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Carcinoma, Renal Cell

Kidney Neoplasms

Carcinoma

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Urogenital Diseases

Female Urogenital Diseases

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Female Urogenital Diseases and Pregnancy Complications

Urologic Diseases

Male Urogenital Diseases

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Renal Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Analgesics

Pembrolizumab

Antibodies

Aldesleukin

Immunoglobulins

Interleukin-2

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Analgesics, Non-Narcotic

Anti-HIV Agents

Anti-Retroviral Agents

Antiviral Agents

Outpatient Intravenous (IV) infusion of Pembrolizumab and Inpatient IV infusion of Interleukin-2.

Pembrolizumab: 200 mg every 3 weeks, 12 doses planned. This is considered the investigational part of the combination. The infusion time is 1 hour.

Interleukin-2: 8 admissions to hospital, each with 5 doses planned. This is considered the standard part of the combination. The standard interleukin-2 dose is 600,000 international units per kilogram per dose, with a maximum of 66,000,000 (for patients over 110 kg, which is 242 pounds). The dose is usually set at the start of the treatment and not adjusted. The infusion time is 15 minutes.

Jad Cuahoud, MD

The main purpose of this study is to evaluate the effects of the interleukin-2 given in combination with pembrolizumab.

Interleukin-2 (IL-2) is also called aldesleukin, or Proleukin™.

Pembrolizumab is also called Keytruda™, or anti-PD-1 antibody.

The treatment is organized into blocks of 9 weeks, with pembrolizumab treatment planned for weeks 1, 4 and 7. On the second and third blocks, interleukin-2 is added, for 5 doses at a time, one dose every 8 hours, on a weekly schedule on the two weeks after the week 1 and the week 4 pembrolizumab doses.

There is no dose escalation portion: The dose and schedule of IL-2 is fixed, 600,000 IU/kg/dose, with a cap of 66 mIU/dose. Doses may be omitted for safety. The dose of pembrolizumab is fixed, flat dose 200 mg/dose.

Interleukin-2 and Pembrolizumab for Metastatic Kidney Cancer

Coordinated High Dose Interleukin-2 (Aldesleukin, Proleukin™) and Pembrolizumab (Anti-PD1, Keytruda™) for Therapy of Metastatic Kidney Cancer

Overall Response According to Immune-related response criteria (irRC). Overall response rate ORR is defined with confirmation of the response status Complete Response (CR) or Partial Response (PR) among the combination treatment population patients; the binomial estimate and its one-sided 95% confidence interval will be reported. CR: Disappearance of all lesions in two consecutive observation not less than 4 weeks apart. PR: ≥50% decrease in tumor burden compared with baseline in two observations at least 4 weeks apart.

Analysis: Overall Survival (OS) of ITT patients using Kaplan-Meier estimate, counting from the eligible date to death from any cause, or censored on end of known follow up, either within this study or in the Prometheus Laboratories sponsored PROCLAIM registry (PROCLAIM Registry to Evaluate the Treatment Patterns and Clinical Response in Malignancy, NCT01415167).

Progression-free survival (PFS) of ITT patients using Kaplan Meier estimate, from the confirmed eligible date to the first occurrence of disease progression or death, from any cause, or lost to follow up, whichever is earliest; or censored at last follow-up during study. Progressive Disease (PD): At least 25% increase in tumor burden compared with nadir (at any single time point) in two consecutive observations at least 4 weeks apart.

Merck Sharp & Dohme LLC

Prometheus Laboratories

H. Lee Moffitt Cancer Center and Research Institute

Pembrolizumab and Interleukin-2

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Jad Chahoud MD, MPH

Overall Response Rate (ORR)

Overall Survival (OS) of Intent to Treat (ITT) Population

Progression Free Survival (PFS)

Overall Study

Clear Cell Renal Cell Carcinoma

Avelumab

Axitinib

Sunitinib

Angiogenesis Inhibitors

Growth Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Avelumab administered at 10 mg/kg IV every two weeks in combination with axitinib, 5 mg PO BID.

Sunitinib given at 50 mg PO QD on schedule 4/2

IV treatment Avelumab administered at 10 mg/kg IV every two weeks

Avelumab (MSB0010718C)

Oral treatment Axitinib given 5 mg PO BID

Axitinib (AG-013736)

Oral treatment Sunitinib given at 50 mg PO QD on schedule 4/2

Pfizer CT.gov Call Center

This is a phase 3 randomized trial evaluating the anti-tumor activity and safety of avelumab in combination with axitinib and of sunitinib monotherapy, administered as first-line treatment, in patients with advanced renal cell carcinoma

A Study of Avelumab With Axitinib Versus Sunitinib In Advanced Renal Cell Cancer (JAVELIN Renal 101)

A PHASE 3, MULTINATIONAL, RANDOMIZED, OPEN-LABEL, PARALLEL-ARM STUDY OF AVELUMAB (MSB0010718C) IN COMBINATION WITH AXITINIB (INLYTA(REGISTERED)) VERSUS SUNITINIB (SUTENT(REGISTERED)) MONOTHERAPY IN THE FIRST-LINE TREATMENT OF PATIENTS WITH ADVANCED RENAL CELL CARCINOMA

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Progression Free Survival (PFS) is the time from randomization to date of first documentation of objective progression of disease assessed by BICR (by RECIST version 1.1) or death due to any cause.

OS is the time from date of randomization to date of death due to any cause.

Number of participants with objective response (ie, confirmed complete or partial response according to RECIST Version 1.1 recorded from randomization until disease progression assessed by BICR or death due to any cause)

DC is defined as complete response (CR), partial response (PR), or stable disease (SD) according to the RECIST v.1.1 recorded from randomization until disease progression assessed by BICR or death due to any cause.

TRR is the time from randomization to first documentation of objective tumor response (CR or PR).

DR is the time from the first documentation of objective tumor response (CR or PR) to the first documentation of objective tumor progression assessed by BICR or death due to any cause

Progression Free Survival (PFS) is the time from randomization to date of first documentation of objective progression of disease assessed by the Investigator (by RECIST version 1.1) or death due to any cause.

Ctrough is defined as the concentration at the end of avelumab dosage interval

Ctrough is defined as the concentration at the end of axitinib dosage interval

Cmax defined as the maximum plasma concentration of axitinib

Biomarker status defined as positive or negative based on a pre-specified scoring algorithm involving, for example, PD-L1 expression and/or quantitation of tumor infiltrating CD8+T lymphocytes as assessed by IHC

OS in biomarker-negative and biomarker-positive subgroups.

The FKSI-19 is a disease-specific instrument that measures disease and treatment-related symptoms specifically in renal cancer patients in 4 domains- Disease Related Symptoms (physical and emotional), Treatment related side effects and Functional and Well-Being . A negative change from Baseline represents a worsening of condition.

EQ-5D Health State Profile: participant rated questionnaire to assess health-related quality of life in terms of a single index value.

PFS as measure of clinical outcome in biomarker-negative and biomarker-positive subgroups.

OR in biomarker-negative and biomarker-positive subgroups

DC in biomarker-negative and biomarker-positive subgroups

TTR in biomarker-negative and biomarker-positive subgroups.

DR in biomarker-negative and biomarker-positive subgroups.

EQ-5D Visual Analogic Scale:patients rated their overall health status from 0 (worst imaginable heath state) to 100 (best imaginable heath state).

TTF is defined as the time from Cycle 1 Day 1 to the date of the first documentation of discontinuation due to an adverse event or death due to study treatment toxicity

Treatment discontinuation is the percentage of patients who discontinue the treatment due to an adverse event or death due to study treatment toxicity

PFS2 is defined as the time from randomization to discontinuation of next line treatment, second objective disease progression, or death from any cause, whichever occurs first.

