Study of Nab-paclitaxel in Sensitive and Refractory Relapsed SCLC (Nabster)

Phase II Study of Nab-paclitaxel in Sensitive and Refractory Relapsed Small Cell Lung Cancer (Nabster Study)

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.

Study Overview

• Status: Unknown
• Conditions: Small Cell Lung Cancer
• Intervention / Treatment: Drug: Nabpaclitaxel

Detailed Description

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

• Study Type: Interventional
• Enrollment (Anticipated): 65
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Alessandria, Italy, 15121
    • Not yet recruiting
    • SC Oncologia - ASO "SS Antonio e Biagio e Cesare Arrigo,Alessandria
    • Principal Investigator: Perluigi Piovano
  • Bergamo, Italy, 24125
    • Not yet recruiting
    • Cliniche Humanitas Gavazzeni
    • Principal Investigator: Giovanni Luca Ceresoli
  • Bergamo, Italy, 24127
    • Recruiting
    • Oncologia Medica, Ospedale Papa Giovanni XXIII
    • Principal Investigator: Anna Bettini, MD
  • Bologna, Italy, 40138
    • Recruiting
    • UO di Oncologia Medica, Azienda Ospedaliero-Universitaria S. Orsola Malpighi di Bologna,
  • Bolzano, Italy, 39100
    • Recruiting
    • Divisione di Oncologia Medica - Ospedale di Bolzano,
  • Brindisi, Italy, 72100
    • Recruiting
    • UOC Oncologia Medica PO A.Perino ASL di Brindisi
  • Cremona, Italy, 26100
    • Not yet recruiting
    • SC di Oncologia, Istituti Ospitalieri di Cremona
    • Principal Investigator: Matteo Brighenti, MD
  • Cuneo, Italy, 12100
    • Recruiting
    • Dipartimento di Oncologia Medica A.O. Santa Croce e Carle Ospedale Carle
  • Firenze, Italy, 50139
    • Not yet recruiting
    • Azienda Ospedaliera Careggi, UO di Oncologia Medica
  • Imola, Italy, 40028
    • Not yet recruiting
    • UOC Oncologia, Azienda USL di Imola, Ospedale Santa Maria della Scaletta
  • Lucca, Italy, 55100
    • Not yet recruiting
    • Dipartimento Oncologico, Azienda USL 2 di Lucca, Ospedale San Luca
    • Principal Investigator: Carmelo Tibaldi, MD
  • Modena, Italy, 41100
    • Recruiting
    • Azienda Ospedaliero-Universitaria di Modena-Policlinico, U.O. di Oncologia Medica ed Ematologia
  • Napoli, Italy, 80131
    • Not yet recruiting
    • S. C. di Oncologia Medica AORN "Antonio Cardarelli"
  • Parma, Italy, 43126
    • Not yet recruiting
    • UOC di Oncologia Medica di Parma, Azienda Ospedaliero Universitaria di Parma
  • Piacenza, Italy, 29121
    • Recruiting
    • Dipartimento di Oncologia e Ematologia, UO di Oncologia Medica Azienda USL di Piacenza
  • Ravenna, Italy, 48121
    • Recruiting
    • Dipartimento di Oncologia Ematologia. UO di Oncologia Medica, AUSL della Romagna, Ospedale Santa Maria delle Croci di Ravenna
    • Principal Investigator: Claudio Dazzi, MD
  • Torino, Italy, 10126
    • Not yet recruiting
    • Azienda Sanitaria Ospedaliera Molinette, U.O. di Oncologia Medica
  • Ferrara
    • Cona, Ferrara, Italy, 44124
      • Recruiting
      • UO di Oncologia Ematologia, Azienda Ospedaliero Universitaria di Ferrara
  • Foggia
    • San Giovanni Rotondo, Foggia, Italy, 71013
      • Not yet recruiting
      • Sezione Pneumo-Oncologica - Medicina Interna I; IRCCS "Casa Sollievo della Sofferenza"
      • Principal Investigator: Vito D'Alessandro, MD
  • Forlì-Cesena
    • Meldola, Forlì-Cesena, Italy, 47014
      • Recruiting
      • Oncologia Medica, IRST. Istituto Scientifico Romagnolo per lo studio e la cura dei Tumori, IRCCS di Meldola
      • Principal Investigator: Angelo Del Monte, MD
  • Lucca
    • Lido di Camaiore, Lucca, Italy, 55043
      • Not yet recruiting
      • Oncologia Medica - Ospedale Versilia
  • MB
    • Monza, MB, Italy, 20900
      • Not yet recruiting
      • SC di Oncologia Medica, A.O. San Gerardo di Monza
      • Principal Investigator: Diego Cortinovis, MD
  • Modena
    • Carpi, Modena, Italy, 41012
      • Recruiting
      • UO Medicina Oncologica Ospedale di Carpi (MO)
      • Principal Investigator: Lucia Longo, MD
  • Varese
    • Saronno, Varese, Italy, 21047
      • Not yet recruiting
      • UOC di Oncologia Medica - Ospedale di Saronno
  • Verona
    • Legnago, Verona, Italy, 37045
      • Not yet recruiting
      • UOC Oncologia Medica, Azienda ULSS21 di Legnago
    • Negrar, Verona, Italy, 37024
      • Not yet recruiting
      • Oncologia Medica, Ospedale Sacro Cuore - Don Calabria - Negrar (VR)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: HEALTH_SERVICES_RESEARCH
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Nab-paclitaxel; Nab-paclitaxel (30-min infusion) 100 mg/sqm weekly on days 1, 8, 15 q 28 days.

