Protocol: SWOG – S2012

Schema – S2012

Please Note: Below is partial eligibility, for full eligible requirement’s, please contact GHCI Research Department at (810) 762-8181, (810) 762-8079 and/or (810) 762-8038. Thank  you!

Eligibility:

1. Participants must have histologically-confirmed (local site pathological confirmation sufficient) extrapulmonary poorly differentiated, small cell neuroendocrine carcinoma that is metastatic.
2. Participants must have radiologically evaluable disease, measurable or nonmeasurable, per RECIST 1.1 criteria. All measurable and non-measurable lesions
   must be assessed by CT scan within 28 days prior to registration. For patients who received one cycle of platinum + etoposide prior to registration, at least 21
   days must have elapsed between Day 1 of platinum + etoposide and the preregistration CT scan.
3. Participants must have brain MRI (or CT head with contrast if there is contraindication to MRI brain) within 28 days prior to registration.
4. Participants must not have symptomatic central nervous system (CNS) metastases.
5. Participants must not have known or suspected leptomeningeal disease.
6. Participants must not have small cell NEC mixed with urothelial carcinomas.
7. Participants with prior history of non-metastatic (localized/locally advanced disease) extrapulmonary poorly differentiated small cell NEC may have had prior platinum-based therapy ± radiation ± surgery provided that all therapy was completed ≥ 6 months prior to registration.
8. Participants must discontinue denosumab prior to study registration and plan to replace with a bisphosphonate while on the study.
9. Participants must not have had prior treatment for metastatic disease EXCEPT one cycle of platinum (carboplatin/cisplatin) + etoposide is allowed prior to
   registration. Other chemotherapy regimens are not allowed.
10. Participants must not have had prior treatment with an anti-PD-1, anti-PD-L1, antiPD-L2, CD137 agonists, anti-CTLA-4 agent, or any other immune checkpoint
    inhibitors for any neuroendocrine neoplasm. Immune checkpoint inhibitors given for other cancer indications are allowed provided last therapy was given at least
    12 months prior to study registration.
11. Participants must not have received treatment with systemic immunostimulatory agents including, but not limited to, interferon and interleukin2 [IL-2] within 4 weeks
    or 5 half-lives of the drug (whichever is longer) prior to registration.
12. Participants must be ≥ 18 years of age.
13. Zubrod Performance Status of ≤ 2.

Protocol – Alliance – A021804

Schema – A021804

Please Note – Below is partial eligibility, for full eligibility requirement’s, please contact GHCI Research Department at (810) 762-8181, (810) 762-8079 and/or (810) 762-8038. Thank you!

Eligibility:

1. Histologically-proven advanced (metastatic or unresectable primary) pheochromocytoma or paraganglioma.
2. Advanced (metastatic or unresectable primary) disease.
3. Histologically-proven pheochromocytoma or paraganglioma.
4. Radiographic evidence of disease progression by RECIST v1.1 criteria in the 12 months prior to registration.
5. Measurable disease.
6. Prior treatment with other chemotherapy, radiotherapy (including peptide radionuclide receptor therapy [PRRT]), or surgery must be completed ≥ 28 days prior to registration. Patients must have recovered from any effects of any major surgery prior to registration.  Prior treatment with radiolabeled MIBG must be completed ≥ 12 weeks prior to registration and lifetime cumulative 131I-MIBG dose must be < 1000 MBq kg-1 (36 mCi kg-1).  No prior treatment with temozolomide, dacarbazine, or a poly ADP ribose polymerase (PARP) inhibitor.
7. Must me at least 18 years of age.
8. ECOG Performance Status 0-2.
9. Concurrent use of combination antiretroviral therapy (ART) is not permitted.

Protocol: Alliance – A021602

Schema – A021602

Please Note: Below is partial eligibility, for full eligibility requirements, please contact GHCI Research Department at (810) 762-8181, (810) 762-8079 and/or (810) 762-8038. Thank you!

Eligibility:

1. Well- or moderately-differentiated neuroendocrine tumors of pancreatic and non-pancreatic (i.e. carcinoid) origin by local pathology.  The pathology report must state ONE of the following: 1) well- or moderatelydifferentiated neuroendocrine tumor, 2) low- or intermediate-grade neuroendocrine tumor, or 3) carcinoid tumor or atypical carcinoid tumor. Documentation of histology from a primary or metastatic site is allowed.  Patients with poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid tumor, or goblet cell carcinoid tumor are not eligible.
2. Locally advanced/unresectable or metastatic disease.
3. Histological documentation of neuroendocrine tumor of pancreatic, gastrointestinal (GI), lung, thymus, other, or unknown primary site. GI, lung, thymus, other, and unknown primary NETs will enroll in the carcinoid tumor cohort of the study. Functional (associated with a clinical hormone syndrome) or nonfunctional tumors are allowed.
4. Patients must have measurable disease.  Lesions must be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 1 cm with CT or MRI (or ≥ 1.5 cm for lymph nodes). Non-measurable disease includes disease smaller than these dimensions or lesions considered truly nonmeasurable including: leptomeningeal disease, ascites, pleural or pericardial effusion, lymphangitic involvement of skin or lung.
5. Patient must have experienced disease progression on or intolerance leading to treatment discontinuation of at least one FDA-approved line of therapy (except somatostatin analogs). Prior lines of therapy may include: everolimus, sunitinib, or lutetium Lu 177 dotatate in patients with pancreatic NET; everolimus in patients with lung NET; everolimus or lutetium Lu 177 dotatate in patients with gastrointestinal NET.
6. Prior treatment (except somatostatin analogs) with biologic therapy, immunotherapy, chemotherapy, investigational agent for malignancy, and/or radiation must be completed at least 28 days prior to registration.
7. Prior treatment with somatostatin analogs is allowed, and continuation of treatment with somatostatin analogs while on cabozantinib/placebo is allowed provided that the patient has been on a stable dose for at least two months.
8. Prior treatment with cabozantinib is not allowed.
9. No “currently active” second malignancy other than non-melanoma skin cancers or cervical carcinoma in situ. Patients are not considered to have a “currently active” malignancy if they have completed therapy and are free of disease for ≥ 3 years.
10. Other planned concurrent investigational agents or other tumor directed therapies (chemotherapy, radiation) are not allowed while on this study.
11. Must be at least 18 years of age.
12. ECOG Performance Status 0-2.