Clinical Trials Actively Recruiting

Primary Objective:

• To compare the non-inferiority of bilateral salpingectomy (BLS) with delayed oophorectomy to bilateral salpingo-oophorectomy (BSO) to reduce the risk of ovarian cancer among women with deleterious BRCA1 germ-line mutations.

Secondary Objectives:

• To prospectively assess estrogen deprivation symptoms in BLS patients as measured by the FACTES sub-scale compared to women in the BSO arm.
• To determine if health-related QOL (FACT) is negatively impacted by menopausal symptoms (menopausal symptom checklist-MSCL), sexual dysfunction (FSFI), and cancer distress (IES) in women who have undergone BLS, in comparison to normative data (MSCL/FACT-ES) and data from BSO patients.
• To assess medical decision making, as measured by the Shared Decision Making Questionnaire (SDM-Q-9) and Decision Regret Scale (DRS), and determine factors associated with the risk of reducing surgical treatment choice.
• To assess adverse events, graded using CTCAE v5.0.

Primary Objectives:

• To determine the maximum tolerated dose (MTD) and the dose-limiting toxicities
  (DLTs) for combination of ATR inhibitor (M1774) and BET inhibitor (ZEN003694) in
  women with recurrent clear cell, endometrioid, and platinum resistant high grade serous
  ovarian carcinoma (HGSOC) and clear cell and endometrioid endometrial carcinoma
  irrespective of ARID1A status (PART I).
• To determine safety and tolerability in ARID1A pathogenic alteration (ARID1AMUT) and
  ARID1A wildtype (ARID1AWT) cohorts (ARID1A is an integral biomarker) in an
  expansion phase (PART II).
• To determine change in pharmacodynamic biomarker expression of ƔH2AX (for ATR
  inhibition, integral biomarker) from pre-treatment and on-treatment tumor samples in
  ARID1AMUT and ARID1AWT expansion cohorts by immunohistochemistry (IHC) (PART
  II).

Secondary Objectives:

• To evaluate change in pharmacodynamic biomarker expression of cmyc (for BET inhibition,
  integrated biomarker) from pre-treatment and on-treatment tumor samples in ARID1AMUT
  and ARID1AWT expansion cohorts by Digital Spatial Profiling (DSP) (PART II).
• To evaluate change in pharmacodynamic biomarker expression of ƔH2AX (for ATR
  inhibition, integrated biomarker) from pre-treatment and on-treatment tumor samples in
  ARID1AMUT and ARID1AWT expansion cohorts by DSP (PART II).
• To investigate if ARID1A protein by IHC and DSP correlates with ARID1A pathogenic
  alteration in pre-treatment tumor biopsy samples (PART II).
• To estimate objective response rate (ORR) and progression free survival (PFS) at 6 months in
  ARID1A pathogenic alteration and wildtype cohorts (PART II).

Dual Primary Objectives:

• To compare progression-free survival (PFS) in frail or selected intermediate fit
  Newly Diagnosed Multiple Myeloma (NDMM) participants treated with VRd-Lite
  induction followed by Lenalidomide maintenance (Arm 1) versus DRd induction
  followed by Lenalidomide maintenance (Arm 2).
• To compare overall survival (OS) in frail or selected intermediate fit NDMM
  participants treated with VRd-Lite induction followed by lenalidomide maintenance
  (Arm 1) versus DRd induction followed by lenalidomide and daratumumab and
  hyaluronidase-fihj maintenance (Arm 3).

Secondary Objectives

• To compare PFS in Arm 1 versus Arm 3
• To compare OS in Arm 1 versus Arm 2.
• To compare OS in Arm 2 versus Arm 3, contingent upon significant results from both dual primary endpoints in favor of the respective experimental arms.
• To compare the overall response rate (ORR) of Arm 1 against the ORR of Arm 2 and Arm 3.
• To assess the safety of Arm 1 with the safety of Arm 2 and Arm 3.
• To explore veinous and arterial thrombo-embolism (VTE) incidence in participants receiving lenalidomide during induction across the three study arms.
• To describe median time to response (CR or better per IMWG criteria, VGPR or better per IMWG criteria, PR or better per IMWG criteria) on the three study arms.

