Ignite Creation Date:
2025-12-25 @ 2:01 AM
Ignite Modification Date:
2026-02-25 @ 3:00 AM
Study NCT ID:
NCT01948960
Status:
COMPLETED
Last Update Posted:
2018-12-07
First Post:
2013-09-13
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Influence of Exceptional Patient Characteristics on Everolimus Exposure
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D001943', 'term': 'Breast Neoplasms'}], 'ancestors': [{'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D001941', 'term': 'Breast Diseases'}, {'id': 'D012871', 'term': 'Skin Diseases'}, {'id': 'D017437', 'term': 'Skin and Connective Tissue Diseases'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'DIAGNOSTIC', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 56}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2013-08'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2017-10', 'completionDateStruct': {'date': '2018-01-15', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2018-12-05', 'studyFirstSubmitDate': '2013-09-13', 'studyFirstSubmitQcDate': '2013-09-19', 'lastUpdatePostDateStruct': {'date': '2018-12-07', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2013-09-24', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2018-01-15', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'everolimus AUC', 'timeFrame': 'day 14 after start treatment', 'description': 'The primary aim is to show a difference in everolimus exposure (AUC0-24hr) of at least 25% in elderly patients (≥70 years) and obese patients (BMI ≥ 30 kg/m2) compared to the control group (≤ 70 years; BMI ≤ 30 kg/m2), after reaching steady state everolimus pharmacokinetics (day 14, but at least after 7 days of everolimus therapy).'}], 'secondaryOutcomes': [{'measure': 'correlation between early metabolic response and PFS', 'timeFrame': 'within 90 days after start of treatment', 'description': 'To explore and calculate the predictive value of early metabolic response assessment with clinical benefit (PFS defined as disease progression according to RECIST version 1.1 or death, whichever occurs first) as primary outcome measure.\n\nMetabolic response is defined as fractional change (ΔSUV and ΔTLG), comparing the third en second scan with the baseline scan.'}, {'measure': 'correlation between early metabolic response and AUC', 'timeFrame': '15 days after start of treatment', 'description': 'To quantify the correlation between early metabolic response and everolimus exposure (AUC0-24hr) on steady-state pharmacokinetics.\n\nMetabolic response is defined as fractional change (ΔSUV and ΔTLG), comparing the third en second scan with the baseline scan.'}, {'measure': 'effect dose escalation on metabolic respons', 'timeFrame': 'within 36 days after start of treatment', 'description': 'To explore, quantify and describe whether dose escalation in patients who are hypothetically underexposed will result in an increase in metabolic response.\n\nMetabolic response is defined as fractional change (ΔSUV and ΔTLG), comparing the third en second scan with the baseline scan.'}, {'measure': 'correlation between AUC and frequency of adverse event', 'timeFrame': '4 months after start of treatment', 'description': 'To explore, quantify and describe the correlation between everolimus exposure and the frequency of adverse events as graded with CTCAE v4.0.'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['Breast Neoplasms', 'everolimus', 'pharmacokinetics', 'elderly patients', 'obese patients'], 'conditions': ['Breast Neoplasms']}, 'referencesModule': {'references': [{'pmid': '30259313', 'type': 'DERIVED', 'citation': 'Willemsen AECAB, de Geus-Oei LF, de Boer M, Tol J, Kamm Y, de Jong PC, Jonker MA, Vos AH, Grootjans W, de Groot JWB, Mulder SF, Aarntzen EHJG, Gerritsen WR, van Herpen CML, van Erp NP. Everolimus Exposure and Early Metabolic Response as Predictors of Treatment Outcomes in Breast Cancer Patients Treated with Everolimus and Exemestane. Target Oncol. 2018 Oct;13(5):641-648. doi: 10.1007/s11523-018-0596-8.'}], 'seeAlsoLinks': [{'url': 'https://www.ncbi.nlm.nih.gov/pubmed/30259313', 'label': 'Everolimus Exposure and Early Metabolic Response as Predictors of Treatment Outcomes in Breast Cancer Patients Treated with Everolimus and Exemestane'}]}, 'descriptionModule': {'briefSummary': 'A study to determine whether everolimus pharmacokinetics in elderly and obese patients is different compared to control patients.\n\nFurthermore the investigators will investigate the relation between metabolic response assessed with \\[18F\\] Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) and everolimus exposure and clinical benefit.\n\nThe investigators will explore whether dose escalation in patients who are hypothetically underexposed will result in an increase in metabolic response.'