Drug: Nabpaclitaxel; Chemotherapy will be continued until a maximum of 6 courses or progressive disease or intolerable toxicity or patient refusal. In patients with confirmed and prolonged disease response, clinical benefit and good tolerance to study drug treatment, the investigators can evaluate to continue therapy beyond 6th cycle, after discussion with Principal Investigator (PI) of the study; Other Names: Abraxane

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary end-point is objective tumor response	It will be evaluated according to standard RECIST 1.1 criteria and will be based on the Investigator's assessment.	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of Toxicity Events: frequency of moderate and severe toxicity events and drop-out rate due to therapy related toxicity	The assessment of safety will be based mainly on the frequency of adverse events. Adverse events will be summarized by presenting the number and percentage of patients having any adverse event, having an adverse event in each body system and having each individual adverse event. Toxicity descriptive tables will be produced which provide the worst degree of toxicity measured over all cycles according to the CTCAE version 4.03	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.
Progression Free Survival (PFS)	will be calculated from the patient registration to the evidence of progressive disease, or death, or the last date the patient was known to be progression-free or alive.	From date of registration until the date of last documented progression or date of death from any cause, assessed up to 100 weeks
Overall Survival (OS)	will be calculated from the registration to death from any cause, or the last date the patient was known to be alive from the registration to death from any cause, or the last date the patient was known to be alive	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

Collaborators and Investigators

• Sponsor: Gruppo Oncologico Italiano di Ricerca Clinica
• Collaborators: Istituto Toscano Tumori; Temas srl; Clirest s.r.l.; Mipharm S.p.A.

Publications and helpful links

General Publications

• 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. Erratum In: Br J Cancer. 2021 Jul;125(2):306.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 7, 2017
• Primary Completion (ANTICIPATED): January 1, 2019
• Study Completion (ANTICIPATED): January 1, 2019

Study Registration Dates

• First Submitted: March 24, 2017
• First Submitted That Met QC Criteria: July 13, 2017
• First Posted (ACTUAL): July 18, 2017

Study Record Updates

• Last Update Posted (ACTUAL): July 26, 2017
• Last Update Submitted That Met QC Criteria: July 24, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Antineoplastic Agents; Albumin-Bound Paclitaxel
• Other Study ID Numbers: GOIRC-02-2016

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes