Phase
Condition
Neuroblastoma
Treatment
Dexamethasone
Prednisolone
Farletuzumab ecteribulin
Clinical Study ID
Ages > 18 All Genders
Study Summary
Eligibility Criteria
Inclusion
Inclusion Criteria:
Aged >=18 years
For Dose-Escalation: Females (TNBC, EC and OC) or males/females (NSCLC,adenocarcinoma). Participants with the following disease characteristics: Participants with the following tumor types, each as a separate arm:
TNBC: Histologically confirmed diagnosis of metastatic TNBC (that is, estrogenreceptor (ER) negative/progesterone receptor negative/ human epidermal growthfactor receptor 2 (HER2) negative (defined as immunohistochemistry (IHC) lessthan (<) 2 plus (+) or fluorescence in situ hybridization (FISH) negative)breast cancer). Previously treated with at least one line of systemicanticancer therapy (cytotoxic or targeted anticancer agents) in the metastaticsetting.
NSCLC adenocarcinoma: Histologically or cytologically confirmed metastaticNSCLC adenocarcinoma: participants who have failed previous treatment formetastatic disease, are not indicated or failed epidermal growth factorreceptor (EGFR)-, Anaplastic lymphoma kinase (ALK) -, B-Raf proto-oncogene (BRAF) - or c-ros oncogene 1 (ROS1) - targeted therapy, and for whom noalternative standard therapy exists.
EC: Histologically confirmed diagnosis of advanced, recurrent or metastatic EC.Relapsed or failure of at least one platinum-based regimen or oneimmunotherapy-based regimen.
OC or primary peritoneal cancer or fallopian tube cancer: Histologicallyconfirmed diagnosis of high grade serous epithelial ovarian cancer or primaryperitoneal cancer or fallopian tube cancer. Participants must have:
platinum-resistant disease (defined as progression within 6 months after thelast dose of at least 4 cycles of the last platinum containing chemotherapyregimen)
received up to 4 lines of systemic therapy post development of platinumresistance. For Dose-Confirmation and Dose Optimization: Note: Only participants with histologically confirmed diagnosis of advanced,recurrent, or metastatic EC will be enrolled at sites in France. Ovarian cancer or primary peritoneal cancer or fallopian tube cancer:
Platinum-resistant disease:
For participant with 1 line of platinum-containing therapy: RECIST version 1.1 progression greater than (>) 1 month and less than or equal to (<=) 6months after the last dose of the first platinum-containing chemotherapyregimen (of at least 4 cycles)
For participant with 2-3 lines of platinum-containing therapy: RECISTversion 1.1 progression during or within 6 months after the last dose ofthe 2nd or 3rd platinum-containing chemotherapy regimen.
Have received up to 3 prior lines of systemic therapy and for whom single-agenttherapy is appropriate as the next line of therapy. Participants may have beentreated with up to one line of therapy subsequent to determination ofplatinum-resistance.
Neoadjuvant plus/minus (±) adjuvant will be considered 1 line of therapy.
Maintenance therapy (example, bevacizumab, PARP inhibitors) will beconsidered part of the preceding line of therapy (will not be counted asan independent line of therapy).
Hormonal therapy will be counted as a separate line of therapy unless itwas given as maintenance.
Therapy changed due to toxicity in the absence of progression will beconsidered part of the same line. Endometrial cancer:
Participants must have histologically confirmed diagnosis of advanced,recurrent, or metastatic EC. All histologic (including carcinosarcoma [no morethan one participant at any dose level]) and molecular subtypes will beincluded. Participants may have been treated with an Immune CheckpointInhibitor (ICI) containing regimen (or be ineligible for ICI treatment) andmust have had no more than 2 prior regimens (not including adjuvant therapy ifprogression or recurrent/metastatic disease occurred more than 6 months afterthe completion of the last cycle of adjuvant therapy).
Note: There is no restriction regarding prior hormonal therapy.
Available tumor tissue for FRA expression percent (%) by IHC analysis as assessed ata central laboratory. There is no minimum requirement for FRA expression (%).However, the tumor sample must be evaluable for IHC analysis (that is, of sufficientquality with adequate tumor content). Sample resubmission will be permitted forparticipants with tissue result of "non-evaluable" who are otherwise eligible. Tumorsample submission must be archival formalinfixed, paraffin-embedded (FFPE) tissueblock, or unstained slides sectioned within 45 days from the latest FFPE block, or afresh biopsy sample obtained during screening but prior to initiation of studytreatment.
