Clinical Trials Actively Recruiting

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 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:

• Phase II: To assess the efficacy of concurrent definitive therapy followed by nivolumab compared with concurrent definitive therapy followed by observation in terms of progression-free survival (PFS).
• Phase III: To assess the efficacy of concurrent definitive therapy followed by nivolumab compared with concurrent definitive therapy followed by observation in terms of overall survival (OS).

Secondary Objectives:

• To further assess the efficacy of nivolumab compared with observation in terms of the relationship of baseline PD-L1 expression to clinical outcome.
• To evaluate the predictive value of HPV16 E6 and E7 DNA in saliva and plasma, at baseline, 12 weeks and 9 months after completion of radiation on PFS and OS in both arms of the study.
• To evaluate the tumor mutation burden by whole exome sequencing of the initial pretreatment tissue sample as well as samples obtained at the time of progression.
• To evaluate the association of 12 week post therapy FDG PET/CT with PFS and OS.
• To establish the prognostic value of SUVmax of primary tumor or neck nodal metastasis of baseline FDG PET/CT for OS (and/or PFS).
• To correlate SUVmax of primary tumor or nodal metastasis of baseline FDG PET/CT with PD-L1 expression (positive vs. negative).
• To correlate the post therapy (cisplatin + RT) FDG PET/CT with saliva or plasma levels of HPV DNA collected at the time of the standard 3 months PET/CT scan as well as 6 months later (i.e. 9 months post therapy) for both the observation and Nivolumab groups.
• To compare the PET based therapy response assessment (Hopkins criteria) to the RECIST 1.1 assessment at 12 week post chemoradiation therapy, for patients who have a PET/CT scan at 12 weeks.

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.

Primary Objective:

• To compare the rates of lower extremity limb dysfunction (defined as a ≥4-point increase in GCLQ symptom score from baseline) in patients with apparent uterine confined endometrial cancer randomized to one of two lymphatic assessment strategies at time of hysterectomy:
  
  • Arm 1: Sentinel lymph node mapping followed by side-specific lymphadenectomy on sides without a SLN identified according to an NCCN Guidelines approved algorithm.
  • Arm 2: Sentinel lymph node mapping according to an NCCN Guidelines approved algorithm followed by bilateral pelvic +/- para-aortic lymphadenectomy.

Secondary Objectives:

• To compare changes in lower extremity limb circumference in patients with apparent uterine confined endometrial cancer randomized to one of two lymphatic assessment strategies at time of hysterectomy. A subset of study sites will also assess limb changes over time using lower extremity bioimpedance devices.
• To validate the test characteristics of a SLN mapping algorithm including SLN detection rates, rate of perioperative complications, rate of identifying lymphatic metastases, and detection of micrometastases using pathologic ultra-staging.

Primary Objective:

• The primary objective is to determine Progression-free Survival (PFS) by RECIST 1.1.

Key Secondary Objectives:

• To determine Objective Response Rate (ORR) and Duration of Response (DOR) by RECIST 1.1, PFS by RECIST 1.1 (in modified population), PFS by iRECIST, Overall Survival (OS), and safety.

Key Other Objectives:

• To determine ORR by the Gynecological Cancer Intergroup (GCIG) CA-125 criteria, and Clinical Benefit Rate [CBR = (CR + PR + SD ≥ 15 weeks)/total # of patients evaluated by RECIST 1.1 or iRECIST]. Additional analyses of efficacy endpoints in modified population are included.