Clinical Trials Actively Recruiting

Primary Objective(s):

• To compare progression-free survival in participants with metastatic papillary renal cell carcinoma (mPRCC) randomized to cabozantinib with atezolizumab versus cabozantinib alone.
   

Secondary Objective(s):

• To compare overall survival in participants with mPRCC randomized to cabozantinib with atezolizumab versus cabozantinib alone.
• To compare RECIST objective response rate (confirmed and unconfirmed, complete and partial response) in participants with mPRCC randomized to cabozantinib with atezolizumab versus cabozantinib alone.
• To evaluate the quantitative & qualitive adverse events observed in each treatment arm.

Primary Objectives:

• To evaluate the feasibility of molecular characterization based on TMB for
  participant stratification, as assessed by the proportion of participants with less
  than or equal to a 21-day turnaround time for biopsy results in Stage I of the study.
• To evaluate the feasibility of molecular characterization based on TMB and GEP
  (for TIS) for stratification in the overall study (Stage I and Stage II).
• To evaluate the efficacy by overall response rate (ORR – defined as confirmed
  and unconfirmed partial responses plus complete responses) of cabozantinib plus
  nivolumab in each disease cohort, both across and within tumor biomarker
  subgroups.

Secondary Objectives:

• To assess the difference in ORR in each disease cohort between tumor marker
  subgroups separately for each disease cohort.
• To assess safety and tolerability of this treatment in these populations.
• To estimate disease control rate (DCR) in participants receiving cabozantinib plus
  nivolumab in each disease cohort, stratified by tumor biomarkers.
• To estimate progression-free survival (PFS) in participants receiving cabozantinib
  plus nivolumab in each disease cohort, stratified by tumor biomarkers.
• To estimate overall survival (OS) in participants receiving cabozantinib plus
  nivolumab in each disease cohort, stratified by tumor biomarkers.
• To assess the proportion of patients with assay failure, and the time from the date
  of tissue collection to molecular group determination at the end of Stage I.
• To assess turnaround time for TIS for at least 30 patients in Stage I to ensure that
  at least 75% have a turnaround time of <21 days. If TIS is not ready for real-time
  testing when 30 slots remain for Stage I, accrual will be paused until assay
  validation is complete

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 Objective:

• To assess whether participants with early stage TNBC randomized to receive
  anthracycline-free, taxane-platinum neoadjuvant chemotherapy with
  pembrolizumab have non-inferior breast cancer event-free survival (BC-EFS)
  compared to participants randomized to taxane-platinum-anthracycline
  neoadjuvant chemotherapy with pembrolizumab.

Secondary Objectives:

• To compare pathological complete response (pCR) and residual cancer burden
  (RCB) rates by randomized arm.
• To compare pCR and RCB rates between randomized arms by tumor infiltrating
  lymphocytes (TIL) status.
• To compare BC-EFS between randomized arms in the TIL-enriched and non-TIL
  enriched subgroups.
• To compare distant relapse-free survival and overall survival by randomized arm.
• To compare invasive breast cancer-free survival after surgery between
  randomized arms in pCR and residual disease groups.
• To compare the safety and tolerability by randomized arm among those that initiate
  therapy.

Primary Objective:

• To determine if ado-trastuzumab emtansine (T-DM1) shows better progression-free survival (PFS) when compared to docetaxel plus trastuzumab (TH) in recurrent and/or metastatic (R/M) HER2-positive salivary gland cancer (SGC) patients who have not previously received HER2 therapy for unresectable or recurrent and/or metastatic disease, as determined by local assessment.

Secondary Objectives:

• To compare the overall response rate (ORR) by RECIST v1.1 criteria between arms;
• To compare overall survival (OS) between arms;
• To compare toxicity using CTCAE v5.0 criteria between arms;
• To assess patient-reported toxicity, as measured by the PRO-CTCAE, between arms, and explore patient-reported symptomatic adverse events (AEs) for tolerability of each treatment arm as measured by the PRO-CTCAE.