Pfizer

Sorafenib

* Cycle 1: 400 mg BID sorafenib
* Cycle 2: 600 mg BID sorafenib
* Cycle 3+: 800 mg BID sorafenib

Sorafenib administered in escalating 28-days cycles (400, 600 and 800 mg BID)

Dr. Sandy Srinivas

Determine time-to-progression (TTP) for an escalating dose schedule for subjects with progressive metastatic renal cell carcinoma treated with sorafenib

Sorafenib to be administered as 28-day cycles.

Sorafenib dose escalation by cycle is:

* Cycle 1: 400 mg BID
* Cycle 2: 600 mg BID
* Cycle 3+: 800 mg BID

Within subject dose escalation and maximum dose is dependent on observed tolerability.

Dose escalation only occurs after acceptable tolerability is demonstrated by subject.

Safety and Toxicity Study of Sorafenib in Patients With Kidney Cancer

A Phase 2 Study of Sorafenib in Patients With Metastatic Renal Cell Carcinoma at Stanford University

Stanford University

Associate Professor of Medicine

* Cycle 1: 400 mg BID sorafenib
* Cycle 2: 600 mg BID sorafenib
* Cycle 3+: 800 mg BID sorafenib

Sorafenib: Sorafenib administered in escalating 28-days cycles (400, 600 and 800 mg BID)

Age, Continuous

All subjects enrolled were included in the analysis

Sandy Srinivas, MD

Time-to-progression (TTP)

Symptoms and General Pathology

Gland and Hormone Related Diseases

Neoplasm Metastasis

Hyperparathyroidism

Hyperparathyroidism, Secondary

Renal Insufficiency, Chronic

Renal Insufficiency

Chronic Disease

Disease Attributes

Neoplastic Processes

Parathyroid Diseases

Endocrine System Diseases

Chronic Graft Versus Host Disease

Bone Density Conservation Agents

Cinacalcet

Hormones

Calcium

Calcium, Dietary

Hormone Antagonists

Sensipar

The purpose of this research is to study the effects and safety of Sensipar approved by the Food and Drug Administration (FDA) in patients with kidney failure who are being treated with dialysis and have uncontrolled secondary hyperparathyroidism (HPT).

The purposes of this study are: - To assess the effectiveness of a treatment algorithm that includes Sensipar on bio-intact parathyroid hormone (biPTH), adjusted serum calcium (Ca), serum phosphorus (P), and calcium-phosphorus product (Ca x P) levels in the management of SHPT in CKD subjects on dialysis by determining achievement of National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) Guideline targets. - To assess the use of vitamin D sterols and phosphate binders when Sensipar is incorporated in the treatment of SHPT. - To assess the safety and tolerability of Sensipar.

START: Sensipar Treatment Algorithm to Reach K/DOQI Targets in Chronic Kidney Disease Subjects With Secondary Hyperparathyroidism

Sensipar Treatment Algorithm to Reach K/DOQI Targets in Chronic Kidney Disease Subjects With Secondary Hyperparathyroidism

Amgen

Global Development Leader

Micronutrients

Vasoconstrictor Agents

Vitamins

Other Dietary Supplements

Vitamin D

Cholecalciferol

Calcitriol

Parathyroid Hormone

Vitamin D3

Calciferol

Phytosterol

Participants received standard of care and placebo once daily for 30 weeks during the double-blind phase. During the open-label phase, participants received cinacalcet with standard of care for an additional 30 weeks. The starting dose of cinacalcet was ≤ 0.20 mg/kg based on dry weight, and could be titrated up according to plasma iPTH and serum calcium levels every 4 weeks up to Week 54 to a maximum dose of 4.2 mg/kg.

Participants received standard of care and cinacalcet once daily for 30 weeks during the double-blind phase. The starting dose of cinacalcet was ≤ 0.20 mg/kg based on dry weight, and could be titrated up according to plasma iPTH and serum calcium levels every 4 weeks until Week 24 to a maximum dose of 4.2 mg/kg. During the open-label phase participants continued to receive cinacalcet with standard of care for an additional 30 weeks.