Radiological disease progression on or after the most recent therapy by investigatorassessment.
Measurable disease meeting the following criteria (confirmed by central radiographicreview, in the Dose-Confirmation Part and in Dose Optimization Part B only):
At least one lesion of >1.0 centimeter (cm) in long axis diameter for non-lymphnodes or >1.5 cm in short axis diameter for lymph nodes that is seriallymeasurable according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 using either computed tomography (CT) or magnetic resonance imaging (MRI),
Lesions that have had external beam radiotherapy (EBRT) or loco-regionaltherapies such as radiofrequency (RF) ablation must show evidence of PD basedon RECIST 1.1 to be deemed a target lesion.
ECOG PS of 0 or 1.
Participants who are expected to survive a minimum of 3 months after the firstadministration of the study drug.
Adequate renal function as evidenced by serum creatinine less than or equal to (<=) 1.5 milligram per deciliter (mg/dL) or calculated creatinine clearance >=50milliliter per (mL) /minute according to a 12 or 24 hour urine collection.
Adequate bone marrow function, as evidenced by:
Absolute neutrophil count (ANC) >=1.0*10^9 per liter (/L)
Hemoglobin (Hgb) >=9.0 gram per deciliter (g/dL)
Platelet count >=75*10^9/L Growth factors or transfusions as per institutionalpractice, are allowed if needed to achieve the above values. Growth factor andplatelet transfusion should not be used within 7 days of initiation of studytreatment.
- Adequate liver function, as evidenced by:
Total bilirubin <=1.5*upper limit of normal (ULN) except for unconjugatedhyperbilirubinemia (example, Gilbert's syndrome)
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <=3ULN (inthe case of liver metastases <=5ULN). Participants with Alkaline Phosphatase (ALP) <=3*ULN unless they and are known to have bone metastases in which casehigher ALP values will also be allowed.
Albumin >3.0 g/dL.
- Participants must undergo a washout period required from the end of prior treatmentto the first administration of the study drug that will be as follows: Prior anticancer therapy:
Prior chemotherapy, surgical therapy, radiation therapy: >3 weeks. Prior chestradiotherapy or pneumonectomy is an exclusion.
Antibody and other biologic therapeutic agents: >=4 weeks.
Endocrine therapy or, small-molecule targeted therapy: >2 weeks.
Immunotherapy >=4 weeks.
Participants with a history of deep vein thrombosis (DVT) within 3 months ofenrollment must be on a stable dose of anticoagulation as demonstrated byappropriate laboratory parameters (depending on the anticoagulant agent) for aminimum of 2 weeks prior to starting study treatment. Anticoagulation must continuewhile on study treatment.
Participants at risk for DVT secondary to central venous catheters or with pastmedical history of DVT or clinical symptoms suggestive of DVT must have venousDoppler ultrasonography to rule out DVT during the screening period and prior toinitiation of study treatment.
If a participant has undergone major surgery, the participant must have recoveredadequately from the toxicity and/or complications from the intervention prior tostarting study treatment.
Resolution of anticancer therapy-related or radiation-related toxicities to Grade 1severity or lower, except for stable sensory neuropathy (Grade <=2), anemia ([haemoglobin] Hgb >=9.0 g/dL), and alopecia (any grade).
Participant must be willing and able to comply with all aspects of the protocol.
Participant must provide written informed consent prior to any study-specificscreening procedures.
Exclusion
Exclusion Criteria:
Participants with endometrial leiomyosarcoma, endometrial stromal sarcoma or othersoft tissue sarcoma histology.
Participants who received previous treatment with any folate receptor targetingagents.
Participants with platinum refractory ovarian cancer (defined as disease progressionduring the initial platinum-based chemotherapy treatment).
Currently enrolled in another clinical study or used any investigational drug ordevice, which in the opinion of the Sponsor may interfere with the study treatment,within the past 28 days or 5 times the half-life (where prior drug therapy fallsunder the parameters these Inclusion Criteria should be followed) of anyinvestigational drug preceding informed consent.