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 Objective:

• To evaluate the antitumor activity of nemvaleukin alfa (‘nemvaleukin’, ALKS 4230)in combination with pembrolizumab as compared with chemotherapy in patients with platinum-resistant ovarian cancer

Secondary Objectives:

• To evaluate the antitumor activity of nemvaleukin in combination with pembrolizumab as compared with chemotherapy
• To evaluate the safety of nemvaleukin in combination with pembrolizumab as compared with chemotherapy

Primary Objectives:

• To evaluate the efficacy of selinexor compared to placebo as maintenance therapy

Key Secondary Objectives:

• To compare overall OS in selinexor and placebo arms

Secondary Objectives:

• To evaluate the safety and tolerability of selinexor
• To compare selinexor and placebo for time to first subsequent therapy
• To compare selinexor and placebo for time to second subsequent therapy
• To compare selinexor and placebo for time until second progression
• To assess the efficacy of selinexor compared to placebo, as assessed by a blinded independent central review (BICR)
• To evaluate health-related quality of life (HRQoL) outcomes

Primary Objectives:

• Phase II: Progression Free Survival
  To evaluate the efficacy of trastuzumab and hyaluronidase-oysk (HERCEPTIN HYLECTA) and pertuzumab, trastuzumab, and hyaluronidase-zzxf (PHESGO) in combination with paclitaxel/carboplatin in patients with HER2 positive endometrial serous carcinoma or carcinosarcoma. Efficacy will be determined via investigator assessed progression free survival (PFS) as assessed by RECIST 1.1. The two experimental arms (Arms 2 and 3) will be compared to the reference arm (Arm 1). If the experimental arms demonstrate superiority to the reference, the experimental arms will be compared to each other.
• Phase III: Overall Survival
  To evaluate the efficacy of trastuzumab and hyaluronidase-oysk (HERCEPTIN HYLECTA) and pertuzumab, trastuzumab, and hyaluronidase-zzxf (PHESGO) in combination with paclitaxel/carboplatin in patients with HER2 positive endometrial serous carcinoma or carcinosarcoma. Efficacy will be determined via investigator assessed overall survival (OS). The two experimental arms (Arms 2 and 3) will be compared to the reference arm (Arm 1). If the experimental arms demonstrate superiority to the reference, the experimental arms will be compared to each other.

Secondary Objectives:

• To evaluate the overall response rate (ORR) in patients with measurable disease. The ORR will be defined as the binomial proportion of evaluable patients with a best overall response of CR or PR (by RECIST 1.1) within 12 months of initiating maintenance therapy.
• To evaluate the duration of objective response in patients with measurable disease as assessed by RECIST 1.1.
• To determine the nature, frequency and degree of toxicity as assessed by CTCAE v.5.0 for each treatment arm.
• To compare QOL, as measured by FACT-En-TOI, in the experimental versus control arms.
• To compare patient-reported treatment-associated symptoms (diarrhea and rash) as measured with the PRO -CTCAE, patient-reported fatigue as measured with the PROMIS-Fatigue short form, and worry concerning side effects of treatment as measured by the item ‘bothered by side effect’, in the FACT-En TOI, respectively, in the experimental and control arms.
• To assess the correlation of HER2 IHC expression and ISH amplification with clinical outcome and response to HER2 targeted therapies.

Primary Objective:

• To evaluate whether breast conservation surgery and endocrine therapy results in a non-inferior rate of invasive or non-invasive ipsilateral breast tumor recurrence (IBTR) compared to breast conservation with breast radiation and endocrine therapy.

Secondary Objectives:

• To evaluate whether breast conservation surgery and endocrine therapy inclusive of any second breast conservation surgery for salvage of IBTR results in a non-inferior rate of overall breast conservation compared to breast conserving surgery, endocrine therapy and radiation for IBTR.
• To evaluate whether breast conservation surgery and endocrine therapy results in a non-inferior rate of invasive ipsilateral breast tumor recurrence (IIBTR) compared to breast conservation, breast radiation, and endocrine therapy.
• To evaluate whether breast conservation surgery and endocrine therapy results in a non-inferior relapse free interval (RFI) compared to breast conservation, breast radiation, and endocrine therapy.
• To evaluate whether breast conservation surgery and endocrine therapy results in a non-inferior distant disease-free survival(DDFS) compared to breast conservation, breast radiation, and endocrine therapy.
• To evaluate whether breast conservation surgery and endocrine therapy results in a non-inferior overall survival (OS) compared to breast conservation, breast radiation, and endocrine therapy.
• To evaluate whether there is a difference in patient-reported breast pain in women who do and do not receive breast radiation.
• To evaluate whether there is a difference in patient-reported worry about recurrence in women who do and do not receive breast radiation.
• To evaluate whether adherence to endocrine therapy following breast conservation surgery alone is non inferior compared to endocrine therapy with breast conservation surgery and breast radiation.