Clinical trials

The goal of this clinical trial is to test meal-timing as a novel and sustainable interventional approach during cancer treatment to improve therapeutic response, patient well-being and long-term metabolic health. In alignment with these priorities, we propose to focus on patients with histologically or cytologically confirmed solid tumors treated with curative-intent surgical resection and planned initiation of systemic adjuvant therapy (chemotherapy, targeted therapy, immunotherapy, and/or radiation per standard of care). A promising strategy for improving the efficacy of anticancer treatments and reducing associated toxicities involves combining treatment with fasting regimens. In pre-clinical and clinical studies, various forms of fasting have been shown to induce tumor regression and improve long-term survival. According to the differential stress sensitization theory, fasting is thought to sensitize tumor cells to the cytotoxic effects of chemotherapy and radiation, while protecting healthy cells by increasing stress resistance. While healthy cells slow their growth and become more stress resistant in response to fasting, cancer cells cannot survive in nutrient-deficient environments; although the underlying mechanisms are not fully understood. However, extended water-only fasting can be challenging for patients and poses undue health risks. Intermittent fasting, and specifically time-restricted eating (TRE), may offer a viable alternative. TRE involves eating within a shorter window (e.g., 8 hours) and fasting for the remainder of the day but involves no other dietary restrictions. Because of its simplicity, TRE may be more sustainable than other fasting regimens. TRE also improves several cardio-metabolic endpoints, including insulin sensitivity, which may also be beneficial during anticancer treatments.

This phase II trial compares the effects of immunoglobulin replacement therapy with a placebo for preventing infectious complications in patients receiving CD19 chimeric antigen receptor (CAR)-T cell therapy. Hypogammaglobulinemia is a common complication in patients who receive CD19 CAR-T cell therapy. This is a condition in which the level of immunoglobulins (antibodies) in the blood is low and the risk of infection is high. Immunoglobulin replacement therapy works by replacing the body's immunoglobulin G (IgG) antibodies with donor blood product derived IgG antibodies that may help prevent infection. IgG antibodies are often depleted as a result of CAR-T therapy. Giving immunoglobulin replacement therapy may prevent infectious complications in patients receiving CD19 CAR-T cell therapy.

This phase I trial tests the safety, side effects and best dose of decoy-resistant interleukin-18 (DR-18) and how well it works in treating patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) that has come back after a period of improvement (relapsed) or that remains despite treatment (persistent) after hematopoietic cell transplantation (HCT). HCT is the only curative therapy for most forms of AML and MDS. However, relapse occurs in a third of patients and is the most common cause of death after HCT. DR-18, a variant of the human cytokine interleukin-18, binds to IL-18 binding probein (IL-18BP) and overcomes the inhibitory effect of the IL-18BP on IL-18, which may boost the body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving DR-18 may be safe, tolerable and/or effective in treating patient with relapsed or persistent AML or MDS after HCT.

This phase I/II trial tests the safety and effectiveness of cell therapy (STEAP1 CART) with enzalutamide in treating patients with prostate cancer that continues to grow despite surgical or medical treatments to block androgen production (castration-resistant) and that has spread from where it first started (the prostate) to other places in the body (metastatic). Prostate cancer is the second leading cause of cancer deaths in men. Localized prostate cancer is often curable and even metastatic disease may respond to treatment for a few years. Despite multiple therapies, including hormone therapy and chemotherapy, metastatic castration-resistant prostate cancer (mCRPC) remains an incurable disease. Recently, adoptive cellular immunotherapies have been developed to transfer immunogenic cells to the patient to produce an anti-tumor response. Chimeric antigen receptor T (CART)-cell therapy is a type of treatment in which a patient's T-cells (a type of immune cell) are changed in the laboratory so they will attack tumor cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's tumor cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. Prostate stem cell antigen and prostate specific membrane antigen CAR T cell therapies have been shown to be safe and effective, but objective tumor responses remain rare. STEAP1 is an antigen that promotes cancer growth and spread and is found to be broadly expressed in mCRPC tissues. STEAP1 CART is CAR T cells that have been engineered with a STEAP1 antigen to better target prostate tumor cells. Enzalutamide is in a class of medications called androgen receptor inhibitors. It works by blocking the effects of androgen (a male reproductive hormone) to stop the growth and spread of cancer cells. Giving STEAP1 CART with enzalutamide may kill more tumor cells in patients with mCRPC.

This clinical trial tests a new mobile health application (app) called Planning Advance Care Together (PACT) to help people with cancer talk about and plan for advance care planning (the care they would want if they were unable to communicate) with their loved ones and doctors. The development of the PACT mobile app may help future patients incorporate their social network (typically, but not exclusively, family) into the advance care planning process.

This clinical trial studies how well exercise training works in improving immune activity and treatment tolerance and response in patients with non-small cell lung cancer (NSCLC) who are receiving immunotherapy. Immunotherapy may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread. The use of immunotherapy for the treatment of NSCLC has been rapidly increasing. Although immunotherapy have shown great potential in cancer therapy, not all patients benefit from this therapy and resistance to it can occur. This could be due to poor immune activity. It has been shown that exercise can enhance systemic immune activity in various ways. The exercise training used in this study is aerobic interval training. Aerobic interval training increases the heart rate and the body's use of oxygen and alternates short periods of intense aerobic exercise with less intense recovery periods. This may cause biological changes which may improve immune activity and treatment response in patients with NSCLC who are receiving immunotherapy.

The goal of this clinical trial is to test meal-timing as a novel and sustainable interventional approach during cancer treatment to improve therapeutic response and metabolic health in an understudied population. This clinical trial will enroll patients with rectal or breast cancer receiving neoadjuvant treatment at the Alaska Native Medical Center (ANMC), which is part of the Alaska Native Tribal Health Consortium (ANTHC). A promising strategy for improving the efficacy of anticancer treatments and reducing associated toxicities involves combining treatment with fasting regimens. In pre-clinical and clinical studies, various forms of fasting have been shown to induce tumor regression and improve long-term survival. According to the differential stress sensitization theory, fasting is thought to sensitize tumor cells to the cytotoxic effects of chemotherapy and radiation, while protecting healthy cells by increasing stress resistance. While healthy cells slow their growth and become more stress resistant in response to fasting, cancer cells cannot survive in nutrient-deficient environments; although the underlying mechanisms are not fully understood. However, extended water-only fasting can be challenging for patients and poses undue health risks. Intermittent fasting, and specifically time-restricted eating (TRE), may offer a viable alternative. TRE involves eating within a shorter window (e.g., 8 hours) and fasting for the remainder of the day but involves no other dietary restrictions. Because of its simplicity, TRE may be more sustainable than other fasting regimens. TRE also improves several cardio-metabolic endpoints, including insulin sensitivity, which may also be beneficial during anticancer treatments.

This phase Ib/II trial tests the safety, side effects, and best dose of quemliclustat in combination with enfortumab vedotin and pembrolizumab, and to see how well the combination works for the treatment of bladder, renal pelvis, or ureter urothelial cancer that cannot be removed by surgery (unresectable), that has spread to nearby tissue or lymph nodes (locally advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). Enfortumab vedotin is a monoclonal antibody, enfortumab, linked to an anticancer drug called vedotin. It works by helping the immune system to slow or stop the growth of cancer cells. Enfortumab attaches to a protein called nectin-4 on cancer cells in a targeted way and delivers vedotin to kill them. It is a type of antibody-drug conjugate. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Quemliclustat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving quemliclustat in combination with enfortumab vedotin and pembrolizumab and may be safe, tolerable and/or effective in treating patients with unresectable locally advanced and metastatic urothelial cancer.

