Trial Title:
Atezolizumab and Rechallenge Chemotherapy in Relapsed Patients With Extensive-stage Small Cell Lung Cancer (ES-SCLC).
NCT ID:
NCT06663098
Condition:
Extensive Stage Small Cell Lung Cancer (ES-SCLC)
Conditions: Official terms:
Lung Neoplasms
Small Cell Lung Carcinoma
Carboplatin
Etoposide
Atezolizumab
Conditions: Keywords:
Extensive-stage small cell lung cancer
atezolizumab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Atezolizumab
Description:
1200 mg IV on day 1 of every 21 days, during induction phase and maintenance phase
Arm group label:
Arm 1
Other name:
humanized IgG1 monoclonal antibody against PD-L1
Intervention type:
Drug
Intervention name:
Carboplatin
Description:
AUC 4 or 5, depending on patient's characteristics, on day 1 every 21 days during
induction phase
Arm group label:
Arm 1
Other name:
re-challenge chemotherapy
Intervention type:
Drug
Intervention name:
Etoposide
Description:
80 mg/sqm or 100 mg/sqm, depending on patient's characteristics, on days 1-2-3 of every
21 days
Arm group label:
Arm 1
Other name:
re-challenge chemotherapy
Summary:
The goal of this clinical trial is to learn if a combination of atezolizumab and standard
chemotherapy works to treat sensitive Extensive-stage Small Cell Lung Cancer, progressing
after first-line of treatment.
The main questions it aims to answer are:
- Does combination of atezolizumab and standard chemotherapy increase overall
survival?
- What medical problems do participants have when taking combination of atezolizumab
and standard chemotherapy?
Participants will:
- take atezolizumab and standard chemotherapy every 3 weeks for 4 cycles and than
atezolizumab every 3 weeks up to 18 cycles.
- visit the clinic once every 3 weeks for checkups and tests
- perform Radiological assessments after 6 weeks and then every 12 weeks to determine
response to treatment.
Detailed description:
The CARRY-ON study is a multicenter, prospective, open-label single-arm phase II trial,
designed to seek for a signal of efficacy of continuing PD-L1 inhibition in patients with
sensitive relapse ES-SCLC by adding atezolizumab to rechallenge carboplatin-etoposide
chemotherapy. The trial is planned to enroll 142 patients with sensitive relapse ES-SCLC
from 25 Italian centers. Sensitive relapse is defined as SCLC relapsed or progressed to
first-line chemo-immunotherapy with PD-L1 inhibition (with either atezolizumab or
durvalumab) at least 60 days after the last chemotherapy administration. Eligible
patients will receive re-challenge chemotherapy (either carboplatin AUC 4 on day 1 plus
etoposide 80 mg/m2 days 1-3 or carboplatin AUC 5 on day 1 plus etoposide 100 mg/m2 days
1-3, at investigator's choice) plus atezolizumab 1200 mg flat dosing on day 1 every 3
weeks until PD, unacceptable toxicity or to a maximum of 4 cycles (induction phase)
followed by atezolizumab 1200 mg flat dosing every 3 weeks (maintenance phase) until
completion of 1 year of maintenance (up to 18 cycles), progressive disease, unacceptable
toxicity, patient refusal or loss of clinical benefit (investigator's choice), whichever
occur first.
Subjects will attend clinical visits at regular intervals to receive trial treatment and
for efficacy and safety assessments. All subjects will be monitored continuously for any
AE while on study treatment.
Radiological assessment will be performed by computed tomography (CT) scan at week 6 (± 7
days), at week 12 (± 7 days) and every 12 weeks (± 7 days) thereafter.
The duration of the study is expected to be a maximum of 45 months. The study recruitment
period is expected to be approximately 24 months, maximum treatment duration will be 15
months (3 months of induction and 12 months of maintenance), and subsequent survival
follow-up will be a maximum of 6 months.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Diagnosis of small-cell lung cancer (SCLC) (according to WHO classification 2015)
confirmed at pathology (histology or cytology).
