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.

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.
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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