This clinical trial evaluates the feasibility and effectiveness of a post-transplant dental cleaning for the prevention of chronic graft versus host disease (GVHD) in patients undergoing an allogeneic hematopoietic cell transplant (HCT). HCT is the only curative treatment for some types of blood cancer. Unfortunately, this approach can lead to the development of GVHD, which is a disease caused when cells from a donated stem cell graft attack the normal tissue of the transplant patient. Some research has shown that the bacteria that is present in the dental plaque soon after transplant may affect the development of chronic GVHD. Dental cleanings prior to transplant are part of the normal standard of care for patients undergoing HCT. Adding an additional cleaning shortly after HCT may be effective for preventing the development of chronic GVHD.

Tobacco use is the leading cause of preventable cancer deaths. Among young adults, approximately 1 in 5 use commercial nicotine and tobacco products, putting them at risk of developing nicotine addiction and long-term health effects from exposure to toxicants. Innovative approaches are needed to engage young adults in treatment, as they are less engaged in traditional treatment. This clinical trial compares two versions of a mobile health intervention called Living Free from Tobacco (LiFT), designed to support nicotine and tobacco cessation among young adults. Both versions of the app are designed to motivate and support young adults to stop using nicotine and tobacco, regardless of current readiness to quit. Version A of the LiFT app (LiFT A) focuses on increasing psychological flexibility to support cessation, while Version B (LiFT B) provides educational content and resources related to tobacco use and cessation. Both versions of the program are delivered through a smartphone application and include accompanying text messages.

This clinical trial evaluates a smartphone application (app) called Acceptance and Commitment Therapy (ACT) on Vaping for helping young adults quit using electronic cigarettes (e-cigarettes). E-cigarettes pose numerous risks, particularly to youth and young adults. Addressing the high prevalence of e-cigarette use by young adults requires effective and accessible treatments to support current users to quit. Research shows this group prefers and benefits from newer methods of treatment delivery such as digital interventions. ACT on Vaping is a digital therapeutic intended to deliver behavioral therapy to young adults who vape to motivate and support abstinence from all nicotine and tobacco products. The app contains sessions that promote awareness of cues that trigger tobacco use and teach skills for responding to these triggers in a way that is tailored for the participant's readiness to quit. Receiving access to the ACT on Vaping app may be effective in helping young adults quit vaping.

This clinical trial studies whether an intervention that addresses two or more levels of care (multilevel intervention) increases follow-up of abnormal, non-invasive, colorectal cancer (CRC) screening test results. The fecal immunochemical test (FIT) is a non-invasive, stool-based, CRC screening test. FITs are relatively inexpensive and can be completed at home, for these reasons, it is a preferred method of CRC screening in healthcare settings that care for under-resourced patients or have limited colonoscopy access. For FIT-based CRC screening to be effective, abnormal results must be followed by a colonoscopy, however many patients fail to complete this recommended follow-up test. The multilevel intervention addresses barriers to follow-up colonoscopy at the patient and health system levels of care through a CRC screening patient navigator, an educational video, and transportation assistance. The navigator provides patient support and assistance with colonoscopy scheduling. The educational video addresses identified patient fears around colonoscopies. Transportation assistance is offered after the colonoscopy through a rideshare program to address transportation barriers. Therefore, this multilevel intervention may increase follow-up colonoscopy completion in patients with abnormal FIT results.

This phase I/II trial studies the side effects and best dose of 211\^astatine(At)-BC8-B10 before donor stem cell transplant in treating patients with high-risk acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or mixed-phenotype acute leukemia. Radioactive substances, such as astatine-211, linked to monoclonal antibodies, such as BC8, can bind to cancer cells and give off radiation which may help kill cancer cells and have less of an effect on healthy cells before donor stem cell transplant.

This phase I/II trial studies the side effects and best dose of a radioactive agent linked to an antibody (211At-BC8-B10) followed by donor stem cell transplant in treating patients with high-risk acute leukemia or myelodysplastic syndrome that has come back (recurrent) or isn't responding to treatment (refractory). 211At-BC8-B10 is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Giving chemotherapy and total body irradiation before a stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the patient, they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can attack the body's normal cells, called graft versus host disease. Giving cyclophosphamide, mycophenolate mofetil, and tacrolimus after a transplant may stop this from happening.