}, 'eligibilityModule': {'sex': 'FEMALE', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Adult women (≥ 18 years of age) with metastatic or locally advanced breast cancer not amenable to curative treatment by surgery or radiotherapy.\n* Histological or cytological confirmation of estrogen-receptor positive (ER+) breast cancer\n* Postmenopausal women\n* Radiological or clinical evidence of recurrence or progression on last systemic therapy prior to enrollment.\n* Progression following a non-steroidal aromatase inhibitor\n* Falling into one of the following categories\n\n * elderly patients (age ≥ 70 years and BMI \\< 30 kg/m2); or\n * obese patients (BMI ≥ 30 kg/m2 and age \\< 70 years); or\n * control patients (BMI \\< 30 kg/m2 and age \\< 70 years);\n* Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 x ULN\n* Adequate renal function: calculated creatinine clearance, as estimated by GFR using the MDRD formula, is ≥ 30ml/min/1.73m2\n* Performance status ECOG 0 - 2 (Karnofsky index: 60 - 100)\n* Patient is willing and able to sign the Informed Consent Form prior to screening evaluations\n\nExclusion Criteria:\n\n* Patients aged ≥ 70 years AND BMI ≥ 30 kg/m2\n* HER2-overexpressing patients by local laboratory testing (IHC 3+ staining or in situ hybridization positive).\n* Previous treatment with exemestane or mTOR inhibitors. Except for the treatment with exemestane in the adjuvant setting.\n* Known hypersensitivity to mTOR inhibitors, e.g. sirolimus (rapamycin).\n* Patients with a known history of HIV seropositivity.\n* Any severe and / or uncontrolled medical conditions such as:\n\n * Unstable angina pectoris, serious uncontrolled cardiac arrhythmia\n * Patients with severe hepatic impairment (Child-Pugh A/B/C)\n * Uncontrolled diabetes mellitus\n * Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of study drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome)\n* Patients who test positive for hepatitis B or C\n* Patients being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A within the last 5 days prior to enrollment\n* History of non-compliance to medical regimens\n* Patients unwilling to or unable to comply with the protocol'}, 'identificationModule': {'nctId': 'NCT01948960', 'acronym': 'INPRES', 'briefTitle': 'Influence of Exceptional Patient Characteristics on Everolimus Exposure', 'organization': {'class': 'OTHER', 'fullName': 'Radboud University Medical Center'}, 'officialTitle': 'Influence of Exceptional Patient Characteristics on Everolimus Exposure', 'orgStudyIdInfo': {'id': 'UMCNONCO201301'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'NO_INTERVENTION', 'label': 'standard care', 'description': 'everolimus dose is continued independently of everolimus AUC'}, {'type': 'ACTIVE_COMPARATOR', 'label': 'everolimus dose escalation', 'description': 'patients with an AUC below mean will have dose escalation of everolimus based on their AUC', 'interventionNames': ['Drug: everolimus dose escalation']}], 'interventions': [{'name': 'everolimus dose escalation', 'type': 'DRUG', 'description': 'patients with an AUC below mean will have dose escalation of everolimus based on their AUC', 'armGroupLabels': ['everolimus dose escalation']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Boxmeer', 'country': 'Netherlands', 'facility': 'Maasziekenhuis Pantein', 'geoPoint': {'lat': 51.64667, 'lon': 5.94722}}, {'city': 'Hoofddorp', 'country': 'Netherlands', 'facility': 'Spaarne Gasthuis', 'geoPoint': {'lat': 52.3025, 'lon': 4.68889}}, {'city': 'Maastricht', 'country': 'Netherlands', 'facility': 'Maastricht University Medical Center', 'geoPoint': {'lat': 50.84833, 'lon': 5.68889}}, {'city': 'Nieuwegein', 'country': 'Netherlands', 'facility': 'St. Antonius Ziekenhuis', 'geoPoint': {'lat': 52.02917, 'lon': 5.08056}}, {'city': 'Nijmegen', 'country': 'Netherlands', 'facility': 'Radboud university medical center', 'geoPoint': {'lat': 51.8425, 'lon': 5.85278}}, {'city': 'Uden', 'country': 'Netherlands', 'facility': 'Bernhoven Ziekenhuis', 'geoPoint': {'lat': 51.66083, 'lon': 5.61944}}, {'city': 'Zwolle', 'country': 'Netherlands', 'facility': 'Isala Klinieken', 'geoPoint': {'lat': 52.5125, 'lon': 6.09444}}], 'overallOfficials': [{'name': 'Carla van Herpen, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Radboud university medical center, department of medical oncology'}, {'name': 'Nielka van Erp, PharmD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Radboud university medical center, department of Pharmacy'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Radboud University Medical Center', 'class': 'OTHER'}, 'collaborators': [{'name': 'Novartis', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'SPONSOR'}}}}