Primary Objective:

• To compare major organ deterioration progression-free survival between participants randomized to the ASCT and non-ASCT arms of this study.

Secondary Objectives

• To compare overall survival (OS) between participants randomized to the ASCT and non-ASCT arms of this study.
• To compare rates of cardiac and renal organ responses between participants randomized to the ASCT and non-ASCT arms of this study.
• To compare rates of cardiac and renal organ progression between participants randomized to the ASCT and non-ASCT arms of the study.
• To compare the frequency and severity of toxicities between participants randomized to the ASCT and non-ASCT arms of this study.
• To compare minimal residual disease (MRD) negativity rates between participants randomized to the ASCT and non-ACST arms of this study.

Primary Objectives:

• Screening and Reassessment (MSRP): To evaluate the feasibility of MATCHBox receiving and organizing all data needed for assignment to a myeloMATCH clinica >trial or Tier Advancement Pathway (TAP) within 72 hours of MDNet receipt of al >required specimens for initial therapy and within 10 days for subsequent therapy.
• Tier Advancement Pathway (TAP): To enable participants who are not matched to an investigational myeloMATCH treatment substudy to receive standard of care (SOC) while remaining on the MSRP to maintain access to later tiers of treatment substudies.

Secondary Objectives:

• Screening and Reassessment (MSRP)
  • To describe the time to generation of all data required for treatment substudy (or TAP) assignment, time to treatment substudy (or TAP) assignment, percent assigned to a myeloMATCH treatment substudy, and the percent of screened participants who register to a myeloMATCH investigational treatment substudy or are assigned to TAP:
    • Separately within each tier of myeloMATCH treatment substudy and analogous TAP assignment (see Section 2.1 for tier definitions)
    • Separately within each clinical basket of myeloMATCH treatment substudies (see Section 2.2 for clinical basket definitions).
    • Over time, across and within the categories above.
• Tier Advancement Pathway (TAP)
  • To evaluate participants for assignment to higher tier treatment substudies within myeloMATCH.
  • To describe, within tier- and basket- levels of TAP, measurable residual disease (MRD) rates and clonal evolution.
  • To describe, within tier- and basket- levels of TAP, remission status and overall survival of participants who receive standard of care therapy.
  • To obtain MDNet specimens for translational medicine and biobanking.

Primary Objectives:

De-Intensification Study:

• To determine whether men with NCCN high risk prostate cancer who are in the lower 2/3 of Decipher genomic risk (< 0.85) can be treated with 12 months ADT plus RT instead of 24 months ADT+RT and experience non-inferior metastasis-free survival.

Intensification Study:

• To determine whether men with NCCN high risk prostate cancer who are in the upper 1/3 of Decipher genomic risk (>0.85) or have node-positive disease by conventional imaging (MRI or CT scan) will have a superior metastasis-free survival (MFS) through treatment intensification with apalutamide added to the standard of RT plus 24 month ADT.

Secondary Objectives for both De-Intensification and Intensification Studies:

• To compare overall survival (OS) between the standard of care (RT plus 24 months of ADT) and either the de-intensification (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide).
• To compare time to PSA failure or start of salvage treatment between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide).
• To compare PSA failure-free survival with non-castrate testosterone and no additional therapies between the standard of care (RT plus 24 months of ADT) and either the deintensification arm  RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide).
• To compare MFS judged based on either standard or molecular imaging between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plusapalutamide).
• To compare prostate cancer-specific mortality between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide).
• To compare testosterone levels at the time of PSA failure and metastases between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide).
• To compare time to testosterone recovery (defined as a T>200) between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide).
• To compare adverse events, both clinician-reported using CTCAE v5.0 and patientreported using PRO-CTCAE items, between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide).

Primary Objective:

De-Intensification Study:

• To determine whether men with National Comprehensive Cancer Network (NCCN) unfavorable intermediate risk (UIR) prostate cancer and lower Decipher genomic risk (Decipher score < 0.40) treated with RT alone instead of 6 months ADT + RT experience non-inferior rate of distant metastasis.

Intensification Study:

• To determine whether men with NCCN UIR prostate cancer who are in the higher genomic risk (Decipher score ≥0.40) will have a superior metastasis-free survival through treatment intensification with darolutamide added to the standard of RT plus 6 months ADT.

