Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Diseases and Abnormalities at or Before Birth

Rare Diseases

Carcinoma

Urinary Bladder Neoplasms

Congenital Abnormalities

Carcinoma, Transitional Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Transitional Cell Carcinoma

Urethral Cancer

Antineoplastic Agents

All Drugs and Chemicals

Poly(ADP-ribose) Polymerase Inhibitors

Rucaparib

Enzyme Inhibitors

The purpose of the ATLAS study is to determine how patients with locally advanced unresectable or metastatic urothelial carcinoma respond to treatment with rucaparib.

Rucaparib in Patients With Locally Advanced or Metastatic Urothelial Carcinoma

A Phase 2, Open-label Study of Rucaparib in Patients With Locally Advanced or Metastatic Urothelial Carcinoma

ORR is defined as the proportion of patients with a confirmed response of complete response (CR) or partial response (PR) by RECIST v1.1 as assessed by the investigator. Complete Response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR), is at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.

PFS is calculated as 1+ the number of days from the first dose of study drug to disease progression by RECIST, as determined by the investigator or death due to any cause, whichever occurs first.

Overall survival (OS) was defined as time from the date of first dose of rucaparib to the date of death due to any cause. Patients without a known date of death were to be censored on the date the patient was last known to be alive. A Kaplan-Meier analysis of OS was planned, however, due to early study termination and limited duration of OS follow-up, a descriptive summary of total deaths are presented. This includes deaths recorded on study (from first dose of study drug until 28 days after last dose of study drug), and deaths recorded in long-term follow-up (from last dose +28 days until death, loss to follow-up, withdrawal of consent, or study closure).

Plasma were collected for trough level PK analysis of rucaparib 1 hour before the morning dose on Cycle 2 Day 1, Cycle 3 Day 1, and Cycle 4 Day 1.

Foundation Medicine

pharmaand GmbH

Patients with HRD status unknown who received continuous dosing with rucaparib 600 mg twice a day (BID) in 28-day cycles. Patients whose tumor genome-wide LOH was not tested or not determined were considered HRD unknown.

HRD Unknown

Patients with HRD status negative who received continuous dosing with rucaparib 600 mg twice a day (BID) in 28-day cycles. Patients whose tumor had genome-wide LOH \< 10% were considered HRD-negative.

HRD Negative

Patients with HRD status positive who received continuous dosing with rucaparib 600 mg twice a day (BID) in 28-day cycles. Patients whose tumor had genome-wide LOH ≥ 10% were considered HRD-positive.

HRD Positive

Overall

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

The study was terminated early based on an interim analysis by the Data Monitoring Committee that demonstrated that ORR did not meet the protocol-defined continuance criteria. There were no confirmed responses observed.

Medical Information Department

Intent-to-treat Population (ITT) with measurable disease at Baseline - The ITT population includes all patients who received at least 1 dose of rucaparib. One patient each in the HRD negative and HRD positive groups did not have measurable disease at Baseline.

Objective Response Rate (ORR) Per RECIST Version 1.1

Intent-to-Treat population - all patients who received at least 1 dose of rucaparib

Progression-free Survival (PFS) According to RECIST v1.1, as Assessed by the Investigator

Overall Survival

Cycle 2 Day 1

Cycle 3 Day 1

Cycle 4 Day 1

Safety population - all patients who received at least 1 dose of rucaparib and who had at least 1 PK sample collected. The number analyzed at each timepoint includes only those participants who remained on study and with viable samples collected at that timepoint.

