An Open-label, Multicenter, Randomized Phase 2 Study Evaluating the Safety and Efficacy of Cisplatin and Pemetrexed With or Without Cixutumumab as First-Line Therapy in Patients With Advanced Nonsquamous Non-Small Cell Lung Carcinoma
- The patient has histologically or cytologically confirmed, nonsquamous
(adenocarcinoma/large cell or other) NSCLC.
- The patient has Stage IV disease at the time of study entry.
- Patients 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 patient 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 patient has measurable or nonmeasurable disease according to Response Evaluation
Criteria In Solid Tumors (RECIST) Version 1.1 guidelines.
- The patient 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 patient has adequate bone marrow reserve, and renal and hepatic function
- The patient 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 patient 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 patient has archived tumor tissue available for analysis (can be either primary
tumor or metastases).
- The patient has an estimated life expectancy of at least 12 weeks.
- 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.
- Patients who have squamous histology.
- The patient's tumor fully or partially contains Small Cell Lung Cancer (SCLC).
- The patient has leptomeningeal disease.
- The patient is currently or has previously received chemotherapy for advanced (Stage
- The patient has a history of treatment with other agents targeting the Insulin-like
or Epidermal Growth factor receptors.
- Patients who have received prior Pemetrexed treatment.
- The patient has a known allergy/history of hypersensitivity reaction to any of the
- The patient has diabetes mellitus as defined by being treated with glucose lowering
medications in the past 3 months prior to enrollment.
- The patient 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
- The patient has an ongoing or active infection requiring parenteral antibiotic,
antifungal, or antiviral therapy.
- The patient has undergone major surgery within 28 days prior to randomization.
- The patient has received a prior autologous or allogeneic organ or tissue
- The patient is pregnant or lactating.
- The patient 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 patient has superior vena cava syndrome contraindicating hydration.
- The patient has current clinically-relevant coronary artery disease (New York Heart
Association III or IV) or uncontrolled congestive heart failure.
- The patient has any Grade 2 (or greater) peripheral neuropathy.
- The patient 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 patient 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 patient is unwilling or unable to take premedications (folic acid, vitamin B12,
or corticosteroids) required by the pemetrexed label.
- The patient has received a recent (within 30 days of enrollment) or is receiving
concurrent yellow fever vaccination.