:

          -  The participant has histologically or cytologically confirmed, nonsquamous
             (adenocarcinoma/large cell or other) NSCLC.

          -  The participant has Stage IV disease at the time of study entry.

          -  Participants with treated brain metastases are eligible if they are clinically stable
             with regard to neurologic function, off steroids after cranial irradiation (whole
             brain radiation therapy, focal radiation therapy, and stereotactic radiosurgery)
             ending at least 14 days prior to randomization, or after surgical resection performed
             at least 28 days prior to randomization. The participant may have no evidence of Grade
             1 (or greater) Central Nervous System (CNS) hemorrhage based on pretreatment
             scans(performed within 21 days before randomization).

          -  The participant has measurable or nonmeasurable disease according to Response
             Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 guidelines.

          -  The participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status
             (PS) of 0 or 1.

          -  If prior adjuvant or neoadjuvant chemotherapy, the last dose of adjuvant or
             neoadjuvant treatment was administered at least 6 months prior to randomization.

          -  The participant has adequate bone marrow reserve, and renal and hepatic function

          -  The participant has fasting serum glucose less than or equal to 125 mg/dL, and
             hemoglobin A1C less than or equal to 6%.

          -  Females with reproductive potential: Must have a negative serum or urine pregnancy
             test within 7 days prior to the first dose of any study drug.

          -  Males and females with reproductive potential: Must agree to use medically approved
             contraceptive precautions during the study and for 6 months following the last dose of
             any study drug.

          -  The participant has the ability to understand and the willingness to sign a written
             informed consent form.

          -  Previous radiation therapy is allowed to less than 25% of the bone marrow, but should
             have been limited and must not have included whole pelvis radiation.

          -  The participant has archived tumor tissue available for analysis (can be either
             primary tumor or metastases).

          -  The participant has an estimated life expectancy of at least 12 weeks.

        Exclusion Criteria:

          -  Are currently enrolled in, or discontinued within the last 30 days from, a clinical
             trial involving an investigational drug or device or off-label use of a drug or
             device, or concurrently enrolled in any other type of medical research judged not to
             be scientifically or medically compatible with this study.

          -  Participants who have squamous histology.

          -  The participant's tumor fully or partially contains Small Cell Lung Cancer (SCLC).

          -  The participant has leptomeningeal disease.

          -  The participant is currently or has previously received chemotherapy for advanced
             (Stage IV) NSCLC.

          -  The participant has a history of treatment with other agents targeting the
             Insulin-like or Epidermal Growth factor receptors.

          -  Participants who have received prior Pemetrexed treatment.

          -  The patient has a known allergy/history of hypersensitivity reaction to any of the
             treatment components.

          -  The participant has diabetes mellitus as defined by being treated with glucose
             lowering medications in the past 3 months prior to enrollment.

          -  The participant has an uncontrolled intercurrent illness including, but not limited
             to, ongoing or active infection requiring parenteral antibiotics, symptomatic
             congestive heart failure, uncontrolled hypertension, clinically significant cardiac
             arrhythmia,or psychiatric/social situations that would limit compliance with study
             requirements.

          -  The participant has an ongoing or active infection requiring parenteral antibiotic,
             antifungal, or antiviral therapy.

          -  The participant has undergone major surgery within 28 days prior to randomization.

          -  The participant has received a prior autologous or allogeneic organ or tissue
             transplantation.

          -  The participant is pregnant or lactating.

          -  The participant has a history of another primary cancer, with the exception of the
             following: curatively resected nonmelanomatous skin cancer, curatively treated
             carcinoma in situ, or other primary solid tumor treated with curative intent and no
             known active disease present and no treatment administered during the last 5 years.

          -  The participant has superior vena cava syndrome contraindicating hydration.

          -  The participant has current clinically-relevant coronary artery disease (New York
             Heart Association III or IV) or uncontrolled congestive heart failure.

          -  The participant has any Grade 2 (or greater) peripheral neuropathy.

          -  The participant has clinically significant third-space fluid collections, for example,
             ascites or pleural effusions that cannot be controlled by drainage or other procedures
             prior to study entry.

          -  The participant is unable to interrupt aspirin or other nonsteroidal anti-inflammatory
             agents, other than an aspirin dose less than or equal to 1.3 grams per day, for a
             5-day period (8-day period for long-acting agents, such as piroxicam).

          -  The participant is unwilling or unable to take premedications (folic acid, vitamin
             B12, or corticosteroids) required by the pemetrexed label.

          -  The participant has received a recent (within 30 days of enrollment) or is receiving
             concurrent yellow fever vaccination.