Clinical Trials Search at Vanderbilt-Ingram Cancer Center

This is an umbrella study evaluating the efficacy and safety of multiple treatment
combinations in participants with metastatic or inoperable locally advanced breast cancer.

The study will be performed in two stages. During Stage 1, four cohorts will be enrolled in
parallel in this study:

Cohort 1 will consist of Programmed death-ligand 1 (PD-L1)-positive participants who have
received no prior systemic therapy for metastatic or inoperable locally advanced
triple-negative breast cancer (TNBC) (first-line [1L] PD-L1+ cohort).

Cohort 2 will consist of participants who had disease progression during or following 1L
treatment with chemotherapy for metastatic or inoperable locally-advanced TNBC and have not
received cancer immunotherapy (CIT) (second-line [2L] CIT-naive cohort).

Cohort 3 will consist of participants with locally-advanced or metastatic HR+, HER2-negative
disease with PIK3CA mutation who may or may not have had disease progression during or
following previous lines of treatment for metastatic disease (HR+cohort).

Cohort 4 will consist of participants with locally-advanced or metastatic HER2+ /HER2-low
disease with PIK3CA mutation who had disease progression on standard-of-care therapies (HER2+
/HER2-low cohort).

In each cohort, eligible participants will initially be assigned to one of several treatment
arms (Stage 1). In addition, participants in the 2L CIT-nave cohort who experience disease
progression, loss of clinical benefit, or unacceptable toxicity during Stage 1 may be
eligible to continue treatment with a different treatment combination (Stage 2), provided
Stage 2 is open for enrollment.

This phase III trial tests how well adding dinutuximab to induction chemotherapy along with standard of care surgery radiation and stem cell transplantation works for treating children with newly diagnosed high risk neuroblastoma. Dinutuximab is a monoclonal antibody that binds to a molecule called GD2, which is found in greater than normal amounts on some types of cancer cells. This helps cells of the immune system kill the cancer cells. Chemotherapy drugs such as cyclophosphamide, topotecan, cisplatin, etoposide, vincristine, dexrazoxane, doxorubicin, temozolomide, irinotecan and isotretinoin, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing or by stopping them from spreading. During induction, chemotherapy and surgery are used to kill and remove as much tumor as possible. During consolidation, very high doses of chemotherapy are given to kill any remaining cancer cells. This chemotherapy also destroys healthy bone marrow, where blood cells are made. A stem cell transplant is a procedure that helps the body make new healthy blood cells to replace the blood cells that may have been harmed by the cancer and/or chemotherapy. Radiation therapy is also given to the site where the cancer originated (primary site) and to any other areas that are still active at the end of induction.