Tokyo%20shibuya-ku, Japan

Safety and Preliminary Effectiveness of BNT327, an Investigational Therapy for Breast Cancer, When Given in Combination With Chemotherapy

Participants will be treated until disease progression, intolerable toxicity, participant withdrawal, death, study termination or up to 2 years (whichever occurs first). The study plans to randomize or assign eligible participants into two cohorts, i.e., Cohort 1 and Cohort 2. In Cohort 1, participants will be randomized to two treatment arms investigating two dose levels of BNT327 in combination with Nab-paclitaxel. Cohort 2 will not begin until the appropriate dose to move forward has been determined from Cohort 1. After this, the arms in Cohort 2 exploring different chemotherapy combinations will begin to enroll. Participants in Cohort 2, Arm 1 will receive the optimal dose of BNT327 in combination with paclitaxel. Participants in Cohort 2, Arms 2 and 3, will receive the equivalent dose of BNT327 administered once every 3 weeks (Q3W) in combination with gemcitabine plus carboplatin (Arm 2), or eribulin (Arm 3).

Testing Olaparib for One or Two Years, With or Without Bevacizumab, to Treat Ovarian Cancer

PRIMARY OBJECTIVE: I. To determine investigator assessed progression-free survival using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 (non-inferiority) for one versus (vs.) two years of maintenance olaparib. SECONDARY OBJECTIVES: I. To evaluate overall survival (OS360) in the modified intent to treat (ITT) population, with time at risk for progression/death starting 360 days after randomization. II. To evaluate progression-free survival (PFS), PFS2 and overall survival (OS) in the ITT population. III. To evaluate PFS, PFS2, and OS in the as-treated population. IV. To evaluate toxicity, including rates of myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), and other secondary malignancies, in the safety population. EXPLORATORY OBJECTIVE: I. To evaluate the moderating effect of physician-choice bevacizumab (as stratified) on randomized treatment effect estimates. TRANSLATIONAL OBJECTIVES: I. To assess BRCA reversion mutations in circulating tumor deoxyribonucleic acid (ctDNA) as a predictor of poor response in the BRCA mutated (BRCAm) population. II. To correlate a combined assay assessing quantitative BRCA1 and RAD51C promoter methylation and pathogenic variants in core homologous recombination repair (HRR) genes with clinical homologous recombination deficiency (HRD) testing and outcomes in the BRCA wildtype (BRCAwt) population. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I (REFERENCE): Patients receive olaparib orally (PO) twice daily (BID) on days 1-21 of each cycle. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients may also receive bevacizumab IV on day 1 of each cycle. Cycles of bevacizumab repeat every 21 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and computed tomography (CT) and/or magnetic resonance imaging (MRI) throughout the study. ARM II (EXPERIMENTAL): Patients receive olaparib PO BID on days 1-21 of each cycle. Cycles repeat every 21 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients may also receive bevacizumab IV on day 1 of each cycle. Cycles of bevacizumab repeat every 21 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and CT and/or MRI throughout the study. After completion of study treatment, patients are followed up every 3 months for 2 years, then every 6 months for 3 years.

Study of Targeted Therapy vs. Chemotherapy in Patients With Thyroid Cancer

PRIMARY OBJECTIVE: I. To compare progression-free survival (PFS) in patients with BRAF V600Em differentiated thyroid cancer who progressed on frontline multikinase inhibitor treated with dabrafenib/trametinib or cabozantinib. SECONDARY OBJECTIVES: I. To compare the objective response rate in patients with BRAF V600Em differentiated thyroid cancer that progressed on frontline multikinase inhibitor treated with dabrafenib/trametinib or cabozantinib. II. To compare the duration of response in patients with BRAF V600Em differentiated thyroid cancer that progressed on frontline multikinase inhibitor treated with dabrafenib/trametinib or cabozantinib. III. To compare the overall survival in patients with BRAF V600Em differentiated thyroid cancer that progressed on frontline multikinase inhibitor treated with dabrafenib/trametinib or cabozantinib. IV. To compare the PFS2 in patients with BRAF V600Em differentiated thyroid cancer that progressed on frontline multikinase inhibitor treated with dabrafenib/trametinib or cabozantinib. V. To compare the safety/tolerability in patients with BRAF V600Em differentiated thyroid cancer that progressed on frontline multikinase inhibitor treated with dabrafenib/trametinib or cabozantinib. QUALITY OF LIFE OBJECTIVE: I. To assess patient tolerability of treatment using the Functional Assessment Cancer Therapy General (FACT G)P5 and general quality of life using the FACT-G7. OUTLINE: Patients are randomized to 1 of 2 arms. Patients may crossover to other treatment arm at the time of progression. ARM A: Patients receive dabrafenib orally (PO) twice per day (BID) and trametinib PO once per day (QD) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) scan, blood sample collection and may undergo magnetic resonance imaging (MRI) throughout the study. ARM B: Patients receive cabozantinib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, blood sample collection and may undergo MRI throughout the study. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months thereafter up to 5 years.