Cinacalcet was prepared for oral administration as both capsules for sprinkling and film coated tablets for swallowing.

cinacalcet capsule

Placebo tablets and capsules for sprinkling identical to active treatment.

placebo

All participants, regardless of treatment assignment, will receive standard of care with vitamin D sterols (calcitriol and its analogs), as prescribed by the treating physician.

Standard of Care

The purpose of this study is to assess the safety and efficacy of adding cinacalcet to the current treatment of secondary hyperparathyroidism in children currently receiving dialysis compared to a treatment regimen that does not include cinacalcet.

Secondary hyperparathyroidism (SHPT) is a condition that can develop early in patients with chronic kidney disease (CKD), usually gets worse over time, and is known to cause problems for patients on dialysis. Children on dialysis can have a wide range of bone and growth issues, and common treatments have a chance of making these things worse by increasing serum calcium and serum phosphorus. Cinacalcet has been shown to be effective in controlling parathyroid hormone (PTH), calcium and phosphorus in adults. The purpose of this study is to show that including cinacalcet in the treatment of SHPT will lower the levels of intact parathyroid hormone (iPTH) in a larger number of pediatric patients with CKD who are receiving dialysis, compared to a treatment regimen that does not include cinacalcet.

Pediatric Chronic Kidney Disease Safety and Efficacy

A Randomized, Double-blind, Placebo Controlled Study to Assess the Efficacy and Safety of Cinacalcet HCl in Pediatric Subjects With Chronic Kidney Disease and Secondary Hyperparathyroidism Receiving Dialysis

The efficacy assessment value is based on the scheduled assessment(s) taken during the efficacy assessment phase (EAP; Weeks 25 - 30). When multiple assessments were available, the average of those was used. If an efficacy measurement during the EAP was missing, the mean of the last 2 available post-baseline values in the dose-titration phase was used. If only one post-baseline value was available, this single value was used.

The efficacy assessment value is based on the scheduled assessment(s) taken during the efficacy assessment phase. When multiple assessments were available, the average of those was used. If an efficacy measurement during the EAP was missing, the mean of the last 2 available postbaseline values in the dose-titration phase was used. If only one post-baseline value was available, this single value was used.

Serum calcium was reported as a corrected value by the central laboratory based on calcium and albumin concentrations: Corrected total calcium (mg/dL) = measured total serum calcium (mg/dL) + 0.8 (4.0 - Serum albumin (g/dL)). The efficacy assessment value is based on the scheduled assessment(s) taken during the efficacy assessment phase. When multiple assessments were available, the average of those was used. If an efficacy measurement during the EAP was missing, the mean of the last 2 available postbaseline values in the dose-titration phase was used. If only one post-baseline value was available, this single value was used."

Linear growth velocity (cm/year) = 52 x change in height (cm) / number of weeks between the two assessments. End of double-blind phase visit was at Week 30 by design but the last assessment in the double-blind phase was used due to the early termination of the study.

Linear growth velocity (cm/year) = 52 x change in height (cm) / number of weeks between the two assessments. End of open-label phase visit was at Week 60 by design but the last assessment in the open-label phase was used due to the early termination of the study.

Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

Double-blind Phase: Placebo

Double-blind Phase: Cinacalcet

Open-label Phase: Previous Placebo

Open-label Phase: Previous Cinacalcet

Placebo

Participants received standard of care and cinacalcet once daily for 30 weeks during the double-blind phase. The starting dose of cinacalcet was ≤ 0.20 mg/kg based on dry weight, and could be titrated up according to plasma iPTH and serum calcium levels every 4 weeks until Week 24 to a maximum dose of 4.2 mg/kg. During the open-label phase participants continued to receive cinacalcet with standard of care for an additional 30 weeks. Regardless of the titration level reached at the last dose of IP in the double-blind phase, all participants started titration at ≤ 0.20 mg/kg based on dry weight.

