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

Gland and Hormone Related Diseases

Adenocarcinoma

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Cystadenocarcinoma, Serous

Fallopian Tube Neoplasms

Carcinoma, Endometrioid

Cystadenocarcinoma

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Genital Neoplasms, Female

Endocrine System Diseases

Gonadal Disorders

Fallopian Tube Diseases

Endometrial Neoplasms

Uterine Neoplasms

Neoplasms, Cystic, Mucinous, and Serous

Ovarian Cancer

Ovarian Epithelial Cancer

Fallopian Tube Cancer

Adenocarcinoma of the Appendix

Immunomodulating Agents

Nivolumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Oral rucaparib and Intravenous (IV) nivolumab (combination therapy)

* Cohort A1
* Cohort A2

Oral rucaparib will be administered twice daily

IV nivolumab will be administered once every 4 weeks

Kathleen N Moore, MD

This is an open label Phase 2, 2-stage, 2-cohort study to evaluate rucaparib in combination with nivolumab in patients with high-grade serous or endometroid ovarian cancer.

Patients entering the following cohorts must have BRCA mutational status confirmed by a central lab:

* Cohort A1: No BRCA mutation in tumor; high level of LOH (loss of heterozygosity)
* Cohort A2: BRCA mutation in tumor

A Study to Evaluate Rucaparib in Combination With Nivolumab in Patients With Selected Solid Tumors (ARIES)

A Phase 2, Open-label Study to Evaluate Rucaparib in Combination With Nivolumab in Patients With Selected Solid Tumors (ARIES)

Objective response rate (ORR) is defined as the percentage of patients with a best confirmed response of complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as assessed by the investigator.

Change in expression of the immune marker PD-L1 pre and post-rucaparib treatment; Cohort A2 only

Objective Response Rate (ORR) is defined as the percentage of patients with a best confirmed response of complete response (CR) or partial response (PR) by RECIST v1.1 as assessed by the investigator or a confirmed response per Gynecological Cancer InterGroup (GCIG) cancer antigen 125 (CA-125 criteria)

Progression-Free Survival (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.

Duration of response (DOR) for any confirmed RECIST CR or PR measured from the date of the first response until the first date that progressive disease (PD) is documented.

Bristol-Myers Squibb

If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class).

Patients received combination therapy, including oral rucaparib 600mg administered twice daily starting on Cycle 1 Day 1 and intravenous (IV) nivolumab 480mg administered on Day 1 of every 4-week cycle, starting on Cycle 2 Day 1.

Cohort A: Ovarian Cancer Cohort

Age, Categorical

The Sponsor made a business decision to discontinue the study due to low accrual.

This study was discontinued by the sponsor so no data is available for this outcome measure.

Objective Response Rate (ORR) by RECIST v1.1 as Assessed by the Investigator

The Effect of Rucaparib on the Immune Microenvironment

ORR by RECIST v1.1 and Gynecological Cancer InterGroup (GCIG) Cancer Antigen 125 (CA-125 Criteria)

Progression-free Survival (PFS)

Duration of Response (DOR)

Nervous System Diseases

Glioma

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

ARIK TZUKERT, DMD

HADAS LAMBERG, PHD

Arik Tzukert, DMD

TALI SIEGAL, MD

IRIS LAVON, PHD

Numerous studies document the ability of tumors to shed DNA into the blood stream. Circulating DNA can thus be recovered for analyses, representing a surrogate tumor material to test for potential applications in disease diagnosis and prognosis.

Detection of genetic alternation is one of the most important tests for cancer patient since they offen correlated with the clinical course, prognosis and chemosensitivity of primary brain tumors. Currently in brain tumor patients these molecular aberrations can be analyzed only on tumor tissue that was obtained at surgery or biopsy.

Paucity of pathologic samples or poor fixation technique often make the tissue samples unassessable for molecular aberrations.

Therefore, the ability to extract tumor DNA from peripheral blood holds a great clinical significance. Still, the molecular aberration evaluated on serum DNA should be correlated and verified by comparison to standard evaluations performed on tumor samples. Our study aim is to evaluate the feasibility of using serum DNA for routine diagnosis of tumor molecular aberrations.

Backround:

Genetic and epigenetic abrasions like loss of hetherozygosity and hypermethylation of gene promoters are common aberration in gliomas. Detection of these aberrations serves as diagnostic and prognostic tool. Examples: 1. oligodendrogliomas patients with combined 1p/19q LOH within the tumor respond better to chemotherapy and have better prognosis, whereas LOH on chromosome 10q is a marker for worse prognosis. 2. GBM patients with hypermethylation of the promoter of methyl-guanine-methyl-transferase (MGMT) in the tumor respond better to alkylating agent and have better prognosis.