Secondary Objectives:

• To compare overall survival (OS) between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.
• To compare time to PSA failure between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.
• To compare metastasis free survival (MFS) based on conventional imaging between the standard of care (RT plus 6 months of ADT) and de-intensification intervention (RT alone).
• To compare MFS based on either conventional and/or molecular imaging between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.
• To compare cumulative incidence of locoregional failure based upon conventional imaging and/ or biopsy between standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months ADT plus darolutamide) interventions.
• To compare cumulative incidence of distant metastasis based upon conventional imaging between standard of care (RT plus 6 months of ADT) and intensification intervention (RT plus 6 months ADT plus darolutamide).
• To compare cumulative incidence of distant metastasis based upon either conventional and/or molecular imaging between standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.
• To compare prostate cancer-specific mortality between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.
• To compare sexual and hormonal related quality of life, as measured by the Expanded Prostate Cancer Index Composite-26 (EPIC), between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.
• To compare fatigue, as measured by the PROMIS-Fatigue instrument, between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.
• To compare cognition, as measured by the Functional Assessment of Chronic Illness Therapy-Cognitive (FACT-Cog) perceived cognitive abilities subscale, between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.

Primary Objectives:

• To compare the overall survival in patients with stage II-IIIC inoperable nodepositive
  non-small cell lung cancer (NSCLC) after image guided, motion-managed
  conventional radiotherapy to the primary tumor and nodal metastases (Arm 1) or after
  image guided, motion-managed stereotactic body radiation therapy (SBRT) to the
  primary tumor followed by conventionally fractionated radiotherapy to nodal
  metastases (Arm 2) both given with concurrent platinum-based chemotherapy.
• To compare progression-free survival between the experimental arm (Arm 2) and
  control arm (Arm 1).

Secondary Objectives:

• To compare objective response rate (as defined by RECIST v 1.1) between the
  experimental arm and control arm
• To compare the rate of local control between the experimental arm and control arm
• To compare patterns of failure (primary, locoregional, or distant) between the
  experimental arm and control arm
• To compare changes in pulmonary function (FEV1 and DLCO assessed at
  randomization and at 6 and 12 months following completion of radiation therapy)
  between the experimental arm and control arm
• To compare changes in quality of life and patient-reported outcomes assessed from
  pre-treatment to 3 months following radiation therapy of each treatment arm
• To determine acute and late toxicity profiles of each treatment arm as measured by
  the CTCAEv5

Primary Objectives:

• To determine if overall survival (OS) is improved with proton beam therapy (PBT) treatment as compared to intensity modulated radiation therapy (IMRT) as part of planned protocol treatment for patients with esophageal cancer.
• To determine if OS with PBT is non-inferior to IMRT as part of planned protocol treatment and that there will be less grade 3+ cardiopulmonary toxicity with PBT than with IMRT.

Secondary Objectives:

• To compare the symptom burden and impact on functioning of patients between treatment modalities based on Patient Reported Outcome (PRO) measures of symptoms using MD Anderson Symptom Inventory (MDASI) and PROMIS-Fatigue;
• To compare the Quality-Adjusted Life Years (QALY) using EQ5D as a health outcome (Kilbridge 2010) between PBT and IMRT, if the protocol primary endpoint is met;
• To assess the pathologic response rate between PBT and IMRT;
• To assess the cost-benefit economic analysis of treatment between radiation modalities;
• To compare the length of hospitalization after protocol surgery between PBT and IMRT;
• To compare the incidence of grade 4 lymphopenia during chemoradiation between PBT and IMRT;
• To compare lymphocyte nadir at first follow-up visit after completion of chemoradiation between PBT & IMRT;
• To estimate the locoregional failure, distant metastatic free survival, and progression-free survival of patients treated with PBT versus IMRT;
• To compare incidence of both early (< 90 days from treatment start) and late (≥ 90 days from treatment start) cardiovascular and pulmonary events between PBT versus IMRT;
• To compare the Total Toxicity Burden (TTB) of IMRT versus PBT based on a composite index of 9 individual cardiopulmonary toxicities.

Exploratory Objectives:

• To collect biospecimens for future analyses, for example to assess cardiac and inflammatory biomarkers in association with treatment complications.