Clinical trial NCT03219762: Study of Nab-paclitaxel in Sensitive and Refractory Relapsed SCLC
Official title: Phase II Study of Nab-paclitaxel in Sensitive and Refractory Relapsed Small Cell Lung Cancer (Nabster Study)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Small Cell Lung Cancer
Lead sponsor: Gruppo Oncologico Italiano di Ricerca Clinica
Sponsor class: OTHER
Collaborators: name: Temas srl
name: Clirest s.r.l.
name: Mipharm S.p.A.
name: Istituto Toscano Tumori
First posted: 2017-07-18
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open label, multicentre, study
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: Evaluate the activity and safety of Nab-paclitaxel in patients with sensitive or refractory SCLC who relapsed after cisplatin or carboplatin and etoposide first-line chemotherapy.

Detailed description: Phase II study of NAB-paclitaxel in SensiTivE and Refractory relapsed SCLC

Eligibility criteria: Inclusion Criteria:

* Pathologically (histology or cytology) confirmed diagnosis of small cell lung cancer (SCLC) or large-cell neuroendocrine carcinoma (LCNEC) or poorly differentiated (G3) neuroendocrine cancer of the lung (according to WHO classification 2015)
* Male or female and ≥ 18 years of age
* Life expectancy ≥ 12 weeks
* Have progressed after or during platinum-based standard chemotherapy regimen (cisplatin or carboplatin and etoposide) for first-line treatment of SCLC, either limited stage (LD) or extensive stage (ED) disease and have not received any other treatment (except for immunotherapy as maintenance treatment), including re-treatment with front-line regimen
* Have measurable disease per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1); clear radiological evidence of disease progression after first-line therapy has to be documented; no previous radiotherapy on the only site of measurable or evaluable disease, unless that site had subsequent evidence of progression
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
* Patients with treated brain metastases with stable lesions for at least 2 weeks and off steroids or on a stable dose of steroids. Radiotherapy must have been completed a minimum of 14 days prior to registration, and patients must have recovered from AEs related to radiotherapy to \< grade 1 (except alopecia)
* For Females: must be postmenopausal (defined as occurring 12 months after last menstrual period) before the screening visit, or are surgically sterile. If they are of childbearing potential, a negative serum pregnancy test prior to study entry has to be documented; furthermore, they agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form (ICF) through 30 days after the last dose of study drug, or agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject
* For Males: even if surgically sterilized (i.e. post-vasectomy status) agree to practice effective barrier contraception during the entire study treatment period and through 6 months after the last dose of study drug, or practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject
* Screening clinical laboratory values as specified below:

  * Absolute neutrophil count (ANC) ≥ 1500/mm3, platelet count ≥ 100,000/mm3 and haemoglobin ≥ 9 g/dL
  * Total bilirubin \< 1.5 the institutional upper limit of normal (ULN)
  * Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \< 2.5 the institutional ULN (\< 5 if liver function test elevations are due to liver metastases)
  * Creatinine \< 1.5 institutional ULN or estimated creatinine clearance using the Cockcroft-Gault formula ≥ 30 mL/minute for patients with creatinine levels above institutional limits
* Stable medical condition, including the absence of acute exacerbations of chronic illnesses, serious infections, or major surgery within 4 weeks before registration, and otherwise noted in other inclusion/exclusion criteria
* Recovered (i.e., ≤ Grade 1 toxicity) from effects of prior anticancer therapy, except alopecia
* Prior radiotherapy is allowed provided that it has been completed more than 2 weeks before starting Nab-paclitaxel
* Ability to comply with protocol requirements
* The patient or the patient's legal representative has to be able to provide written informed consent. Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care

Exclusion Criteria:

* Any prior not platinum-based chemotherapy treatment for SCLC or large-cell neuroendocrine carcinoma (LCNEC) or poorly differentiated (G3) neuroendocrine cancer of the lung (according WHO classification 2015) (immunotherapy is allowed as maintenance treatment)
* Prior treatment with Nab-paclitaxel, paclitaxel or any other taxane agent
* Known hypersensitivity to Cremophor EL®, paclitaxel, or its components
* Any comorbid condition or unresolved toxicity that would preclude administration of weekly Nab-paclitaxel
* Prior history of Grade ≥ 2 neurotoxicity that is not resolved to ≤ Grade 1
* Patients with symptomatic and/or progressive brain metastases or with carcinomatous meningitis
* Diagnosed with or treated for another malignancy within 3 years before the first dose of study drug, or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in situ of any type may be enrolled in the study if they have undergone complete resection and no evidence of active disease is present
* History of myocardial infarction, unstable symptomatic ischemic heart disease, uncontrolled hypertension despite appropriate medical therapy, any ongoing cardiac arrhythmias of Grade \> 2, thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), or any other cardiac condition (egg, pericardial effusion or restrictive cardiomyopathy) within 6 months before receiving the first dose of study drug. Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed. Patients with a pacemaker may be enrolled in the study upon discussion with the project clinician
* Infection requiring IV antibiotic therapy or other serious infection within 14 days before the first dose of study drug
* For female subjects: positive serum pregnancy test, pregnancy or breast feeding
* Surgery within 3 weeks (or 2 weeks for a minor surgery) before study enrolment and not fully recovered to baseline or to a stable clinical status. Insertion of a vascular device is allowed
* Unwilling or unable to comply with the protocol or cooperate fully with the investigator and site personnel