Pharmacokinetics - Trough (Cmin) Level Rucaparib Concentrations

Overall Study

Respiratory Tract (Lung and Bronchial) Diseases

Skin and Connective Tissue Diseases

Digestive System Diseases

Gland and Hormone Related Diseases

Symptoms and General Pathology

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma, Squamous Cell

Adenocarcinoma

Breast Neoplasms

Esophageal Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Melanoma

Carcinoma, Renal Cell

Squamous Cell Carcinoma of Head and Neck

Melanoma, Cutaneous Malignant

Endometrial Neoplasms

Neoplasm, Residual

Skin Diseases

Breast Diseases

Head and Neck Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Endocrine System Diseases

Gonadal Disorders

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Neoplastic Processes

Esophageal Cancer

Ovarian Cancer

Ovarian Epithelial Cancer

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Fallopian Tube Cancer

Hormones

* Clinical stage T1-4/N0-3/M0 at presentation AND
* Completed preoperative systemic chemotherapy-containing regimen AND
* Underwent definitive surgical resection of the primary tumor AND
* Has pathological evidence of residual invasive carcinoma in the breast and/or axillary lymph nodes AND
* Hormone receptor and HER2 status are known

Includes stage I-III oral cavity, oropharynx, hypopharynx, larynx, nasopharynx, nasal cavity, paranasal sinus, and salivary gland cancers.

Defined as stage IC-III or stage I that has high grade (grade 3-4) or clear cell histology).

Defined as having any of the following: serous or clear cell adenocarcinoma histology (any stage), grade 3 or 4 deeply invasive (T1b or greater) endometrioid carcinoma, stage III disease (any histology).

Defined as high grade (grade 3-4) stage II, stage III or limited (resectable) stage IV treated with curative intent.

Guardant Reveal is a minimal residual disease (MRD) panel for use in recurrence detection of early-stage solid tumors.

Guardant Reveal

Clinical Trial Operations

Study Director

The purpose of ORACLE is to demonstrate the ability of a novel ctDNA assay developed by Guardant Health to detect recurrence in individuals treated for early-stage solid tumors. It is necessary that ctDNA test results are linked to clinical outcomes in order to demonstrate clinical validity for recurrence detection and explore its value in a healthcare environment subject to cost containment.

ORACLE: Observation of ResiduAl Cancer With Liquid Biopsy Evaluation

Recurrence-free interval (RFi) defined as the time from the end of primary treatment until the appearance/occurrence of any recurrence (distant, regional, and/or local) of the Index Cancer. Subjects without recurrence will be censored at the time of last follow-up of their Index Cancer.

Negative predictive value (NPV) defined as the proportion of participants who have ctDNA not detected who have no evidence of recurrence.

1. The proportion of individuals whose indeterminate finding is ultimately confirmed to be disease recurrence who have ctDNA detected at the initial time the indeterminate finding is identified and
2. The proportion of ctDNA not detected participants whose indeterminate findings is ultimately confirmed to be benign.

Sensitivity for local recurrence defined as the proportion of participants who have localized recurrence (e.g., in the absence of distant metastasis) who have ctDNA detected at or before the time of clinical detection of a localized recurrence; using landmark and serial timepoints.

Index Cancer-Specific Survival (ICSS) defined as the time from the date of diagnosis until the date of death from the subject's Index Cancer. Subjects who are still alive at the end of the study observation period will be censored at the time of last known vital status.

Overall Survival (OS) defined as the time from the date of diagnosis until the date of death from any cause. Subjects who are still alive at the end of the study observation period will be censored at the time of last known vital status.

Rate of ctDNA clearance with adjuvant chemotherapy defined as the proportion of patients who have ctDNA detected at the pre-enrollment timepoint whose ctDNA becomes undetectable at the Landmark timepoint.

The primary endpoint, distant recurrence-free interval (D-RFi), will be evaluated for each of the primary study cohorts. D-RFi is defined as the time from the end of primary treatment until the time of diagnosis of a distant recurrence of the Index Cancer. Subjects without a distant recurrence will be censored at the time of last follow-up of their Index Cancer.

Sensitivity defined as the proportion of participants who develop distant recurrence who have ctDNA detected at or before the time of clinical detection of recurrence.

Positive predictive value (PPV) defined as the proportion of participants who have ctDNA detected at the landmark or any surveillance timepoint who recur (either distally or locally).

