A Phase II Study of Pertuzumab and Erlotinib for Metastatic or Unresectable Neuroendocrine Tumors

Inclusion Criteria: Subjects must be treated at Stanford University Medical Center for the entire length of study participation. 1. Patients must have histologically or cytologically confirmed well-differentiated neuroendocrine tumor. Patients must be deemed unresectable due to involvement of critical vasculature or adjacent organ invasion or have metastatic disease. 2. Patients with prior surgical resection who develop radiological or clinical evidence of metastatic cancer do not require separate histological or cytological confirmation of metastatic disease unless an interval of \> 5 years has elapsed between the primary surgery and the development of metastatic disease. Clinicians should consider biopsy of lesions to establish diagnosis of metastatic disease if there is substantial clinical ambiguity regarding the nature or source of apparent metastases. 3. Prior chemotherapy will be permitted. 4. Prior or concurrent somatostatin analogue use will be permitted. 5. Patients must have a primary or metastatic lesion measurable in at least one dimension by Modified RECIST criteria (v1.1) within 4 weeks prior to entry of study. 6. Patients must have ECOG performance status of 0-2. 7. Patients must be \>= 18 years of age. 8. Laboratory values \<= 2 weeks prior to randomization: * Absolute Neutrophil Count (ANC) \>= 1.5 x 109/L (\>= 1500/mm3) * Platelets (PLT) \>= 50 x 109/L (\>= 100,000/mm3) (or \>= 25 x 109/L (\>= 100,000/mm3) if thrombocytopenia is secondary to a non-myelosuppressive cause such as splenic sequestration). * Hemoglobin (Hgb) \>= 9 g/dL * Serum creatinine \<= 1.5 x ULN * Serum bilirubin \<= 1.5 x ULN (\<= 3.0 x ULN if liver metastases present) * Aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT) \<= 3.0 x ULN (\<= 5.0 x ULN if liver metastases present). Note: ERCP or percutaneous stenting may be used to normalize the liver function tests. * Albumin \>= 1.5 9. LVEF by TTE or MUGA \>= 50% 10. Life expectancy \>= 12 weeks 11. Ability to give written informed consent according to local guidelines Exclusion Criteria: 1. Disease-Specific Exclusions 1. Prior full field radiotherapy \<= 4 weeks or limited field radiotherapy \<= 2 weeks prior to enrollment. Patients must have recovered from all therapy-related toxicities. The site of previous radiotherapy should have evidence of progressive disease if this is the only site of disease. 2. Prior biologic or immunotherapy \<= 2 weeks prior to registration. Patients must have recovered from all therapy-related toxicities 3. If history of other primary cancer, subject will be eligible only if she or he has: * Curatively resected non-melanomatous skin cancer * Curatively treated cervical carcinoma in situ * Other primary solid tumor curatively treated with no known active disease present and no treatment administered for the last 3 years 4. Concurrent use of other investigational agents and patients who have received investigational drugs \<= 4 weeks prior to enrollment. 2. General Medical Exclusions 1. Subjects known to have chronic or active hepatitis B or C infection with impaired hepatic function (ineligible if AST and ALT \> 3.0 x ULN). 2. History of any medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risks associated with study participation or study drug administration or may interfere with the conduct of the study or interpretation of study results 3. Male subject who is not willing to use adequate contraception upon enrollment into this study and for 6 months following the last dose of second-line treatment 4. Female subject (of childbearing potential, post-menopausal for less than 6 months, not surgically sterilized, or not abstinent) who is not willing to use an oral, patch or implanted contraceptive, double-barrier birth control, or an IUD during the course of the study and for 6 months following the last dose of second-line treatment 5. Female subject who is breast-feeding or who has positive serum pregnancy test 72 hours prior to randomization 6. Pleural effusion or ascites that causes respiratory compromise (\>= CTCAE grade 2 dyspnea) 7. Any of the following concurrent severe and/or uncontrolled medical conditions within 24 weeks of enrollment which could compromise participation in the study: * Unstable angina pectoris * Symptomatic congestive heart failure * Myocardial infarction \<= 6 months prior to registration and/or randomization * Serious uncontrolled cardiac arrhythmia * Uncontrolled diabetes * Active or uncontrolled infection * Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung * Chronic renal disease 8. Patients unwilling to or unable to comply with the protocol 9. Life expectancy of less than 12 weeks 10. Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored cancer study