Primary outcomes:
measure: The primary end-point is objective tumor response
timeFrame: From date of the first enrolment until the date of last documented progression or date of death from any cause, assessed up to 100 weeks.
Secondary outcomes:
measure: Frequency of Toxicity Events: frequency of moderate and severe toxicity events and drop-out rate due to therapy related toxicity
timeFrame: From date of the first enrolment until the date of last documented progression or date of death from any cause, assessed up to 100 weeks.
measure: Progression Free Survival (PFS)
timeFrame: From date of registration until the date of last documented progression or date of death from any cause, assessed up to 100 weeks
measure: Overall Survival (OS)
timeFrame: From date of patient enrolment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Other outcomes:
Locations:
city: Cona
country: Italy
facility: UO di Oncologia Ematologia, Azienda Ospedaliero Universitaria di Ferrara
state: Ferrara
city: San Giovanni Rotondo
country: Italy
facility: Sezione Pneumo-Oncologica - Medicina Interna I; IRCCS "Casa Sollievo della Sofferenza"
state: Foggia
city: Meldola
country: Italy
facility: Oncologia Medica, IRST. Istituto Scientifico Romagnolo per lo studio e la cura dei Tumori, IRCCS di Meldola
state: Forlì-Cesena
city: Lido di Camaiore
country: Italy
facility: Oncologia Medica - Ospedale Versilia
state: Lucca
city: Monza
country: Italy
facility: SC di Oncologia Medica, A.O. San Gerardo di Monza
state: MB
city: Carpi
country: Italy
facility: UO Medicina Oncologica Ospedale di Carpi (MO)
state: Modena
city: Saronno
country: Italy
facility: UOC di Oncologia Medica - Ospedale di Saronno
state: Varese
city: Legnago
country: Italy
facility: UOC Oncologia Medica, Azienda ULSS21 di Legnago
state: Verona
city: Negrar
country: Italy
facility: Oncologia Medica, Ospedale Sacro Cuore - Don Calabria - Negrar (VR)
state: Verona
city: Alessandria
country: Italy
facility: SC Oncologia - ASO "SS Antonio e Biagio e Cesare Arrigo,Alessandria
city: Bergamo
country: Italy
facility: Cliniche Humanitas Gavazzeni
city: Bergamo
country: Italy
facility: Oncologia Medica, Ospedale Papa Giovanni XXIII
city: Bologna
country: Italy
facility: UO di Oncologia Medica, Azienda Ospedaliero-Universitaria S. Orsola Malpighi di Bologna,
city: Bolzano
country: Italy
facility: Divisione di Oncologia Medica - Ospedale di Bolzano,
city: Brindisi
country: Italy
facility: UOC Oncologia Medica PO A.Perino ASL di Brindisi
city: Cremona
country: Italy
facility: SC di Oncologia, Istituti Ospitalieri di Cremona
city: Cuneo
country: Italy
facility: Dipartimento di Oncologia Medica A.O. Santa Croce e Carle Ospedale Carle
city: Firenze
country: Italy
facility: Azienda Ospedaliera Careggi, UO di Oncologia Medica
city: Imola
country: Italy
facility: UOC Oncologia, Azienda USL di Imola, Ospedale Santa Maria della Scaletta
city: Lucca
country: Italy
facility: Dipartimento Oncologico, Azienda USL 2 di Lucca, Ospedale San Luca
city: Modena
country: Italy
facility: Azienda Ospedaliero-Universitaria di Modena-Policlinico, U.O. di Oncologia Medica ed Ematologia
city: Napoli
country: Italy
facility: S. C. di Oncologia Medica AORN "Antonio Cardarelli"
city: Parma
country: Italy
facility: UOC di Oncologia Medica di Parma, Azienda Ospedaliero Universitaria di Parma
city: Piacenza
country: Italy
facility: Dipartimento di Oncologia e Ematologia, UO di Oncologia Medica Azienda USL di Piacenza
city: Ravenna
country: Italy
facility: Dipartimento di Oncologia Ematologia. UO di Oncologia Medica, AUSL della Romagna, Ospedale Santa Maria delle Croci di Ravenna
city: Torino
country: Italy
facility: Azienda Sanitaria Ospedaliera Molinette, U.O. di Oncologia Medica
Study officials:
References:
citation: Gelsomino F, Tiseo M, Barbieri F, Riccardi F, Cavanna L, Frassoldati A, Delmonte A, Longo L, Dazzi C, Cinieri S, Colantonio I, Sperandi F, Lamberti G, Brocchi S, Tofani L, Boni L, Ardizzoni A. Phase 2 study of NAB-paclitaxel in SensiTivE and refractory relapsed small cell lung cancer (SCLC) (NABSTER TRIAL). Br J Cancer. 2020 Jul;123(1):26-32. doi: 10.1038/s41416-020-0845-3. Epub 2020 Apr 29.