This phase II trial investigates how well a naive T cell depleted graft work for the reduction of graft versus host disease in patients with non-malignant diseases requiring hematopoietic cell transplantation. Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient, they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. The donated stem cells may also replace the patient's immune cells and help destroy any remaining cancer cells.

This clinical trial evaluates remotely delivered, community-aligned weight loss interventions in Latina breast cancer survivors. Breast cancer is the second leading cause of cancer death among women in the US. There are population differences in breast cancer mortality, based on specific risk factors, including obesity. Cancer is the leading cause of death among Latinos, and among Latinas, breast cancer is the leading cause of cancer death. An estimated 80% of Latinas in the United States have overweight/obesity, which is associated with poorer breast cancer outcomes. However, few, if any, effective interventions exist to promote and maintain weight loss in Latina breast cancer survivors. The development of an adaptive program that provides survivors with the support they need, as opposed to what is typically available, to improve breast cancer survivorship.

This clinical trial tests an adapted version of the Helping Ovarian Cancer Patients Cope (HOPE) intervention to address burnout among gynecologic oncology clinicians. Stress and burnout among gynecologic oncology clinicians can have far-reaching impacts not only on physicians at the individual level (e.g., distress, mental illness) but also at the professional (e.g., worse patient outcomes, increased errors) and societal levels (fewer physicians in this specialty, more system strain). The original Helping Ovarian Cancer Patients Cope (HOPE) is a workshop to promote hope among patients with ovarian cancer through creating positive narratives using the hope theory and social-cognitive theory. The adapted intervention for clinicals (HOPE-C) will use the same concepts but tailored to clinician experiences by fostering peer support and retelling their challenging stories and may address burnout for gynecologic oncology clinicians.

The purpose of this study is to determine whether high-intensity exercise and high-fiber diet are feasible and improve various health outcomes among participants with advanced melanoma receiving immunotherapy. The names of the groups in this research study are: * High-Intensity Exercise (EX) * High-fiber Diet (DT) * Combined High-Intensity Exercise and High-Fiber Diet (COMB) * Attention Control (AC)

This phase I trial studies the side effects and best dose of autologous CD8+ and CD4+ transgenic T cells expressing high affinity KRASG12V mutation-specific T cell receptors (FH-A11KRASG12V-TCR) and to see how well they work in treating patients with solid tumor cancers that has spread from where it first started (primary site) to other places in the body (metastatic). T cells are infection fighting blood cells that can kill tumor cells. The T cells given in this study will come from the patient and will have a new gene put in them that makes them able to recognize KRAS G12V, a protein on the surface of tumor cells. These KRAS G12V-specific T cells may help the body's immune system identify and kill KRAS G12V solid cancer tumor cells.

This phase I/II trial studies the best dose of total body irradiation with astatine-211 BC8-B10 monoclonal antibody for the treatment of patients with nonmalignant diseases undergoing hematopoietic cell transplant. Radiation therapy uses high energy gamma rays to kill cancer cells and shrink tumors. Astatine-211-labeled BC8-B10 monoclonal antibody is a monoclonal antibody, called anti-CD45 monoclonal antibody BC8-B10, linked to a radioactive/toxic agent called astatine 211. Anti-CD45 monoclonal antibody BC8-B10 is attached to CD45 antigen positive cancer cells in a targeted way and delivers astatine 211 to kill them. Giving astatine-211 BC8-B10 monoclonal antibody and total-body irradiation before a donor stem cell transplant may help stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells.