Lead time defined as the interval between ctDNA detection and clinical detection of recurrence.

Guardant Health, Inc.

Prostatic Neoplasms

Ureteral Neoplasms

Pelvic Neoplasms

Kidney Calculi

Calculi

Nephrolithiasis

Cysts

Ureteral Calculi

Ureterolithiasis

Adrenal Gland Neoplasms

Penile Neoplasms

Genital Neoplasms, Male

Genital Diseases, Male

Kidney Diseases

Pathological Conditions, Anatomical

Penile Diseases

Urolithiasis

Urinary Calculi

Ureteral Diseases

Penile Cancer

Vasoconstrictor Agents

Respiratory System Agents

Epinephrine

Racepinephrine

Epinephryl borate

Patients with urological diseases (renal cell carcinoma, nonfunctioning kidney and adrenal tumor, renal pelvis carcinoma, ureteral tumor, bladder cancer, prostate cancer, pelvic tumor) will be treated by telesurgery.

telesurgery of urological diseases by domestic surgical robot

telesurgery by domestic surgical robot

Haitao Niu, MD

Haitao Niu, PhD

A single-arm clinical trial was designed in this study. The surgeon will perform urological telesurgery for patients using Chinese domestically produced "MicroHand S" surgical robot system. The "MicroHand S" surgical robot system consists of two physically separated subsystems named the "surgeon console" and the "patient side cart". The surgeon console includes a stereo image viewer, two master manipulators, a control panel and several foot pedals. The patient side cart includes a passive arm that can slide in the up-down direction and be adjusted forward and backward, a swivel head that can rotate around the vertical axis, and three slave arms. In addition, surgical instruments and sterile bags are the essential accessories for the "patient side cart". The principle of the telesurgery is as follows: the surgeon console takes the surgeon's input and translates manipulation into a control signal. After network transmission, the signals will be received by the patient side cart and will be used to control the slave robot to manipulate the instruments to perform the operation within the patient's cavity. The 3D images captured by the endoscopic camera will be simultaneously sent back to the screen of the surgeon console as visual feedback. Data between the surgeon console and the patient side cart will be transmitted through a 5G network or other advanced network networking scheme. The surgeon remotely manipulates the slave arms and performs surgeries for patients in remote areas. The safety and efficacy of the robot system in remote clinical treatment will be verified by the primary and the secondary evaluation criteria. One hundred patients with urological diseases will be enrolled in the clinical trial.

Primary evaluation criterion:

The success rate of the surgery. Surgery success is defined as that all surgeries are performed remotely and safely without transfering to other types of surgery, such as open surgery or normal robot-assisted surgery.

Secondary evaluation criteria:

Operative time, blood loss, postoperative pain, preoperative adjusting time, hospitalization time, average network latency, task load, peer recognition, anxiety index.

Patient enrollment:

This experiment aims to investigate the safety and effectiveness of the domestic robot system in clinical urological surgery under the current network networking scheme. It is planned that 100 patients with urinary system diseases will participate in the clinical trial.

Objective: This clinical trial aims to evaluate the efficacy and safety of telesurgery for patients with urological tumors using Chinese independently developed "MicroHand S" Surgical Robot System under the current advanced network networking scheme.

