MK-0646 IMPACT Study: MK-0646, Insulin Growth Factor 1 Receptor Antibody in Stage IIIB or IV Metastatic Non-Squamous Lung Cancer, Combined With Pemetrexed (Alimta) and Cisplatin, a Randomized Phase II Trial.
- histologically or cytologically proven newly diagnosed Stage IlIB or Stage IV
advanced primary non-small cell bronchogenic lung cancer (non-squamous cell to
include bronchoalveolar, adenocarcinoma, large cell carcinoma, or unspecified).
- clinically significant pleural effusion must have a thoracentesis.
- Patients with brain metastases are eligible provided they have completed brain
radiation, neurologically stable, off dexamethasone for at least 1 week prior to
registration. Patients with asymptomatic brain metastatic disease are eligible if
they do not require radiation and are neurologically stable without dexamethasone.
- measurable disease documented by CT, MRI, X-ray or physical exam. Measurable disease
must be assessed within 28 days prior to registration. Pleural effusions, ascites and
laboratory parameters are not acceptable as the only evidence of disease.
Non-measurable disease must be assessed within 28 days prior to registration. All
disease must be assessed and documented.
- Prior radiation is permitted; at least one week must have elapsed since the
completion of prior radiation therapy and must have recovered from all associated
toxicities at time of registration. Measurable or non-measurable disease must be
outside the previous radiation field or a new lesion must be present.
- At least 4 weeks have elapsed since surgery (thoracic or other major surgeries) and
patients have recovered from all associated toxicities at the time of registration.
Measurable disease must be present outside the area of surgical resection. There must
be no anticipation of need for major surgical procedures during protocol treatment.
- Age ≥ 18 years old.
- ECOG performance status of 0-1.
- adequate bone marrow function defined by platelet count at least 100,000/mm3,
hemoglobin ≥ 9g/dl, leukocyte count at least 3,000/mm OR absolute neutrophil count at
- adequate hepatic function documented by serum bilirubin ≤ 1.5x upper normal limit,
AST or ALT, and alkaline phosphatase all ≤ 3 x IULN within 28 days prior to
registration. (Except in presence of known hepatic metastasis, wherein AST or ALT may
be up to 5 X upper normal limit.)
- serum creatinine ≤ institutional upper limit of normal (IULN) AND calculated or
measured creatinine clearance ≥ 50 ml/mm using the Cockcroft Gault Formula. These
tests must have been performed within 28 days prior to registration.
- ability to give informed consent.
- Able to provide consent for gene expression profiling, histopathology, and/or
- Women of childbearing potential must have negative serum pregnancy test.
- Patients taking NSAIDs must agree to interrupt NSAIDS 2 days before (5 days for
long-acting NSAIDs), the day of, and 2 days following administration of pemetrexed.
- ability to take folic acid, Vitamin B12, and dexamethasone according to protocol.
- Prior systemic chemotherapy or biologic therapy for non-small cell lung cancer. If
neoadjuvant therapy or adjuvant therapy was given, patient must be at least 1 year
out from the last chemotherapy and fully recovered from all toxicities.
- Cardiovascular: uncontrolled congestive heart failure, high blood pressure, unstable
angina, or myocardial infarction within the prior year,serious cardiac arrhythmias
- Serious uncontrolled active infection, acute hepatitis or known HIV.
- Prior history of severe allergy (grade 3 or 4) to human monoclonal antibody.
- Concurrent use of human growth hormone or growth hormone inhibitors.
- Uncontrolled diabetes mellitus defined as a Hemoglobin A1C≥ 7.
- An other active malignancy in the past 2 years.
- Pregnant or nursing women are not eligible to participate in this trial due to the
potential teratogenic or abortifacient effects of the study drug on the fetus or
nursing infant. Persons of reproductive potential must have agreed to use two methods
of effective contraception prior to, during, and for 4 weeks after study therapy.