Total

6 to < 12 years

12 to < 18 years

Age, Customized

White

Black or African American

Other

Race/Ethnicity, Customized

Hispanic or Latino

Not Hispanic or Latino

Intact Parathyroid Hormone (iPTH)

Serum calcium was reported as a corrected value by the central laboratory based on calcium and albumin concentrations:

Corrected total calcium (mg/dL) = measured total serum calcium (mg/dL) + 0.8 (4.0 - Serum albumin (g/dL)).

Corrected Total Serum Calcium

Serum Phosphorous

The study was terminated early with a smaller sample size. However, the study was still sufficiently powered for the double-blind phase. The data collected in the open-label phase is very sparse.

Study Director

A hierarchical testing procedure was used to test the primary and biochemical secondary endpoints (Outcome Measures 1-5). The primary endpoint was tested at a significance level of 0.05. The four biochemical secondary endpoints were to be tested using Holm's method at 0.05 should the primary endpoint achieve a significant result.

Full analysis set, which includes all randomized participants with at least 1 post-baseline assessment.

Percentage of Participants Achieving ≥ 30% Reduction in Mean iPTH From Baseline to the Efficacy Assessment Phase

The secondary endpoint with the smallest p-value was first compared at a significance level of 0.0125. If the p-value was \> 0.0125, all 4 secondary endpoints were non-significant; if ≤ 0.0125, the null hypothesis for that endpoint was rejected. Next, the 2nd smallest p-value was compared at a level of 0.0167; if \> 0.0167, the remaining 3 endpoints were not significant, or, the null hypothesis of that endpoint was rejected. The other 2 endpoints were analyzed similarly, at 0.025 and 0.05.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Interleukin-2 and Pembrolizumab for Metastatic Kidney Cancer	NCT02964078	Kidney Cancer	Pembrolizumab Interleukin-2	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
A Study of Avelumab With Axitinib Versus Sunitinib In Advanced Renal Cell Cancer (JAVELIN Renal 101)	NCT02684006	Renal Cell Canc...	Avelumab (MSB00... Axitinib (AG-01... Sunitinib	18 Years -	Pfizer
Safety and Toxicity Study of Sorafenib in Patients With Kidney Cancer	NCT00854620	Carcinoma, Rena... Kidney Disease Kidney Cancer	Sorafenib	18 Years -	Stanford University
A Study of Avelumab With Axitinib Versus Sunitinib In Advanced Renal Cell Cancer (JAVELIN Renal 101)	NCT02684006	Renal Cell Canc...	Avelumab (MSB00... Axitinib (AG-01... Sunitinib	18 Years -	Pfizer
START: Sensipar Treatment Algorithm to Reach K/DOQI Targets in Chronic Kidney Disease Subjects With Secondary Hyperparathyroidism	NCT00132431	Kidney Disease Secondary Hyper... Chronic Kidney ...	Sensipar	18 Years -	Amgen
Pediatric Chronic Kidney Disease Safety and Efficacy	NCT01277510	Chronic Kidney ... Hyperparathyroi... Hyperparathyroi... Kidney Disease Secondary Hyper...	cinacalcet caps... placebo Standard of Car...	6 Years - 17 Years	Amgen
Oxaliplatin in Cancer Patients With Impaired Kidney Function	NCT00001835	Kidney Disease Neoplasm Neoplasm Metast...	Oxaliplatin	-	National Institutes of Health Clinical Center (CC)
Patient-Centred Innovations for Persons With Multimorbidity - Quebec	NCT02789800	Hypertension Depression Anxiety Musculoskeletal... Arthritis Rheumatoid Arth... Osteoporosis Chronic Obstruc... Asthma Chronic Bronchi... Cardiovascular ... Heart Failure Stroke Transient Ische... Ulcer Gastroesophagea... Irritable Bowel Crohn's Disease Ulcerative Coli... Diverticulosis Chronic Hepatit... Diabetes Thyroid Disorde... Cancer Kidney Disease Urinary Tract P... Dementia Alzheimer's Dis... Hyperlipidemia HIV	DIMAC02	18 Years - 80 Years	Université de Sherbrooke

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