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.

Patients will be registered prior to, during or at the completion of neoadjuvant chemotherapy
(Paclitaxel 175 mg/m2 IV over 3 hours and Carboplatin AUC 6 IV on Day 1 every 21 days for 3-4
cycles). Registered patients who progress during neoadjuvant chemotherapy will not be
eligible for iCRS and will be removed from the study.

Following completion of neoadjuvant chemotherapy, interval cytoreductive surgery (iCRS) will
be performed in the usual fashion in both arms. Patients will be randomized at the time of
iCRS (iCRS must achieve no gross residual disease or no disease >1.0 cm in largest diameter)
to receive HIPEC or no HIPEC. Patients randomized to HIPEC (Arm A) will receive a single dose
of cisplatin (100mg/m2 IP over 90 minutes at 42 C) as HIPEC. After postoperative recovery
patients will receive standard post-operative platinum-based combination chemotherapy.
Patients randomized to surgery only (Arm B) will receive postoperative standard chemotherapy
after recovery from surgery.

Both groups will receive an additional 2-3 cycles of platinum-based combination chemotherapy
per institutional standard (Paclitaxel 175 mg/m2 IV over 3 hours and Carboplatin AUC 6 IV on
Day 1 every 21 days for 2-3 cycles) for a maximum total of 6 cycles of chemotherapy
(neoadjuvant plus post-operative cycles) followed by niraparib individualized dosing until
progression or 36 months (if no evidence of disease).

This phase II/III trial compares the addition of nivolumab to the usual treatment of paclitaxel and ramucirumab to paclitaxel and ramucirumab alone in treating patients with gastric or esophageal adenocarcinoma that that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Ramucirumab is a monoclonal antibody that may prevent the growth of new blood vessels that tumors need to grow. Paclitaxel is in a class of medications called antimicrotubule agents. It stops cancer cells from growing and dividing and may kill them. Adding nivolumab to ramucirumab and paclitaxel may work better to treat patients with advanced stomach or esophageal cancer.

The primary objective of this phase IIb/III study is to evaluate whether the combination of
lurbinectedin plus doxorubicin given as first line treatment for metastatic leiomyosarcoma
(LMS) prolongs the progression-free survival (PFS) by Independent Review Committee (IRC) when
compared to doxorubicin administered as a single agent.

This phase III trial tests two hypotheses in patients with low-risk and average-risk medulloblastoma. Medulloblastoma is a type of cancer that occurs in the back of the brain. The term, risk, refers to the chance of the cancer coming back after treatment. Subjects with low-risk medulloblastoma typically have a lower chance of the cancer coming back than subjects with average-risk medulloblastoma. Although treatment for newly diagnosed average-risk and low-risk medulloblastoma is generally effective at treating the cancer, there are still concerns about the side effects of such treatment. Side effects or unintended health conditions that arise due to treatment include learning difficulties, hearing loss or other issues in performing daily activities. Standard therapy for newly diagnosed average-risk or low-risk medulloblastoma includes surgery, radiation therapy, and chemotherapy (including cisplatin). Cisplatin may cause hearing loss as a side effect. In the average-risk medulloblastoma patients, this trial tests whether the addition of sodium thiosulfate (STS) to standard of care chemotherapy and radiation therapy reduces hearing loss. Previous studies with STS have shown that it may help reduce or prevent hearing loss caused by cisplatin. In the low-risk medulloblastoma patients, the study tests whether a less intense therapy (reduced radiation) can provide the same benefits as the more intense therapy. The less intense therapy may cause fewer side effects. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of cancer cells. The overall goals of this study are to see if giving STS along with standard treatment (radiation therapy and chemotherapy) will reduce hearing loss in medulloblastoma patients and to compare the overall outcome of patients with medulloblastoma treated with STS to patients treated without STS on a previous study in order to make sure that survival and recurrence of tumor is not worsened.

This phase II trial studies how well inotuzumab ozogamicin works in treating younger patients with B-lymphoblastic lymphoma or CD22 positive B acute lymphoblastic leukemia that has come back (relapsed) or does not respond to treatment (refractory). Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a toxic agent called ozogamicin. Inotuzumab attaches to CD22 positive cancer cells in a targeted way and delivers ozogamicin to kill them.

This phase II trial tests how well neratinib prior to the primary treatment (neoadjuvant) works in treating patients with stage I-III HER2 mutated lobular breast cancers. Neratinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the spread of cancer cells. Giving neratinib in addition to normal therapy may work better in treating cancer than the endocrine therapy patients would normally receive.

This phase I/II trial studies the side effects and best dose of M3814 and to see how well it works when given together with radiation therapy in treating patients with pancreatic cancer that cannot be removed by surgery and has not spread to other parts of the body (localized). M3814 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Giving M3814 and hypofractionated radiation therapy together may work better than radiation therapy alone in the treatment of patients with localized pancreatic cancer.

This pilot trial compares drug exposure levels using a new method for dosing vincristine in infants and young children compared to the standard dosing method based on body surface area (BSA) in older children. Vincristine is an anticancer drug used to a variety of childhood cancers. The doses anticancer drugs in children must be adjusted based on the size of the child because children vary significantly in size (height, weight, and BSA) and ability to metabolize drugs from infancy to adolescence. The dose of most anticancer drugs is adjusted to BSA, which is calculated from a patients weight and height. However, infants and young children have more severe side effects if the BSA is used to calculate their dose, so new dosing models have to be made to safely give anticancer drugs to the youngest patients. This new method uses a BSA-banded approach to determine the dose. Collecting blood samples before and after a dose of the drug will help researchers determine whether this new vincristine dosing method results in equivalent drug levels in the blood over time in infants and young children compared to older children.

This phase II trial studies the effect of panitumumab-IRDye800 in detecting head and neck cancer during surgery in patients head and neck cancer. Doctors who perform surgery for head and neck cancer are well-trained in removing all of the cancer that can be seen during the operation; however, there are times when there is cancer that is so small that it cannot be seen by the surgeon. Panitumumab-IRDye800 is a combination of panitumumab and IRDye800CW. Panitumumab works by attaching to the cancer cell in a unique way that allows the drug to get into the cancer tissue. IRDye800CW is an investigational dye that, when tested in the laboratory, helps various characteristics of human tissue show up better when using a special camera. Panitumumab-IRDye800 is a combination of the drug and the dye that attaches to cancer cells and appears to make them visible to the doctor when he or she uses the special camera during the surgery. Giving panitumumab-IRDye800 may help doctors better identify cancer in the operating room.