2. Male or female and ≥ 18 years of age.
3. Life expectancy ≥ 12 weeks.
4. Disease progression at least 60 days after the completion of first-line chemotherapy
consisting of at least 4 cycles of platinum-etoposide plus either atezolizumab or
durvalumab and have not received any other treatment (except for immunotherapy as
maintenance treatment); the 60 day-interval is calculated from the date of the last
chemotherapy administration to the date of the first radiologically documented
progressive disease.
5. No previous radiotherapy on the only one site disease progression, unless that site
had subsequent evidence of progressive disease.
6. Eastern Cooperative Oncology Group performance status (ECOG PS) ≤2.
7. Patients with treated brain metastases (or untreated but asymptomatic) and off
steroids or on a stable dose of steroids (≤10 mg of prednisone-equivalent) are also
eligible. 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)
8. 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 5 months 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.
9. 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.
10. Normal baseline laboratory values as specified below:
- Absolute neutrophil count (ANC) ≥1500/mm3
- Platelet count ≥ 100 x 109/L (≥100,000/μL) without transfusion
- Hemoglobin ≥ 90 g/L (≥ 9 g/dL); patients may be transfused to meet this
criterion.
- Total bilirubin < 1.5x the institutional upper limit of normal (ULN)
- Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 2.5x
the institutional ULN (< 5x if liver function test elevations are due to liver
metastases)
- Creatinine < 1.5x institutional ULN or estimated creatinine clearance using the
Cockcroft-Gault formula ≥ 30 mL/minute for patients with creatinine levels
above institutional limits
- For patients not receiving therapeutic anticoagulation: INR and aPTT ≤ 1.5 x
ULN
- Negative HIV test at screening {with the following exception: patients with a
positive HIV test at screening are eligible provided they are stable on
anti-retroviral therapy, have a CD4 count ≥ 200/μL, and have an undetectable
viral load}
- Negative hepatitis B surface antigen (HBsAg) test at screening
- Positive hepatitis B surface antibody (HBsAb) test at screening, or negative
HBsAb at screening accompanied by either of the following:
- Negative total hepatitis B core antibody (HBcAb)
- Positive total HBcAb test followed by a negative (per local laboratory
definition) hepatitis B virus (HBV) DNA testNegative hepatitis C virus
(HCV) antibody test at screening, or positive HCV antibody test followed
by a negative HCV RNA test at screening The HCV RNA test must be performed
for patients who have a positive HCV antibody test.
11. 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.
12. Recovered (i.e., ≤ grade 1 toxicity) from effects of prior anticancer therapy,
except alopecia.
13. Prior radiotherapy is allowed provided that it has been completed more than 2 weeks
before starting protocol treatment and patients have recovered from AEs related to
radiotherapy to < grade 1
14. Ability to comply with protocol requirements.
15. 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:
1. More than 1 line of prior treatment for ES-SCLC.
2. First-line treatment without either atezolizumab or durvalumab.
3. First-line chemotherapy other than platinum-etoposide.
4. Less than 4 cycles of first-line platinum-etoposide.
5. Presence of resistant relapse (progressive disease within 60 days from the end of
first-line chemotherapy) or refractory disease (progressive disease during the first
4 cycles of first-line chemoimmunotherapy).
6. Symptomatic brain metastases or spinal cord compression (CT or MRI of the head is
required within 4 weeks prior to randomization)requiring immediate radiotherapy for
palliation. Patients with treated brain metastases (or untreated but asymptomatic)
and off steroids or on a stable dose of steroids (≤10 mg of prednisone-equivalent)
are also eligible provided that all of the following criteria are met:
- If treated, at least 14 days between the end of stereotactic radiotherapy or
whole brain radiotherapy and initiation of study treatment and recovery from
AEs related to radiotherapy to ≤ grade 1 (except alopecia), or at least 28 days
between neurosurgical resection and initiation of study treatment;
- Anticonvulsant therapy at a stable dose is permitted;
- Metastases are limited to the cerebellum or the supratentorial region (i.e., no
metastases to the midbrain, pons, medulla or spinal cord);
- There is no evidence of interim intracranial progression between completion of
CNS directed therapy (if administered) and initiation of study treatment.
