A Phase II Study of Pertuzumab and Erlotinib for Metastatic or Unresectable Neuroendocrine Tumors
Condition: Neuroendocrine Tumors; Carcinoid Tumors; Adrenal Gland Tumors; Neuroblastoma; Pancreatic Neuroendocrine Tumors; Multiple Endocrine Neoplasia
MeSH terms: Neoplasms; Neuroblastoma; Neuroendocrine Tumors; Carcinoid Tumor; Endocrine Gland Neoplasms; Multiple Endocrine Neoplasia
Intervention: pertuzumab; erlotinib
Intervention description: 840 mg, 420 mg, iv; 150 mg, PO
Intervention MeSH terms: Erlotinib Hydrochloride; Pertuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: All
Healthy volunteers: No

Summary:

      To determine objective response rates (RR) by RECIST guideline version 1.1 for all patients
      treated with this strategy consisting of initial therapy with pertuzumab as a single agent
      and then addition of erlotinib for those who have stable disease or progressive disease at
      three months (Simon design).
    

Eligibility criteria:

        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