This clinical trial develops and studies whether a restorative justice-based lung cancer screening (LCS) decision-making support intervention tailored for Black individuals increases LCS among Black community members. Lung cancer remains the leading cause of cancer deaths among Black men and women. LCS with yearly low-dose chest computed tomography (CT) is recommended for people with current or recent tobacco use (within 15 years) who are aged 50-80 with at least a 20 pack-year smoking history. LCS lowers lung cancer death by 20%; however, data shows that LCS completion remains low among minority groups in the United States. The restorative justice-based LCS decision-making support intervention in this trial has been specifically tailored to meet the needs of Black individuals. It is designed to reduce racial unfairness by promoting trust, shared understanding, and empowerment in clinical decision making while addressing the social and historical circumstances of health inequalities. This may be an effective way to increase LCS among Black community members.

This clinical trial studies whether less fit adults with acute myeloid leukemia (AML) or myeloid neoplasms are willing to let a computer program decide (randomization) whether they receive lower- or higher-intensity chemotherapy. Historically, treatment decision-making for patients with AML or myeloid neoplasms has divided patients into two categories, with patients considered fit receiving intensive "curative" chemotherapy, and patients considered unfit, such as older patients with a higher risk of early death from therapy, receiving non-intensive "palliative" therapy or no therapy. With the introduction of new treatment agents, it has become difficult to determine the difference between intensive and non-intensive therapy, especially for patients considered unfit for whom treatment-related side effects remain a concern. Treatment intensity is best identified through randomized trials but often patients are unwilling to undergo randomization due to preset beliefs. However, with improved supportive care and the awareness that new treatment agents may have similar risks as intensive therapy, it may be possible that more patients are willing to be randomized. This may help identify the best treatment intensity for less fit adults with AML or myeloid neoplasms, which may improve outcomes.

Cervical cancer disproportionately affects women in low- and middle-income countries (LMICs), particularly women living with HIV (WLWH) who have a 6-fold increased risk of cervical cancer compared to women in the general population. Thermal ablation (TA) is recommended by the World Health Organization (WHO) to treat cervical precancerous lesions, although its efficacy can be suboptimal in WLWH. The proposed study will evaluate the feasibility, acceptability, and safety of a two-probe TA technique (endocervical and ectocervical probes) and whether this approach improves treatment outcomes among WLWH compared to one (ectocervical) probe. This innovation has the potential to significantly enhance cervical cancer prevention efforts in high-burden settings. It will also contribute towards achieving the 90-70-90 goals of the WHO strategy for accelerated elimination of cervical cancer as a public health problem by 2030.

Cervical cancer disproportionately affects women in low- and middle-income countries (LMICs), particularly women living with HIV (WLWH) who have a 6-fold increased risk of cervical cancer compared to women in the general population. While thermal ablation (TA) is a WHO- recommended treatment for cervical precancerous lesions, its efficacy can be suboptimal in WLWH. We will also conduct a feasibility treatment cohort study of up to 300 Zimbabwean WLWH to provide evidence for a larger treatment effectiveness study. The proposed study will evaluate the feasibility, acceptability, and safety of a two-probe TA technique (endocervical and ectocervical probes) and whether this approach improves treatment outcomes among WLWH compared to one (ectocervical) probe. This innovation has the potential to significantly enhance cervical cancer prevention efforts in high-burden settings and to contribute towards achieving the 90-70-90 goals of the World Health Organization's (WHO) strategy for accelerated elimination of cervical cancer as a public health problem by 2030.

This phase I trial tests the safety, side effects and best dose of FH-WT1-E50 TCR T cells with azacitidine for the treatment of minimal residual disease (MRD) positive acute myeloid leukemia (AML). T cells are infection fighting blood cells that can kill tumor cells. The T cells given in this study will come from the patient and will have a new gene put in them that makes them able to recognize WT1, a protein on the surface of cancer cells. These WT1-specific T cells may help the body's immune system identify and kill WT1 cancer cells. Azacitidine is in a class of medications called antimetabolites. It works by stopping or slowing the growth of cancer cells. Giving FH-WT1-E50 TCR T Cells with azacitidine may be safe and/or effective for the treatment of MRD positive AML.