7. Evidence of leptomeningeal disease.
8. Any comorbid condition or unresolved toxicity that would preclude administration of
second-line chemotherapy.
9. Patient has received a live-virus vaccination within 30 days of planned treatment
start. Seasonal flu vaccines and COVID vaccines that do not contain live virus are
permitted. Note: Patients, if enrolled, should not receive live vaccine whilst
receiving IP and up to 30 days after the last dose of IP.
10. Treatment with systemic immunostimulatory agents (including, but not limited to,
interferon and interleukin 2 [IL-2]) within 4 weeks or 5 drug elimination half-lives
(whichever is longer) prior to initiation of study treatment except for PD-L1
inhibitor maintenance as part of first-line treatment.
11. Any condition requiring systemic treatment with either corticosteroids or other
immunosuppressive medications within 14 days of registration . The following are
exceptions to this criterion:
- Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra
articular injection);
- Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of
prednisone or its equivalent;
- Steroids as premedication for hypersensitivity reactions (e.g., CT scan
premedication).
12. 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.
13. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment
other than those in the present study. Concurrent use of hormonal therapy for
non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
14. Treatment with any other investigational agent within 30 days prior to starting
study treatment, or concurrent enrolment in another clinical study, unless it is an
observational (non-interventional) clinical study or during the follow-up period of
an interventional study.
15. Infection requiring intravenous antibiotic therapy or other serious infection within
14 days before the first dose of study drug.
16. Prior allogeneic stem cell or solid organ transplantation.
17. For female subjects: positive serum pregnancy test, pregnancy, or breastfeeding.
18. Surgery within 4 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.
19. Patients who experienced medically significant or NCI CTCAE Grade 3 or higher
toxicities in response to first-line immunotherapy
20. Unwilling or unable to comply with the protocol or cooperate fully with the
investigator and site personnel.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Centro di Riferimento Oncologico di Aviano (CRO) IRCCS
Address:
City:
Aviano (PN)
Zip:
33081
Country:
Italy
Contact:
Last name:
Alessandro Del Conte, MD
Phone:
0039-0434-399464
Email:
alessandro.delconte@cro.it
Investigator:
Last name:
Alessandro Del Conte
Email:
Principal Investigator
Facility:
Name:
IRCCS Istituto Tumori "Giovanni Paolo II"
Address:
City:
Bari
Zip:
70124
Country:
Italy
Contact:
Last name:
Vito Longo, MD
Phone:
0039-080555-5478
Email:
v.longo@oncologico.bari.it
Investigator:
Last name:
Vito Longo
Email:
Principal Investigator
Facility:
Name:
IRCCS Azienda Ospedaliero_Universitaria di Bologna
Address:
City:
Bologna
Zip:
40138
Country:
Italy
Contact:
Last name:
Andrea Ardizzoni, MD
Phone:
0039-051-2142206