Participants with brain or subdural metastases are not eligible, unless they havecompleted local therapy and have discontinued the use of corticosteroids for thisindication for at least 2 weeks before starting treatment in this study. Brainmetastases must be stable for at least 4 weeks on 2 consecutive scans of the brainbefore starting study treatment.
Diagnosed with meningeal carcinomatosis.
Any other invasive malignancy that required treatment (other than definitivesurgery) or has shown evidence of recurrence/progression (except for non-melanomaskin cancer, or histologically confirmed complete excision of carcinoma in situ)during the 2 years prior to starting study treatment.
Significant cardiovascular impairment. History within 6 months prior to the firstdose of study drug of: congestive heart failure greater than New York HeartAssociation (NYHA) Class II); unstable angina; myocardial infarction; stroke;cardiac arrhythmia associated with hemodynamic instability.
Clinically significant ECG abnormality, including marked prolonged baseline QT ascorrected using Fridericia's formula (QTcF) (repeated demonstration of a QTcFinterval >500 milliseconds [ms]). A history of risk factors for torsade de pointes (example, heart failure, hypokalemia, family history of long QT Syndrome) or the useof concomitant medications that prolong the QTcF.
Known to be Human Immunodeficiency Virus (HIV) positive. Testing at entry notrequired.
Active viral hepatitis (B or C as demonstrated by positive serology). Testing atentry if there are no symptoms or history is not required unless as per localrequirements.
Females who are breastfeeding or pregnant at Screening or Baseline (as documented bya positive beta human chorionic gonadotropin [ß-hCG] or human chorionic gonadotropin [hCG]) with a minimum sensitivity of 25 International units per liter (IU/L) orequivalent units of ß-hCG [or hCG]. A separate baseline assessment is required if anegative screening pregnancy test was obtained more than 72 hours before the firstadministration of the study drug.
Females of childbearing potential who
within 28 days before study entry, did not use a highly effective method ofcontraception, which includes any of the following:
total abstinence (if it is their preferred and usual lifestyle)*
an intrauterine device or intrauterine hormone-releasing system (IUS)
a contraceptive implant
combined (estrogen and progestogen containing) hormonal contraceptionassociated with inhibition of ovulation (oral, intravaginal, transdermal)or progestogen-only hormonal contraception associated with inhibition ofovulation (oral, injectable, implantable). Participants using an oralcontraceptive (participant must be on a stable dose of the same oralcontraceptive product for at least 28 days before dosing and throughoutthe study and for 7 months (5*half-life plus 180 days) after study drugdiscontinuation)
bilateral tubal occlusion
have a vasectomized partner with confirmed azoospermia
do not agree to use a highly effective method of contraception (as describedabove) throughout the entire study period and for 7 months (5*half-life plus 180 days) after study drug discontinuation. For sites outside of the EU, it is permissible that if a highly effective method ofcontraception is not appropriate or acceptable to the participant, then theparticipant must agree to use a medically acceptable method of contraception, thatis, double-barrier methods of contraception such as latex or synthetic condom plusdiaphragm or cervical/vault cap with spermicide. NOTE: All females will beconsidered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, andwithout other known or suspected cause) or have been sterilized surgically (that is,bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all withsurgery at least 1 month before dosing).
*Sexual abstinence is considered a highly effective method only if defined asrefraining from heterosexual intercourse during the entire period of risk associatedwith the study intervention. The reliability of sexual abstinence needs to beevaluated in relation to the duration of the study and the preferred and usuallifestyle of the participant.
For Dose-Escalation only: Males who have not had a successful vasectomy (confirmedazoospermia) or they and their female partners do not meet the criteria above (thatis, not of childbearing potential or practicing highly effective contraceptionthroughout the study period and for 7 months (5half-life plus 180 days) after studydrug discontinuation). If the female partner is pregnant, then males who do notagree to use latex or synthetic condoms throughout the study period and for 4 months (5half-life plus 90 days) after study drug discontinuation. No sperm donation isallowed during the study period and for 4 months (5*half-life plus 90 days) afterstudy drug discontinuation.
Pulmonary Function Test (PFT) abnormalities: FEV1/FVC <0.7, FEV1 or FVC <80%, DLCO <80% or less than the lower limit of normal according to local institutionalstandards.