Content: A single-arm clinical trial was designed in this study. The product is domestically produced "MicroHand S" surgical robot system (Shandong Weigao Surgical Robot Co., Ltd, China). The patients will be fully informed and the written informed consent will be signed before the clinical study, According to the inclusion criteria and exclusion criteria, the researchers will conduct a detailed screening to determine whether the patients are suitable for the clinical study. Telesurgery will be conducted for patients who meet the inclusion criteria using the "MicroHand S" surgical robot system. Data between the "surgeon console" and the "patient side cart" will be transmitted through the current advanced network networking scheme. Fifty telesurgeries has been performed for patients with renal tumor, adrenal tumor, or nonfunctional kidney disease in 2021. All the surgeries were completed successfully, which made an positive social influence. In order to explore other indications, 100 subjects will be enrolled in the clinical trial. All diseases will be included if it is applicable to be treated by telesurgery, such as, adrenal tumor, renal tumor, renal cyst, duplex kidney, renal calculi, ureteral calculi, ureteropelvic junction obstruction (UPJO), nonfunctional kidney, renal pelvis tumor, ureteral tumor, bladder cancer, prostate cancer, pelvic tumor, penile cancer, etc. The safety and efficacy of remote clinical treatment using the domestic robot system will be verified according to the primary evaluation criterion, secondary evaluation criteria, and safety evaluation index.

Network connection plan: Two network connection plans were designed in advance to transmit data between the two sites (the master and the slave) in telesurgery. Plan A: Both signals (the control signals and the video signals) were transmitted in a VPN encryption mode under 5G wireless network or other advanced network networking scheme. Plan B: Both signals were transmitted through the dedicated line. When 5G network or other advanced network networking scheme was unstable and the surgery was affected, Plan A could be switched to Plan B to ensure the success of telesurgery. The two sites were also connected through a video conference system for real time communication and coordination.

Primary evaluation criterion: The primary evaluation criterion is the success rate of the surgery.

Secondary evaluation criteria: Secondary evaluation criteria include operative time, intraoperative blood loss, assembly time, postoperative pain, hospital stay, time to first flatus, average network latency, task load index, patient acceptance of telesurgery, peer surgeon acceptance of telesurgery, patient anxiety index, surgeon anxiety index.

Safety evaluation index: (1) Organ and vascular injury events related to the robot, including the following injury events: a. Whether there is adjacent organ injury caused by the robot functional failure during the operation, including liver, spleen and intestinal injury; b. Whether there is hemorrhoea caused by vascular injury caused by the robot functional failure during the operation. (2) Adverse events during the study. (3) Instrument malfunction. a. The communication between the "surgeon console" and the "patient side cart" is strongly disturbed, the slave arms fail to move and malfunction cannot be eliminated after reset and restart. b. by surgical instruments cannot be loosened after the tissue is clamped. c. An alarm sounds when install the instruments. d. Instruments lose efficacy or they are damaged. (4) Vital signs (body temperature, blood pressure, and heart rate). (5) Laboratory examination: blood routine, liver and kidney function, electrolyte.

Researcher selection: In order to strictly ensure the homogeneity and uniformity of researchers, operators are required to have certain qualifications. All surgeons must have at least 5 years of experience in laparoscopic general surgery and at least 1-year experience in robotic surgery. The surgeon will be trained in delay simulation training before the trial. Meanwhile, product training is also required before the trial, and each surgeon must complete at least 20 surgeries with the tested robot. All the trainings above are to help surgeons cross the learning curve.

Background: With the combination of robotic and network communication technology, telesurgery has become a reality. On the one hand, telesurgery can conserve and optimize medical resources, providing high-quality medical services to unbalanced areas, such as rural areas, stricken areas and battlefields. On the other hand, telesurgery can reduce the time spent by patients waiting for treatment and thus prevent diseases from worsening. In recent years, the rapid advancements of the fifth and sixth generation network communication technologies and surgical robotic devices have again boosted the development of telesurgery since the Lindbergh operation and the research of Anvari et al. Especially in a country as vast as China, where the difference of the level of medical care between developed cities and rural areas is huge and the need for telesurgery is enormous. The demand for telemedicine has also risen significantly, particularly since the outbreak of COVID-19. However, as the most challenging components of telemedicine, telesurgery has still developed slowly, and most studies of it are limited to single-center experiences and as such have some inherent limitations. Based on this background, we have successfully conducted preliminary studies in which we verified the safety and feasibility of multiple network plans for telesurgery such as 5G network slicing technology and heterogeneous multilink network converged transmission technology.