As sample materials for diagnosis should be easily accessible by a minimally invasive procedure, there has been much interest in the potential use of nucleic acid markers in the blood of patients with cancer.

It was demonstrated that LOH as well as hypermethylation could be detected in the plasma/serum of patients with a variety of malignancies, suggesting that circulating tumor-associated DNA in the blood of patients can be a key determinant in predicting genetic and epigenetic abrasions in the tumor.

Objectives of the study:

Main objective: to find whether genetic abrasions in serum DNA represent the tumor DNA in patients with brain tumor.

Is tumor DNA can be detected in the serum of only high grade tumors or also in low grade tumor?

Methods:

Blood serum and tumor of patients are obtained anonymously, after the patient has signed a consent form, prior to surgery as part of the procedure for tissue collection for the brain tumor bank at Hadassah.

Part of the tumor is stained with hematoxylin-and-eosin and Histopathologic diagnosis is performed by a pathologist.

DNA is extracted from whole blood, serum and tumor of all patients with low grade or high grade gliomas.

In order to determine whether serum DNA represents the tumor DNA, LOH of 1p,19q,10q,17p,13q, 9p as well as methylation status of MGMT promoter will be tested in DNA samples from blood, serum and tumor.

Serum DNA Analysis: Potential Application for Diagnosis and Prognosis in Brain Cancer.

Hadassah Medical Organization

Adenocarcinoma, Clear Cell

Adenomyoepithelioma

Epithelial-myoepithelial Carcinoma

Paclitaxel

Albumin-Bound Paclitaxel

Carboplatin

Niraparib

Tin Fluorides

3 cycles carboplatin + paclitaxel maintenance therapy with niraparib (starting dose 200 mg QD or 300 mg QD); maintenance continues until disease progression and/or death, unacceptable adverse event/s, patient and/or investigator decision, other protocol stopping criteria.

6 cycles carboplatin + paclitaxel and maintenance therapy with niraparib (starting dose 200 mg QD or 300 mg QD); maintenance continues until disease progression and/or death, unacceptable adverse event/s, patient and/or investigator decision, other protocol stopping criteria.

We hypothesise that recurrence free survival in patients receiving 3 cycles of chemotherapy followed by maintenance with niraparib is not inferior to 6 cycles of chemotherapy followed by niraparib in advanced HRDpositive high-grade ovarian cancer patients with no residual tumor mass following primary tumor debulking.

3 cycles chemotherapy instead of 6 cycles chemotherapy

6 cycles chemotherapy

Maren Keller, Dr.

Katja Gnausch

Jalid Sehouli, Prof. Dr. med.

Multicenter, randomized, open label study including patients with advanced HRDpositive high-grade ovarian cancer, fallopian tube cancer, primary peritoneal cancer and clear cell carcinoma of the ovary with no residual tumor mass following primary tumor debulking to determine recurrence free survival in patients treated with 3 cycles carboplatin + paclitaxel and maintenance therapy with niraparib vs. 6 cycles carboplatin + paclitaxel and maintenance therapy with niraparib.

This is a multicenter, randomized, open label study including patients with advanced (FIGO stage IIIA, IIIB, IIIC, or IV of the 2014 FIGO classification) HRDpositive high-grade ovarian cancer, fallopian tube cancer, primary peritoneal cancer and clear cell carcinoma of the ovary with no residual tumor mass following primary tumor debulking.

The main scope of the trial is to determine recurrence free survival in patients treated with 3 cycles carboplatin + paclitaxel and maintenance therapy with niraparib vs. 6 cycles carboplatin + paclitaxel and maintenance therapy with niraparib.

Patients will be randomized 1:1 to receive either 3 cycles carboplatin + paclitaxel maintenance therapy with niraparib (Arm A) or 6 cycles carboplatin + paclitaxel and maintenance therapy with niraparib (Arm B). Randomization will be performed according to the results of the NGS analysis and stratified either to BRCAm independent of LOH or LOHhigh/ BRCAwt, FIGO stage III vs. IV, and countries. In both of the arms, tumor assessments (CT or MRI) will be performed 9-12 weeks after the start of therapy (after 3rd cycle of chemotherapy), after another 9-12 weeks (during maintenance therapy in Arm A and after the 6th cycle of chemotherapy in Arm B) and every 6 months thereafter. The tumor marker CA-125 will be assessed every 12 weeks in both arms.