Email:
andrea.ardizzoni@aosp.bo.it
Facility:
Name:
UOC Medicina Oncologica
Address:
City:
Carpi
Zip:
41012
Country:
Italy
Contact:
Last name:
Donatella Giardina, MD
Phone:
0039-0596-59294
Email:
d.giardina@ausl.mo.it
Investigator:
Last name:
Donatella Giardina
Email:
Principal Investigator
Facility:
Name:
ASST Cremona
Address:
City:
Cremona
Zip:
26100
Country:
Italy
Contact:
Last name:
Matteo Brighenti, MD
Phone:
0039-0372-408040
Email:
MATTEO.BRIGHENTI@ASST-CREMONA.it
Investigator:
Last name:
Matteo Brighenti
Email:
Principal Investigator
Facility:
Name:
Azienda Ospedaliera S. Croce e Carle di Cuneo
Address:
City:
Cuneo
Zip:
12100
Country:
Italy
Contact:
Last name:
Ida Colantonio, MD
Phone:
0039-0171-616350
Email:
colantonio.i@ospedale.cuneo.it
Investigator:
Last name:
Ida Colantonio
Email:
Principal Investigator
Facility:
Name:
AOU Careggi
Address:
City:
Firenze
Zip:
50134
Country:
Italy
Contact:
Last name:
Francesca Mazzoni
Phone:
0039-055-947298
Email:
mazzonifr@aou-careggi.toscana.it
Investigator:
Last name:
Francesca Mazzoni
Email:
Principal Investigator
Facility:
Name:
Azienda USL Toscana nord-ovest Ospedale Versilia
Address:
City:
Lido Di Camaiore
Zip:
55041
Country:
Italy
Contact:
Last name:
Andrea Camerino, MD
Phone:
0039-0584-6057282
Email:
andrea.camerino@uslnordovest.toscana.it
Facility:
Name:
Azienda USL Toscana Nord Ovest - Ospedale San Luca
Address:
City:
Lucca
Zip:
55100
Country:
Italy
Contact:
Last name:
Editta Baldini, MD
Phone:
0039-0583-449545
Email:
editta.baldini@usinordovest.toscana.it
Investigator:
Last name:
Editta Baldini
Email:
Principal Investigator
Facility:
Name:
Istituto Scientifico Romagnolo per lo studio e la cura dei Tumori (IRST) "Dino Amadori"
Address:
City:
Meldola (FC)
Zip:
47014
Country:
Italy
Contact:
Last name:
Angelo Delmonte, MD
Phone:
0039-0543-739100
Email:
angelo.delmonte@irst.emr.it
Investigator:
Last name:
Angelo Delmonte
Email:
Principal Investigator
Facility:
Name:
IRCCS Ospedale San Raffaele
Address:
City:
Milano
Zip:
20132
Country:
Italy
Contact:
Last name:
Roberto Ferrara, MD
Phone:
0039-02-2643-4138
Email:
ferrara.roberto@hsr.it
Investigator:
Last name:
Roberto Ferrara
Email:
Principal Investigator
Facility:
Name:
AOU Policlinico di Modena
Address:
City:
Modena
Zip:
41125
Country:
Italy
Contact:
Last name:
Federica Bertolini, MD
Phone:
0039-059-422-3252
Email:
bertolini.federica@aou.mo.it
Facility:
Name:
ASST San Gerardo dei Tintori Foundation
Address:
City:
Monza
Zip:
20900
Country:
Italy
Contact:
Last name:
Diego L Cortinovis, MD
Phone:
0039-233-9575
Email:
diegoluigi.cortinovis@irccs-sangerardo.it
Investigator:
Last name:
Diego Luigi Cortinovis
Email:
Principal Investigator
Facility:
Name:
AORN A. Cardarelli
Address:
City:
Napoli
Zip:
80131
Country:
Italy
Contact:
Last name:
Ferdinando Riccardi, MD
Phone:
0039-081747-2221
Email:
ferdinando.riccardi@aocardarelli.it
Investigator:
Last name:
Ferdinando Cardarelli
Email:
Principal Investigator
Facility:
Name:
AOU San Luigi Gonzaga
Address:
City:
Orbassano (TO)
Zip:
10043
Country:
Italy
Contact:
Last name:
Enrica Capelletto, MD
Phone:
0039-011-9026539
Email:
