Clinical Trials Actively Recruiting

Objective:

Primary Objective:

• To compare the efficacy of single-agent olaparib and the combination of olaparib and cediranib (and potentially other combination arms that may be added by subsequent amendment) versus single agent cediranib as measured by progression free survival (PFS), in patients with recurrent, persistent or metastatic endometrial cancer.

Secondary Objectives:

• To compare the efficacy of single-agent olaparib and the combination of olaparib and cediranib (and potentially other combination arms that may be added by subsequent amendment) versus single-agent cediranib as measured by overall survival (OS) in patients with recurrent, persistent or metastatic endometrial cancer.
• To compare the efficacy of single-agent olaparib and the combination of olaparib and cediranib (and potentially other combination arms may be added by subsequent amendment versus single-agent cediranib as measured by response rate in patients with recurrent, persistent or metastatic endometrial cancer.
• To assess the safety and tolerability of single–agent cediranib, single-agent olaparib, and the combination of olaparib and cediranib (and potentially other combination arms may be added by subsequent amendment).
• To assess if mutations in DNA Homologous Repair Genes (assayed prior to all treatment and prior to the study treatment) are predictive of response to olaparib alone or in combination with cediranib. (Integrated Biomarker)
• To assess if markers of angiogenesis in serial plasma samples are associated with response to cediranib alone or in combination with olaparib. (Integrated Biomarker)

Objective:
Primary Objective:

• To examine if letrozole monotherapy/maintenance is non-inferior to IV paclitaxel/carboplatin and maintenance letrozole with respect to PFS in women with stage II-IV primary low-grade serous carcinoma of the ovary or peritoneum after primary surgical cytoreduction.

Secondary Objectives:

• To compare the nature, frequency and maximum degree of toxicity as assessed by CTCAE v5.0 for each treatment arm.
• To compare the relative frequency of objective tumor response in those with measurable disease after cytoreductive surgery for each treatment arm.
• To compare overall survival for each treatment arm.
• To compare the CT\L and L\L arms with respect to patients adherence to letrozole therapy as measured by pill counts.

Objective:

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.

Objective:
Primary Objective:

• To compare overall survival (OS) between the two treatment arms with lenalidomide as the comparator arm and lenalidomide + daratumumab/rHuPH20 as the experimental arm in post-autologous transplant multiple myeloma (MM) patients.

Secondary Objectives of First Randomization:

• To compare the best overall response rate (ORR), including partial remission (PR), very good partial remission (VGPR), and complete remission (CR, sCR) in the subset of patients not in PR at randomization to lenalidomide versus lenalidomide + daratumumab/rHuPH20 in this patient population.
• To compare progression-free survival (PFS) between the study arms in this patient population.
• To evaluate MRD-negativity on the two treatment arms at randomization (Registration Step 2), and to compare MRD-negativity rate at 12, 24 (second randomization), 36, and 48 months after first randomization between lenalidomide and lenalidomide + daratumumab/rHuPH20 in this patient population.
• To compare toxicities and tolerability of long term therapy between the study arms.

Objectives of Second Randomization:

• To compare overall survival (OS) between MRD negative patients randomized to continued lenalidomide vs. discontinued lenalidomide from the time of second randomization in this patient population.
• To compare overall survival (OS) between MRD negative patients randomized to continued lenalidomide + daratumumab/rHuPH20 vs. discontinued lenalidomide + daratumumab/rHuPH20 from time of second randomization in this patient population.

Objective:
Primary Objective(s):

• To assess whether prophylactic beta blocker therapy with carvedilol compared with no intervention reduces the risk of subsequent cardiac dysfunction in patients with metastatic breast cancer receiving trastuzumab?based HER-2 targeted therapy.

Secondary Objective(s):

• To assess whether prophylactic beta blocker therapy with carvedilol compared with no intervention reduces the risk of predefined subsequent cardiac events in patients with metastatic breast cancer receiving trastuzumab?based HER-2 targeted therapy.
• To evaluate if prophylactic carvedilol compared with no intervention results in a longer time to first interruption of trastuzumab?based HER-2 targeted therapy due to either cardiac dysfunction or events.
• To assess whether prophylactic beta blocker therapy with carvedilol compared with no intervention reduces the risk of subsequent cardiac dysfunction OR events in this population.
• To establish and prospectively collect a predefined panel of baseline core cardiovascular measures and develop a predictive model of cardiac dysfunction (see Section 11.2).
• To evaluate the rate of cardiac dysfunction in an observational arm consisting of individuals otherwise eligible for the study except for use of beta blockers, angiotensin receptor blocker (ARB), or angiotensin converting enzyme (ACE) inhibitors for other medical reasons.

Objective:

Primary Objective:

• To evaluate the progression free survival (PFS) of advanced pancreatic cancer patients with germline BRCA1 or BRCA2 mutations treated with olaparib + pembrolizumab compared to olaparib alone as maintenance therapy.