Current ILD/pneumonitis, or ILD/pneumonitis is suspected at Screening or history ofinterstitial lung disease (ILD)/pneumonitis of any severity includingILD/pneumonitis from prior anticancer therapy.
Current infectious pneumonia, history of viral pneumonia (including COVID-19-relatedinfection) with evidence of persistent radiologic abnormalities.
Lung-specific clinically significant illnesses including, but not limited to anyunderlying pulmonary disorder (example, pulmonary embolism), asthma, chronicobstructive pulmonary disease (COPD), and restrictive lung disease, or currentlyreceiving any medication that is associated with a clinically significant risk ofdeveloping ILD.
Clinically significant pleural or pericardial effusion requiring drainage or ascitesrequiring peritoneal shunt.
Prior pneumonectomy.
History of chest radiotherapy. Participants with history of chest wall radiation (example, history of breast cancer) may be permitted if chest wall radiation isdocumented > 2 years before starting study treatment.
Any autoimmune, connective tissue, or inflammatory disorders (example, rheumatoidarthritis, Sjögren's syndrome, sarcoidosis, etc) where there is documented (orsuspicion of) pulmonary involvement.
A known history of active TB (bacillus tuberculosis).
Scheduled for surgery during the study, other than minor surgery which would notdelay study treatment.
An active clinically significant (in the opinion of the Investigator) infectionrequiring systemic therapy within 2 weeks prior to the first dose of study drug.
Administration of a live, attenuated vaccine within 4 weeks prior to the first doseof study drug, or anticipation that such a live attenuated vaccine will be requiredduring the study. Inactivated vaccines (such as hepatitis A or polio vaccines) arepermitted during the study. Seasonal influenza and COVID-19 vaccines that do notcontain live virus are permitted.
Any prior hypersensitivity to monoclonal antibodies or contraindication to thereceipt of corticosteroids or any of the excipients (investigators should refer tothe prescribing information for the selected corticosteroid).
Known intolerance to either of the components of the study drug.
Any medical or other condition which, in the opinion of the investigator wouldpreclude the participants participation in the clinical study.
Receiving any medication prohibited in combination with the study treatment(s) asdescribed in the product label for eribulin, unless medication was stopped within 7days prior to enrollment.
Known psychiatric or substance abuse disorders that would interfere with cooperationwith the requirements of the trial.
Study Design
Connect with a study center
Centre Antoine Lacassagne Centre Régional de Lutte Contre Le Cancer
Nice, Alpes-Maritimes 6100
FranceActive - Recruiting
ICANS - Institut de cancérologie Strasbourg Europe
Strasbourg, Bas-Rhin 67200
FranceActive - Recruiting
Institut Paoli Calmettes
Marseille, Bouches-du-Rhone 13009
FranceSite Not Available
Hopitaux de La Timone
Marseille, Bouches-du-Rhône 13385
FranceSite Not Available
Centre François Baclesse
Caen, Calvados 14000
FranceSite Not Available
Clinique Amoricaine de Radiologie
Saint-Brieuc, Cote-d'Amore 22000
FranceSite Not Available
Clinique Catherine de Sienne
Nante, Loire-Atlantique 44200
FranceSite Not Available
Clinique Catherine de Sienne
Nantes, Loire-Atlantique 44200
FranceSite Not Available
EDOG Institut de Cancerologie de l'Ouest - PPDS
Nantes, Loire-Atlantique 44000
FranceActive - Recruiting
Centre Oscar Lambret
Lille, Nord 59000
FranceSite Not Available
Centre Hospitalier de la Cote Basque
Bayonne, Pyrenees-Atlantiques 64109
FranceSite Not Available
Centre Leon Berard Centre Regional de Lutte Contre
Lyon, Rhone 69008
FranceActive - Recruiting
Centre Léon Bérard Centre Régional de Lutte Contre Le Cancer Rhône Alpes
Lyon, Rhône 69008
FranceActive - Recruiting
CLCC - Gustave Roussy Cancer
Villejuif, Val-de-Marne 94805