enrica.capelletto@gmail.com
Facility:
Name:
Istituto Oncologico Veneto
Address:
City:
Padova
Zip:
35128
Country:
Italy
Contact:
Last name:
Giulia Pasello, MD
Phone:
0039-049-8215608
Email:
giulia.pasello@iov.veneto.it
Investigator:
Last name:
Giulia Pasello
Email:
Principal Investigator
Facility:
Name:
UOC di Oncologia Medica
Address:
City:
Parma
Zip:
43126
Country:
Italy
Contact:
Last name:
Alessandro Leonetti, MD
Phone:
0039-0521-702660
Email:
aleonetti@ao.pr.it
Investigator:
Last name:
Alessandro Leonetti
Email:
Principal Investigator
Facility:
Name:
Azienda Ospedaliera Santa Maria della Misericordia
Address:
City:
Perugia
Zip:
06132
Country:
Italy
Contact:
Last name:
Giulio Metro, MD
Phone:
0039-0755-83695
Email:
giulio.metro@ospedale.perugia.it
Investigator:
Last name:
Giulio Metro
Email:
Principal Investigator
Facility:
Name:
Azienda USL IRCCS di Reggio Emilia
Address:
City:
Reggio Emilia
Zip:
42123
Country:
Italy
Contact:
Last name:
Maria Pagano, MD
Phone:
0039-0522-296602
Email:
maria.pagano@ausl.re.it
Investigator:
Last name:
Maria Pagano
Email:
Principal Investigator
Facility:
Name:
Istituto Nazionale Tumori Regina Elena
Address:
City:
Roma
Zip:
00144
Country:
Italy
Contact:
Last name:
Fabiana L Cecere, MD
Phone:
0039-0652-666030
Email:
fabianaletizia.cecere@ifo.it
Investigator:
Last name:
Fabiana Letizia Cecere
Email:
Principal Investigator
Facility:
Name:
Fondazione Policlinico Universitario A.Gemelli IRCCS - Università Cattolica del Sacro Cuore
Address:
City:
Roma
Zip:
00168
Country:
Italy
Contact:
Last name:
Emilio Bria, MD
Phone:
0039-0630-155202
Email:
emilio.bria@policlinicogemelli.it
Investigator:
Last name:
Emilio Bria
Email:
Principal Investigator
Facility:
Name:
AOU Sassari
Address:
City:
Sassari
Zip:
07100
Country:
Italy
Contact:
Last name:
Antonio Pazzola, MD
Phone:
0039-079-2644622
Email:
antonio.pazzola@aouss.it
Investigator:
Last name:
Antonio Pazzola
Email:
Principal Investigator
Facility:
Name:
Azienda Ospedaliera Santa Maria di Terni
Address:
City:
Terni
Zip:
05100
Country:
Italy
Contact:
Last name:
Sergio Bracarda, MD
Phone:
0039-0744-205410
Email:
s.bracarda@aospterni.it
Investigator:
Last name:
Sergio Bracarda
Email:
Principal Investigator
Facility:
Name:
Azienda Sanitaria Universitaria Friuli Centrale - P.O. Santa Maria della Misericordia
Address:
City:
Udine
Zip:
33100
Country:
Italy
Contact:
Last name:
Marianna Macerelli, MD
Phone:
0039-0432-554586
Email:
marianna.macerelli@asufc.sanita.fvg.it
Investigator:
Last name:
Marianna Macerelli
Email:
Principal Investigator
Facility:
Name:
AOU Integrata di Verona
Address:
City:
Verona
Zip:
37126
Country:
Italy
Contact:
Last name:
Lorenzo Belluomini, MD
Phone:
0039-045-8128127
Email:
lorenzo.belluomini@univr.it
Investigator:
Last name:
Lorenzo Belluomini
Email:
Principal Investigator
Start date:
October 30, 2024
Completion date:
June 1, 2029
Lead sponsor:
Agency:
Gruppo Oncologico Italiano di Ricerca Clinica
Agency class:
Other
Collaborator:
Agency:
Roche Pharma AG
Agency class:
Industry
Source:
Gruppo Oncologico Italiano di Ricerca Clinica
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06663098