Testing Whether the Addition of Carboplatin Chemotherapy to Cabazitaxel Chemotherapy Will Improve Outcomes Compared to Cabazitaxel Alone in People With Castrate-Resistant Prostate Cancer That Has Spread Beyond the Prostate to Other Parts of the Body

PRIMARY OBJECTIVES: I. To compare radiographic progression free survival (rPFS) between the two treatment arms in the subset of aggressive variant prostate cancer - molecular-pathologic signature (AVPC-MS)-positive participants. II. If the AVPC-MS positive test is statistically significant, test in AVPC-MS negative participants whether the combination of carboplatin and cabazitaxel improves rPFS. SECONDARY OBJECTIVES: I. To compare overall survival (OS) between the two treatment arms, stratified by AVPC-MS positive versus (vs.) negative. II. To compare response rates for prostate specific antigen (PSA), total alkaline phosphatase, and Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 between the two treatment arms, stratified by AVPC-MS positive vs. negative. III. To compare rPFS between the two treatment arms for the full trial. IV. To compare rPFS between the two treatment arms for the AVPC-MS negative group in the absence of a positive treatment effect in the AVPC-MS positive group. V. To compare progression free survival (PFS) between the two treatment arms, stratified by AVPC-MS positive vs. negative. VI. To compare toxicities between the two arms in participants who receive any treatment on study. BANKING OBJECTIVES: I. To bank specimens for future correlative studies. OUTLINE: Patients are randomized to 1 of 2 arms. ARM 1: Patients receive cabazitaxel intravenously (IV) over 60 minutes on day 1 of each cycle and prednisone orally (PO) twice daily (BID) on days 1-21 of each cycle. Cycles repeat every 21 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity. ARM 2: Patients receive cabazitaxel and carboplatin IV over 60 minutes on day 1 of each cycle and prednisone PO BID on days 1-21 of each cycle. Cycles repeat every 21 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity. All patients undergo blood sample collection, bone scan, computed tomography (CT), positron emission tomography (PET), or magnetic resonance imaging (MRI) throughout the trial and chest radiography (x-ray) before randomization. After completion of study treatment, patients are followed every 12 weeks for 1 year after randomization, and then every 26 weeks for up to 4 years after randomization or until death, whichever occurs first.

Cost Communication and Financial Navigation in Cancer Patients (COSTCOM)

PRIMARY OBJECTIVE: I. To compare patient-reported cost-related cancer care non-adherence at 12 months after completion of baseline survey between the enhanced usual care (EUC) and CostCOM study arms. SECONDARY OBJECTIVES: I. To compare patient-reported material financial hardship at 12 months after completion of baseline survey between the EUC and CostCOM study arms. II. To compare patient-reported financial worry at 12 months after completion of baseline survey between the EUC and CostCOM study arms. III. To compare patient-reported quality of life at 12 months after completion of baseline survey between the EUC and CostCOM study arms. IV. To compare patient satisfaction with care at 12 months after completion of baseline survey between the EUC and CostCOM study arms. EXPLORATORY OBJECTIVES: I. To describe CostCOM (Arm B) patients and their provider experience with various implementation outcomes. II. To assess accuracy of out-of-pocket estimates communicated with the CostCOM (Arm B) patients at part of the intervention with their reported actual out-of-pocket cost. III. To compare neighborhood characteristics of patient participants versus (vs.) practice patient population. IV. To assess patients' satisfaction with CostCOM in patients with Arm B. V. To assess patients' receipt of financial navigation via internal practice or external resources. VI. To evaluate longitudinal changes in cost-related cancer care non-adherence, material hardship, financial worry, quality of life and satisfaction with care. OUTLINE: Non-patient participants: Participants complete surveys and participant in 1 on 1 in depth semi-structured interview over 20-30 minutes at 15-39 months after first patient enrollment. Patients are randomized to 1 of 2 arms. ARM A: Patients receive Patient Advocate Foundation (PAF) brochure describing financial navigation services. ARM B: Patients receive usual financial care per practice standard of care and CostCOM financial counseling sessions over 1 hour within 30 days after enrollment and at 3, 6 and 12 months. Patients are followed up within 12 months of study intervention completion.

Mobile Health for Adherence in Breast Cancer Patients

PRIMARY OBJECTIVE: I. To compare CDK4/6 inhibitors (CDK4/6i) adherence at 12 months after completion of the baseline survey captured using electronic monitoring between the EUC (Arm A) and CONCURxP (Arm B) arms. SECONDARY OBJECTIVES: I. To compare CDK4/6i adherence at 12 months after completion of the baseline survey captured through self-report between the EUC (Arm A) and CONCURxP (Arm B) arms. II. To compare CDK4/6i persistence at 12 months after completion of the baseline survey captured using electronic monitoring between the EUC (Arm A) and CONCURxP (Arm B) arms. III. To compare symptom burden at 12 months between the EUC (Arm A) and CONCURxP (Arm B) arms. IV. To compare quality of life at 12 months between the EUC (Arm A) and CONCURxP (Arm B) arms. V. To compare patient-provider communication at 12 months between the EUC (Arm A) and CONCURxP (Arm B) arms. VI. To compare self-efficacy for managing symptoms at 12 months between the EUC (Arm A) and CONCURxP (Arm B) arms. VII. To compare financial worry at 12 months between the EUC (Arm A) and CONCURxP (Arm B) arms. EXPLORATORY OBJECTIVES: I. To assess longitudinal changes of patient-reported outcomes (self reported adherence, symptom burden, quality of life, and financial worry) from the EUC (Arm A) and CONCURxP (Arm B) arms. II. To compare healthcare utilization at 12 months between the EUC (Arm A) and CONCURxP (Arm B) arms. III. To compare progression-free survival at 12 months between the EUC (Arm A) and CONCURxP (Arm B) arms. IV. To compare overall survival at 12 months between the EUC (Arm A) and CONCURxP (Arm B) arms. V. To describe CONCURxP (Arm B) patients and their provider experience with various implementation outcomes. OUTLINE: Patients are randomized into 1 of 2 arms. Non-patient participants are assigned to arm C. ARM A: Patients use the WiseBag medication dispenser and receive access to educational materials every 4 weeks over 12 months. ARM B: Patients use the WiseBag medication dispenser and receive personalized text message reminders, medication tracking and healthcare provider follow ups as part of the CONCURxP platform over 12 months. Patients may complete an interview over 20-30 minutes within 6 months of study completion. ARM C: Participants complete an interview over 20-30 minutes 15-39 months post-first patient enrollment. After completion of study intervention, patients may be followed up to 6 months.

The PLATINUM Trial: Optimizing Chemotherapy for the Second-Line Treatment of Metastatic BRCA1/2 or PALB2-Associated Metastatic Pancreatic Cancer

PRIMARY OBJECTIVES: I. To evaluate and compare overall response rate (ORR) in patients with BRCA1/2 or PALB2 mutant pancreas cancer whose disease has progressed on front-line fluorouracil, irinotecan, leucovorin and oxaliplatin (FOLFIRINOX) treated with nab-paclitaxel, gemcitabine, and cisplatin (NABPLAGEM) = nab-paclitaxel, gemcitabine, and cisplatin (arm 1) versus nab-paclitaxel and gemcitabine (arm 2). (Phase II) II. To evaluate and compare overall survival (OS) time in patients with BRCA1/2 or PALB2 mutant whose disease has progressed on front-line FOLFIRINOX treated with 1) NABPLAGEM = nab-paclitaxel, gemcitabine, and cisplatin (arm 1) versus nab-paclitaxel and gemcitabine (arm 2). (Phase III) SECONDARY OBJECTIVES: I. To evaluate and compare progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) criteria between 2 treatment arms. II. To evaluate and compare duration of response (DoR) between 2 treatment arms. III. To evaluate and compare CA19-9 response (defined as patients with a baseline CA19-9 >= 2x upper limit of normal (ULN) who demonstrate a minimum 25% decrease in CA19-9 at any time point) between 2 treatment arms. IV. To evaluate and compare toxicity profile as assessed by treating clinicians between 2 treatment arms. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive nab-paclitaxel intravenously (IV) over 30-40 minutes, gemcitabine IV over 30-40 minutes, and cisplatin IV over 30-60 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo magnetic resonance imaging (MRI) or computed tomography (CT) throughout the trial. Patients may optionally undergo blood sample collection at baseline and on study. ARM II: Patients receive nab-paclitaxel IV over 30-40 minutes and gemcitabine IV over 30-40 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT throughout the trial. Patients may optionally undergo blood sample collection at baseline and on study. After completion of study treatment, patients are followed up within 30 days and then every 3 months for 2 years or until death, whichever comes first.

An Observational Research Study to Uncover Subtypes of Cancer Cachexia

PRIMARY OBJECTIVE: I. To identify multiple distinct diagnostic subtypes within the syndrome of CC as defined by host characteristics (e.g. cachexia symptoms, physical activity, physical function, blood biomarkers including hemoglobin and albumin, and body composition) at baseline and change in these factors over time in patients with cancer at high risk for CC. SECONDARY OBJECTIVES: I. To determine the association of each CC phenotype with overall survival. II. To validate CC diagnostic phenotypes developed in a separate, independent cachexia observational study performed by our collaborators at Kaiser Permanente. III. To collect human samples of blood, tumor tissue, and medical images and build a large, comprehensive CC database clinically annotated with cancer-related outcomes, cachexia symptoms, and physical function data. EXPLORATORY OBJECTIVE: I. To evaluate for tumor-derived factors contributing to CC by determining the association between interleukin-6 (IL-6) expression in tumor and IL-6 and CC chemokine ligand 2 (CCL2) levels in the blood in patients with CC. OUTLINE: This is an observational study. Patients complete surveys over 30 minutes, undergo physical function tests over 30 minutes, undergo collection of blood and archived tumor samples, and wear actigraph over 24 hours for 7 days to record daily sleep and exercise activity at baseline and 3-month follow-up. Additionally, patients undergo standard of care positron emission tomography (PET)/computed tomography (CT) scans throughout the study and patients' medical records are also reviewed at baseline, 3-month and 1-year follow-up.

A Study of Sigvotatug Vedotin Versus Docetaxel in Previously Treated Non-small Cell Lung Cancer

Cognitive Training for Cancer Related Cognitive Impairment in Breast Cancer Survivors

The goal of this trial is to determine the efficacy of advanced cognitive training for cancer survivors suffering from cancer- and cancer-treatment-related cognitive dysfunction. For millions of cancer survivors, cognitive dysfunction is a prevalent, severe, and persistent problem that has long been associated with poor work-related and health-related outcomes. Evidence suggests that a significant subset of breast cancer survivors (BCS) incur cognitive changes that may persist for years after treatment. Unfortunately, the scientific basis for managing these cognitive changes is extremely limited. Available evidence from pilot studies, including our work, suggests that advanced cognitive training, which is based on the principles of neuroplasticity (ability of brain neurons to re-organize and form new neural networks), may be a viable treatment option. However, previous trials to date have been limited by lack of attention-controlled designs, small samples of BCS, or limited outcome measures. Therefore, to overcome limitations of past studies and build on our pilot results, the purpose of this 2-group, double-blind, randomized controlled trial is to conduct a full-scale efficacy trial to compare advanced cognitive training to attention control in BCS.