Clinical Trials Actively Recruiting

Objective:

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.

Objective:

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.

Objective:

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.

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 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

Objective:

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).

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:

Objective:

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

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.