FranceActive - Recruiting
Hopital Cochin
Paris, 75679
FranceSite Not Available
Hôpital de la Croix Saint-Simon
Paris, 75020
FranceSite Not Available
ICO Badalona-H.U. Germans Trias i Pujol
Badalona, Barcelona 8916
SpainActive - Recruiting
Hospital Universitario Vall d'Hebron - PPDS
Barcelona, 8035
SpainActive - Recruiting
Clinica Universidad Navarra - Madrid
Madrid, 28027
SpainSite Not Available
Hospital Clinico San Carlos
Madrid, 28040
SpainActive - Recruiting
Hospital General Universitario Gregorio Marañon
Madrid, 28007
SpainSite Not Available
Hospital Universitario Ramon y Cajal
Madrid, 28304
SpainActive - Recruiting
Hospital Universitario de Toledo
Toledo, 45007
SpainSite Not Available
Fundacion Instituto Valenciano de Oncologia
Valencia, 46009
SpainActive - Recruiting
Hospital Clinico Universitario de Valencia
Valencia, 46010
SpainActive - Recruiting
Hospital Universitari i Politecnic La Fe de Valencia
Valencia, 46013
SpainActive - Recruiting
Belfasr City Hospital
Belfast, Antrim BT9 7AB
United KingdomSite Not Available
Lancashire Clinical Research Facility, Royal Preston Hospital
Preston, Lancashire PR2 9HT
United KingdomActive - Recruiting
Mount Vernon Cancer Centre
Northwood, Middlesex HA6 2RN
United KingdomSite Not Available
Velindre Cancer Centre - PPDS
Cardiff, South Glamorgan CF14 2TL
United KingdomActive - Recruiting
The Royal Marsden
Sutton, Surrey SM2 5PT
United KingdomSite Not Available
Beatson West of Scotland Cancer Centre - PPDS
Glasgow, G12 0YN
United KingdomActive - Recruiting
Guys and St Thomas's Hospital
London, SE1 9RT
United KingdomActive - Recruiting
The Christie NHS Foundation Trust - PPDS
Manchester, M20 4BX
United KingdomActive - Recruiting
Arizona Clinical Research Center - Hunt - PPDS
Tucson, Arizona 85715
United StatesSite Not Available
University of Arkansas For Medical Sciences
Little Rock, Arkansas 72205
United StatesSite Not Available
Stanford University School of Medicine
Stanford, California 94305
United StatesActive - Recruiting
H Lee Moffitt Cancer Center and Research Institute
Tampa, Florida 33612
United StatesActive - Recruiting
Winship Cancer Institute, Emory University
Atlanta, Georgia 30322
United StatesSite Not Available
Georgia Cancer Center at Augusta University
Augusta, Georgia 30912
United StatesActive - Recruiting
Northwestern University
Chicago, Illinois 60611
United StatesActive - Recruiting
Orchard Healthcare Research Inc
Skokie, Illinois 60077
United StatesSite Not Available
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland 21231
United StatesActive - Recruiting
Henry Ford Health System
Detroit, Michigan 48202
United StatesSite Not Available
Memorial Sloan Kettering Cancer Center
Detroit, Michigan 48201-2013
United StatesSite Not Available
MD Anderson Cancer Center at Cooper
Camden, New Jersey 08103
United StatesCompleted
Barbara Ann Karmanos Cancer Institute
New Brunswick, New Jersey 08901-1914
United StatesSite Not Available
MD Anderson Cancer Center at Cooper
Voorhees, New Jersey 08043
United StatesSite Not Available
Columbia University Medical Center
New York, New York 10032
United StatesActive - Recruiting
Memorial Sloan Kettering Cancer Center
New York, New York 11065
United StatesActive - Recruiting
University of Cincinnati Medical Center
Cincinnati, Ohio 45219
United StatesActive - Recruiting
Ohio State University
Columbus, Ohio 43210
United StatesCompleted
Oregon Health and Science University
Portland, Oregon 97239
United StatesSite Not Available
Chattanooga's Program In Women's Oncology
Chattanooga, Tennessee 37403
United StatesCompleted
University of Texas MD Anderson Cancer Center
Houston, Texas 77030
United StatesSite Not Available
University of Texas MD Anderson Cancer Centre
Houston, Texas 77030
United StatesSite Not Available
University of Virginia Health System
Charlottesville, Virginia 22908
United StatesCompleted
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