A Phase I/II Trial of AMG 102 and Erlotinib in Previously Treated Patients With Advanced Non-Small Cell Lung Cancer
Patients must have baseline evaluations performed prior to the first dose of study drug
and must meet all inclusion and exclusion criteria. Results of all baseline evaluations,
which assure that all inclusion and exclusion criteria have been satisfied, must be
reviewed by a Physician Investigator prior to enrollment of that patient. In addition, the
patient must be thoroughly informed about all aspects of the study, including the study
visit schedule and required evaluations and all regulatory requirements for informed
consent. The written informed consent must be obtained from the patient prior to
enrollment. The following criteria apply to all patients enrolled onto the study unless
- Patients with recurrent or progressive advanced stage Non-small cell lung cancer
(NSCLC,no SCLC component) who have been treated with at least one and a maximum of
two prior chemotherapy regimens for advanced NSCLC. Chemotherapy as part of initial
potentially curative therapy (given as part of adjuvant or concomitant
chemoradiotherapy) that was completed <1 year counts as 1 prior regimen. Prior
erlotinib, other epidermal growth factor receptor (EGFR) TKIs or monoclonal
antibodies targeting EGFR are not allowed.
NOTE: Chemotherapy as part of initial potentially curative therapy (given as part of
adjuvant or concomitant chemoradiotherapy) that was completed one or more years prior to
screening for this study does not count as a prior regimen.
If the tumor is refractory (progressed) after a prior chemotherapy regimen, then that
regimen would count. If a prior chemotherapy regimen has been changed due to other reasons
than disease progression (e.g. poor tolerance, allergic reaction), then it would not count
as a separate prior regimen. A chemotherapy drug added for "maintenance" following disease
stabilization or response to a chemotherapy regimen (in the absence of prior disease
progression) does not count as a separate prior regimen.
- Measurable disease (RECIST version 1.1) (for phase II part only).
- Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2 and life
expectancy of ≥ 3 months.
NOTE: For the phase I part of the study, patients with ECOG Performance Status 2 will be
- Age ≥ 18 years old and ability to provide written informed consent obtained prior to
participation in the study and any related procedures being performed.
- Patients must meet the following laboratory criteria (within 14 days prior to study
Absolute neutrophil count (ANC) ≥ 1500/mm³ Platelets ≥ 100,000/mm³ Hemoglobin ≥ 9 g/dL
International normalized ratio (INR) ≤ 1.5 or prothrombin time (PT)/partial thromboplastin
time (PTT) within normal limits (WNL) of the institution
o Biochemistry: Total Bilirubin within normal institutional limits. AST/SGOT and ALT/SGPT
≤ 2.5 x upper limit of normal (ULN), except if there is known hepatic metastasis, wherein
transaminases may be ≤ 5 x institutional ULN.
Creatinine clearance 45 ml/min or higher calculated using the Cockcroft-Gault formula.
Multiply the number by 0.85 if the patient is female.
- Patients must have fully recovered from the effects of any prior surgery,
chemotherapy or radiation therapy. In the case of residual effects, these must be
clinically stable, grade 1 or less in severity and do not meet other protocol
exclusion criteria. A minimum time period of 3 weeks should elapse between the
completion of radiation therapy for recurrent/metastatic disease and enrollment in
the study. A minimum of 4 weeks should elapse between the completion of chemotherapy
or any experimental therapy and enrollment in the study. A minimum of 4 weeks should
elapse between prior major surgery (such as open biopsy or significant traumatic
injury) and enrollment in the study. A minimum of 2 weeks should elapse between prior
minor surgical procedures (such as chemotherapy infusion port placement or core
visceral organ biopsy) and enrollment in the study.
- If patient has history of brain metastases, brain lesions should have been treated
with surgery and/or radiation and be stable on repeat imaging and patients should be
neurologically stable on a stable or tapering dose of corticosteroids.
- No history of prior malignancy, with the exception of curatively treated squamous
cell or basal carcinoma of the skin or in situ cervical cancer, unless there is a
3-year disease-free interval.
- Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy
test within 7 days of the first administration of study treatment and must be willing
to use two methods of contraception one of them being a barrier method or abstain
from sexual activity during the study and for 6 months after last study drug
administration. Sexually active males and their female partners must agree to use two
methods of accepted and effective method of contraception (hormonal or barrier
methods, abstinence) prior to study entry and for the duration of the study.
- All patients must have given signed, informed consent prior to registration on study.
- Patients with known positivity for human immunodeficiency virus (HIV) or hepatitis C;
baseline testing for HIV and hepatitis C is not required. This is due to the unknown
effects of AMG102.
- Patients with any significant history of non-compliance to medical regimens or with
inability to grant a reliable informed consent.
- Patients who have mixed tumors with small-cell elements are ineligible.
- Pregnancy or lactation. All females of child-bearing potential must have negative
serum or urine pregnancy tests within 7 days prior to starting study treatment.
- Prior treatment of NSCLC with EGFR TKIs or monoclonal antibodies targeting EGFR.
- A serious active infection (>grade 2) within 7 days of enrollment.
- A serious underlying medical condition that would impair the ability of the patient
to receive protocol treatment.
- Untreated brain metastases.
- A major surgical procedure or significant traumatic injury within 28 days of
beginning treatment, or anticipation of the need for major surgery during the course
of the study per inclusion criterion 3.1. In addition, if a patient has not yet
recovered from prior minor surgery (such as central venous access device or fine
needle aspiration biopsy).
- Thrombosis or vascular ischemic events within the last twelve months, such as deep
venous thrombosis, pulmonary embolism, transient ischemic attack, cerebral
infarction, or myocardial infarction
- Concurrent or prior (within 7 days of enrollment) anticoagulation therapy, except for
the use of low dose coumarin-type anticoagulants or low molecular weight heparin for
prophylaxis against central venous catheter thrombosis
- Presence of peripheral edema > Grade 2 (CTCAE version 4).