Secondary Objectives:

• To evaluate the safety and tolerability associated with the combination of olaparib + pembrolizumab vs. olaparib alone as maintenance therapy.
• To evaluate the overall survival (OS) of patients treated with olaparib + pembrolizumab compared to olaparib alone as maintenance therapy.
• To evaluate the overall response rate (ORR) by RECIST 1.1, including confirmed and unconfirmed, complete and partial response, of patients treated with olaparib + pembrolizumab compared to olaparib alone, in the subset of patients with measurable disease.
• To evaluate the overall response rate (ORR) by immune RECIST, including confirmed and unconfirmed, complete and partial response, of patients treated with olaparib + pembrolizumab compared to olaparib alone, in the subset of patients with measurable disease.
• To evaluate the duration of response (DoR) by RECIST 1.1 in patients treated with olaparib + pembrolizumab compared to olaparib alone.

Banking Objective:

• To bank tissue and blood specimens for future correlative studies.

Objective:

Primary Objectives Phase II:

To determine if patient-reported neck and shoulder function and related quality of life (QOL) at 6 months after surgery using the Neck Dissection Impairment Index (NDII) is superior with Sentinel Lymph Node (SLN) biopsy compared to Elective Neck Dissection (END) for treatment of early-stage oral cavity squamous cell carcinoma (OCSCC) (cT1-2N0).

Primary Objectives Phase III:

• To determine if disease-free survival (DFS) is non-inferior with SLN biopsy compared to END for treatment of early-stage OCSCC (cT1-2N0).
• To determine if patient-reported neck and shoulder function and related QOL at 6 months after surgery using NDII is superior with SLN biopsy compared to END for treatment of early-stage OCSCC (cT1-2N0).

Secondary Objectives:

• To compare patterns of failure (local-regional relapse and distant metastasis) between surgical arms.
• To measure and compare overall survival (OS) between surgical arms.
• To measure and compare the toxicity of the two surgical arms.
• To measure longitudinal patient-reported neck and shoulder function and related QOL between surgical arms, using the following instruments:
• Neck Dissection Impairment Index (NDII)
• Abbreviated Disabilities of the Arm, Shoulder and Hand (QuickDASH)
• Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N)
• To assess the length of hospitalization, post-operative drain placement, and operative morbidity between arms.
• To estimate the negative predictive rate of FDG PET/CT for N0 neck in patients with T1 and T1-2 oral cavity squamous cell cancer (OCSCC) patients in the END arm.
• To assess nodal metastases rates between arms.
• To assess the pathologic false omission rate (FOR) in the SLN biopsy arm.
• To determine if patient-reported neck and shoulder function and related QOL at 6 months after surgery using the NDII is superior with the SLN biopsy compared to the END in low-risk patients.

Objective:

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.

Objective:

Primary Objectives:

• Phase 1: To investigate the safety and tolerability of ZN-c3 in combination with niraparib, including identification of the MTD and RP2D
• Phase 2: To investigate the antitumor activity of ZN-c3 in combination with niraparib

Secondary Objectives:

• To further investigate the antitumor activity of ZN-c3 in combination with niraparib
• To investigate the OS of subjects receiving ZN-c3 in combination with niraparib
• To investigate the safety and tolerability of ZN-c3 in combination with niraparib
• To evaluate changes in PROs and quality of life

Objective:

Objectives (UPLIFT):

Primary in Pivotal Cohort (UPLIFT):

• Determine the confirmed investigator-assessed objective response rate of XMT-1536 (upifitamab rilsodotin) in patients with higher sodium-dependent phosphate transport protein 2b (NaPi2b) expressing platinum-resistant high-grade serous ovarian cancer (HGSOC), including cancers of ovarian, fallopian tube or primary peritoneal origin)

Secondary in UPLIFT:

• Assess the investigator-assessed objective response rate of XMT-1536 (upifitamab rilsodotin) regardless of NaPi2b expression.
• Assess the objective response rate by independent radiology review (IRR) for patients with higher NaPi2b and overall.
• Assess the duration of objective response (DOR) in patients who achieve a response.
• Assess the incidence and severity of adverse events (AEs).

Exploratory in DES, EXP and UPLIFT:

• Retrospectively evaluate the association of objective response with tumor expression of genes other than NaPi2b, or other tumor molecular and histologic features

Exploratory in UPLIFT:

• Assess the disease control rate (DCR)
• Assess the progression-free survival (PFS)
• Assess the overall survival (OS)
• Assess the population PK
• Assess the relationship of XMT-1536 (upifitamab rilsodotin) exposure to efficacy and safety outcomes.
• Assess development of anti-drug antibody and neutralizing antibody in response to XMT-1536 (upifitamab rilsodotin) exposure