In 2021, our research group carried out a multicenter prospective study evaluating efficacy and safety of telesurgery for upper urological tumors using the "Micro Hand S" system robot and a 5G network in Shandong Province, China.

With the prevalence of telesurgery, indications should not limited in upper urological diseases. More indications should be explored. On such basis, this clinical trial was designed and performed.

The Efficacy and Safety of Chinese Domestic Surgical Robot System in Urological Telesurgery

The Efficacy and Safety of Chinese Domestic Surgical Robot System in Urological Telesurgery, an Exploratory Study

The success of the telesurgery is the robot-assisted telesurgery without transfering to other types of surgery, such as open surgery or normal robot-assisted surgery. The number of the success divided by the total number is the success rate.

The operative time is from the time the robot is assembled till the incision is sutured.

Intraoperative blood loss is the total amount of blood loss from the beginning of the operation (after the robot is assembled) to the incision is sutured. The blood loss is estimated by weight. Estimated blood loss (g) = the weight of the gauze wiping up all the blood - the weight of the dry gauze. And 1g = 1ml.

Postoperative pain is assessed by a visual analog scale (VAS) with a range from 0 point (no pain) to 10 points (maximum pain) at 24±2 hours postoperatively.

The assembly time is from the time the robot starts to the time the trocar is connected to the robot arm.

The hospital stay is the total number of days from the admission to the discharge of patients.

Average network latency is monitored by specific software in real time during the telesurgery.

Task load will be evaluated through NASA-TLX questionnaire filled by the surgeons.

Patient acceptance of telesurgery will be assessed through TPSQ questionnaire filled by the patients 1 day before operation.

Peer surgeon acceptance of telesurgery will be systematic reviewed through TAKA questionnaire filled by peer surgeons.

Patient anxiety index will be assessed through TP-SAS questionnaire filled by patients.

Surgeon anxiety index will be assessed through TP-SAS questionnaire filled by operating surgeons and assistant surgeons.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Rucaparib in Patients With Locally Advanced or Metastatic Urothelial Carcinoma	NCT03397394	Bladder Cancer Urothelial Carc... Metastatic Urot... Renal Pelvis Ca... Ureter Carcinom... Urinary Bladder... Urethra Carcino... Muscle Invasive...	Rucaparib	18 Years -	pharmaand GmbH
ORACLE: Observation of ResiduAl Cancer With Liquid Biopsy Evaluation	NCT05059444	Bladder Carcino... Ureter Carcinom... Renal Pelvis Ca... Non-small Cell ... Invasive Breast... Cutaneous Melan... Esophageal Carc... Gastroesophagea... Gastric Adenoca... Pancreatic Aden... Squamous Cell C... Epithelial Ovar... Fallopian Tube ... Endometrial Car... Renal Cell Carc...	Guardant Reveal	18 Years -	Guardant Health, Inc.
The Efficacy and Safety of Chinese Domestic Surgical Robot System in Urological Telesurgery	NCT05739812	Renal Cell Carc... Adrenal Tumor Nonfunctioning ... Renal Pelvis Ca... Ureteral Tumor Bladder Cancer Prostate Cancer Pelvic Tumor Renal Cyst Duplex Kidney Renal Calculi Ureteral Calcul... Ureteropelvic J... Penile Cancer	telesurgery by ...	18 Years - 80 Years	The Affiliated Hospital of Qingdao University
ORACLE: Observation of ResiduAl Cancer With Liquid Biopsy Evaluation	NCT05059444	Bladder Carcino... Ureter Carcinom... Renal Pelvis Ca... Non-small Cell ... Invasive Breast... Cutaneous Melan... Esophageal Carc... Gastroesophagea... Gastric Adenoca... Pancreatic Aden... Squamous Cell C... Epithelial Ovar... Fallopian Tube ... Endometrial Car... Renal Cell Carc...	Guardant Reveal	18 Years -	Guardant Health, Inc.

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