During chemotherapy treatment, clinical visits (blood cell counts, detection of toxicity) occur at least every 3 weeks (depending on the chemotherapy regimen). Serum pregnancy tests for WOCBP occur at least every 4 weeks. During maintenance therapy with niraparib, clinical visits (blood cell counts, detection of toxicity) occur every 4 weeks for the first 11 months and every 12 weeks thereafter. Serum pregnancy tests for WOCBP occur at least every 4 weeks. Complete physical examinations will take place every 12 weeks. Safety will be monitored continuously by careful monitoring of all adverse events (AEs) and serious adverse events (SAEs).

About 60 sites in 6 European countries will participate in this study to recruit 640 patients in 36 months.

A Phase II Randomized, Open Label Non-inferiority Study of NiraParib Maintenance After 3 vs. 6 Cycles of Platinum-based Chemotherapy in completeLy debUlked Advanced HRDpositive High-grade Ovarian Cancer patientS in First Line Therapy

A Phase II Randomized, Open Label Non-inferiority Study of NiraParib Maintenance After 3 vs. 6 Cycles of Platinum-based Chemotherapy in completeLy debUlked Advanced HRDpositive High-grade Ovarian Cancer patientS in First Line Therapy (N-Plus)

Scientists may submit a request for scientific use of the data after the first publication. This request shall be examined by the working group and the leading PI. After signing an agreement, the anonymous data can be made available to the scientist (password protected).

Recurrence free survival, defined as time from treatment randomization to the earliest date of assessment of first relapse or death by any cause

Time from randomization until the date of second objective disease progression or death by any cause

Patients are asked to answer the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30). Responses of questions 1-28 are based on a 4-point scale (1=not at all; 4=Very much), with a higher score indicating a high degree of symptomatology and must therefore be assessed negatively. Responses of questions 29 and 30 are based on a 7-point scale (1=Very poor; 7=Excellent), with a higher score indicating a better global health status.

Patients are asked to answer the EORTC QoL Questionnaire-Ovarian Cancer (QLQ-OV28). Responses are based on a 4-point scale (1=Not at all; 4=Very much), with a lower score indicating better symptoms.

Patients are asked to answer the short version of the SF-36 Health Survey (SF-12). The questionnaire contains a total of 12 questions with different response options. For questions 1, 8 and 12 there are 5 (1=excellent, 5=bad), for question 2-3 there are 3 (1=yes, very restricted, 3=no, not restricted at all) and for questions 9-11 there are 6 response options (1= always, 6 = never). Questions 4-7 can be answered with "Yes" or "No".

The safety objective is to characterize the safety and tolerability of 3 vs. 6 cycles of chemotherapy followed by maintenance therapy with niraparib in advanced HRDpositive high-grade ovarian cancer patients with no residual tumor mass following primary tumor debulking. The following safety parameters will be analyzed: adverse events and serious adverse events graded per NCI CTCAE, Version 5.0 criteria with time to onset/recovery, causality and outcome; changes in laboratory values, vital signs since baseline, treatment discontinuations and reason for discontinuation, death and cause of death etc. concomitant medications will be collected with time and reasons of use. These are routine safety parameters collected and analyzed in Phase II /III oncology trials.

The objective is to show that less cycles of chemotherapy are as efficient and at the same time less toxic. Additional cycles of chemotherapy significantly increase toxicity and therefore lead to an increase of costs regarding, e.g. in-patient treatment, concomitant medications to treat (S)AEs.

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
A Study to Evaluate Rucaparib in Combination With Nivolumab in Patients With Selected Solid Tumors (ARIES)	NCT03824704	Epithelial Ovar... Fallopian Tube ... Primary Periton... High Grade Sero... Endometrioid Ad...	Rucaparib Nivolumab	18 Years -	pharmaand GmbH
Serum DNA Analysis: Potential Application for Diagnosis and Prognosis in Brain Cancer.	NCT00265174	Primary Brain T...		-	Hadassah Medical Organization
A Phase II Randomized, Open Label Non-inferiority Study of NiraParib Maintenance After 3 vs. 6 Cycles of Platinum-based Chemotherapy in completeLy debUlked Advanced HRDpositive High-grade Ovarian Cancer patientS in First Line Therapy	NCT05460000	Ovarian Cancer Fallopian Tube ... Primary Periton... Clear Cell Carc...	3 cycles chemot... 6 cycles chemot...	18 Years -	North Eastern German Society of Gynaecological Oncology
A Study to Evaluate Rucaparib in Combination With Nivolumab in Patients With Selected Solid Tumors (ARIES)	NCT03824704	Epithelial Ovar... Fallopian Tube ... Primary Periton... High Grade Sero... Endometrioid Ad...	Rucaparib Nivolumab	18 Years -	pharmaand GmbH

Spots Global Cancer Trial Database for loh

Every month we try and update this database with for loh cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for loh

Every month we try and update this database with for loh cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for loh cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.