Clinical Trials Actively Recruiting

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).

Primary Objective:

• To compare the progression-free survival (PFS) of the combination of avutometinib plus defactinib vs Investigator’s Choice of Treatment (ICT) in patients with recurrent LGSOC

Secondary Objectives:

• To compare the combination of avutometinib plus defactinib vs ICT in patients with recurrent LGSOC with regard to additional efficacy parameters
• To characterize the safety and tolerability of combination avutometinib plus defactinib vs ICT in patients with recurrent LGSOC
• To determine the exposure of avutometinib and defactinib in patients with recurrent LGSOC treated with combination of avutometinib plus defactinib
• To assess the health-related quality of life and disease related symptoms in patients with recurrent LGSOC treated with combination avutometinib plus defactinib vs ICT

Primary Objective:

• To determine whether de-intensified chemoradiation for early stage SCCA is able to maintain excellent 2year disease control of 85% or higher while improving anorectal HRQL, compared to standard-dose CRT, as measured by the change in the FIQoL instrument coping/behavior domain from baseline to 1 year.

Secondary Objectives:

• To compare changes in patient-reported outcomes (as per FISI, PROMIS, IIEF, SVQ, and VAS/VuAS instruments) between the experimental and control arm.
• To compare patterns of failure (local and regional relapse versus distant; infield versus out-of-field of radiation), disease control, and overall survival between experimental and control arm.
• To correlate vaginal dilator use during radiation delivery with sexual function.
• To measure changes in serum total testosterone from baseline to up to 12 months after radiation.
• To validate the utility of image features of inguinal and pelvic lymph nodes obtained prior to treatment as a prognostic indicator that can identify patients with early-stage anal squamous cell carcinoma for whom treatment with de-intensified chemo-radiation is appropriate.
• To determine whether an online, interactive educational tool (eContour) may improve the quality of radiation target delineation for anal cancer.
• To determine the incidence of and predictors for cardiovascular toxicity in patients receiving 5-FU or Capecitabine.

Primary Objectives:

• To demonstrate that anti-PD-1 therapy in combination with carboplatin/weekly paclitaxel results in improved progression free survival (PFS) versus systemic chemotherapy alone.

Secondary Objectives:

• To demonstrate that anti-PD-1 therapy in combination with carboplatin/weekly paclitaxel results in improved overall survival (OS) versus systemic chemotherapy alone.
• To demonstrate that anti-PD-1 therapy in combination with carboplatin/weekly paclitaxel results in improved objective response using RECIST v1.1 versus systemic chemotherapy alone.
• To evaluate toxicity profiles of the two regimens.

Primary Objective:

• To determine the efficacy, based on PFS, of mFOLFOX6/bevacizumab plus atezolizumab (combination) as compared to single agent atezolizumab.

Secondary Objectives:

• To compare the overall survival
• To compare the objective response rates (ORR) per RECIST 1.1
• To determine the safety profiles of single agent atezolizumab and the combination of mFOLFOX6 bevacizumab/atezolizumab in patients with dMMR/MSI-H mCRC
• To determine the duration of response
• To determine the duration of stable disease
• To evaluate the rate of progression-free survival at 12 months
• To evaluate the disease control rate (CR + PR + SD) at 12 months

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.

Primary Objectives

Among patients with metastatic extrapulmonary poorly differentiated small cell NEC, to compare overall survival (OS, measured from randomization) in a fixed sequence as follows:

• Compare the combination of induction platinum/etoposide and atezolizumab followed by maintenance atezolizumab (Arm 1) versus induction platinum/etoposide alone (Arm 3)
• Compare the combination of induction platinum/etoposide and atezolizumab followed by observation (Arm 2) versus induction platinum/etoposide alone (Arm 3)
• Compare the combination of induction platinum/etoposide and atezolizumab followed by maintenance atezolizumab (Arm 1) versus the combination of induction platinum/etoposide and atezolizumab followed by observation (Arm 2)

Secondary Objective(s)

• To compare OS, measured from start of observation/maintenance, across arms
• To compare progression-free survival (PFS) (measured from randomization and measured from start of observation/maintenance) across arms
• To compare objective response rate (ORR = confirmed and unconfirmed partial response (PR) + confirmed and unconfirmed complete response (CR)) across arms among patients with measurable disease at randomization
• To compare clinical benefit rate (CBR = confirmed and unconfirmed PR + confirmed and unconfirmed CR + stable disease (SD)) across arms among patients with measurable disease at randomization
• To compare the duration of response (DOR) across arms
• To evaluate the safety and tolerability of each arm

Additional Objective

• To bank tumor and blood samples for future biomarker correlative studies
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Primary Objectives:

• To evaluate the safety and tolerability of FT825 with or without cetuximab following CY/FLU or bendamustine
• To define the RP2D of FT825 with or without cetuximab following CY/FLU or bendamustine

Secondary Objectives:

• To evaluate the antitumor activity of FT825 with or without cetuximab following CY/FLU or bendamustine
• To characterize the PK of FT825 with or without cetuximab following CY/FLU or bendamustine

Primary Objectives:

• To assess the safety and tolerability of study drug
• To identify the recommended dose(s) (RD[s]) and schedule(s) that is (are) safe and biologically effective for study drug administered by intravenous (IV) dosing
• To identify the RD(s) and schedule(s) that is (are) safe and biologically effective for study drug administered by subcutaneous (SC) dosing

Secondary Objectives:

• To characterize the pharmacokinetics (PK) of study drug administered by IV dosing
• To characterize the PK of study drug administered by SC dosing
• To assess the preliminary antitumor activity of study drug

Phase 1 (Dose-escalation and Dose-expansion)

Primary Objectives:

Part A: Dose-escalation:

• To characterize the safety and tolerability of LB1908 and determine the optimal dose or recommended dose for expansion (RDE)

Part B: Dose-expansion:

• To further characterize the safety and tolerability of LB1908 with the RDE identified in the dose-escalation and determine the recommended Phase 2 dose (RP2D)

Secondary Objectives (Parts A and B):

• To evaluate the preliminary efficacy of LB1908
• To characterize the pharmacokinetics of LB1908 in blood
• To evaluate the immunogenicity of LB1908