Atezolizumab and Rechallenge Chemotherapy in Relapsed Patients With Extensive-stage Small Cell Lung Cancer (ES-SCLC).

NCT06663098 | Recruiting Phase 2 DMC

• 2 other identifiers: GOIRC-01-20232024-511945-20-00
• Study Type: interventional
• Target: 142
• Locations: 1 country
• Sites: 25

Brief 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.

Conditions

Extensive Stage Small Cell Lung Cancer (ES-SCLC)

Keywords

Extensive-stage small cell lung cancer; atezolizumab

Outcome Measures

Primary Outcomes (1)

• overall survival

  overall survival (OS), defined as the time from the date of registration to the date of death from any cause. Patients still alive at the time of analysis are censored at the last time they are known to be alive.

  through study completion, an average of 1 year

Secondary Outcomes (3)

• frequency of adverse events

  30 days post last dose of study drug

• Progression Free Survival

  through study completion, an average of 6 months

• Objective response rate

  through study completion, an average of 1 year

Study Arms (1)

Arm 1

EXPERIMENTAL

re-challenge chemotherapy plus atezolizumab 1200 mg flat dosing

Drug: Atezolizumab; Drug: Carboplatin; Drug: Etoposide

Interventions

Atezolizumab DRUG

1200 mg IV on day 1 of every 21 days, during induction phase and maintenance phase

Also known as: humanized IgG1 monoclonal antibody against PD-L1

Arm 1

Carboplatin DRUG

AUC 4 or 5, depending on patient's characteristics, on day 1 every 21 days during induction phase

Also known as: re-challenge chemotherapy

Arm 1

Etoposide DRUG

80 mg/sqm or 100 mg/sqm, depending on patient's characteristics, on days 1-2-3 of every 21 days

Also known as: re-challenge chemotherapy

Arm 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of small-cell lung cancer (SCLC) (according to WHO classification 2015) confirmed at pathology (histology or cytology).
• Male or female and ≥ 18 years of age.
• Life expectancy ≥ 12 weeks.
• 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.
• No previous radiotherapy on the only one site disease progression, unless that site had subsequent evidence of progressive disease.
• Eastern Cooperative Oncology Group performance status (ECOG PS) ≤2.
• 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)
• 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.
• 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.
• 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)

You may not qualify if:

• 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 protocol treatment and patients have recovered from AEs related to radiotherapy to \< grade 1
• 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.
• More than 1 line of prior treatment for ES-SCLC.
• First-line treatment without either atezolizumab or durvalumab.
• First-line chemotherapy other than platinum-etoposide.
• Less than 4 cycles of first-line platinum-etoposide.
• 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).
• 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.
• Evidence of leptomeningeal disease.

Sponsors & Collaborators

• Gruppo Oncologico Italiano di Ricerca Clinica: lead
• Roche Pharma AG: collaborator

Study Sites (25)

Centro di Riferimento Oncologico di Aviano (CRO) IRCCS

Aviano (PN), 33081, Italy

NOT YET RECRUITING

IRCCS Istituto Tumori "Giovanni Paolo II"

Bari, 70124, Italy

NOT YET RECRUITING

IRCCS Azienda Ospedaliero_Universitaria di Bologna

Bologna, 40138, Italy

RECRUITING

UOC Medicina Oncologica

Carpi, 41012, Italy

NOT YET RECRUITING

ASST Cremona

Cremona, 26100, Italy

NOT YET RECRUITING

Azienda Ospedaliera S. Croce e Carle di Cuneo

Cuneo, 12100, Italy

NOT YET RECRUITING

AOU Careggi

Florence, 50134, Italy

NOT YET RECRUITING

Azienda USL Toscana nord-ovest Ospedale Versilia

Lido di Camaiore, 55041, Italy

RECRUITING

Azienda USL Toscana Nord Ovest - Ospedale San Luca

Lucca, 55100, Italy

NOT YET RECRUITING

Istituto Scientifico Romagnolo per lo studio e la cura dei Tumori (IRST) "Dino Amadori"

Meldola (FC), 47014, Italy

NOT YET RECRUITING

IRCCS Ospedale San Raffaele

Milan, 20132, Italy

NOT YET RECRUITING

AOU Policlinico di Modena

Modena, 41125, Italy

NOT YET RECRUITING

ASST San Gerardo dei Tintori Foundation

Monza, 20900, Italy

NOT YET RECRUITING

AORN A. Cardarelli

Napoli, 80131, Italy

NOT YET RECRUITING

AOU San Luigi Gonzaga

Orbassano (TO), 10043, Italy

NOT YET RECRUITING

Istituto Oncologico Veneto

Padua, 35128, Italy

NOT YET RECRUITING

UOC di Oncologia Medica

Parma, 43126, Italy

NOT YET RECRUITING

Azienda Ospedaliera Santa Maria della Misericordia

Perugia, 06132, Italy

NOT YET RECRUITING

Azienda USL IRCCS di Reggio Emilia

Reggio Emilia, 42123, Italy

NOT YET RECRUITING

Istituto Nazionale Tumori Regina Elena

Roma, 00144, Italy

NOT YET RECRUITING

Fondazione Policlinico Universitario A.Gemelli IRCCS - Università Cattolica del Sacro Cuore

Roma, 00168, Italy

NOT YET RECRUITING

AOU Sassari

Sassari, 07100, Italy

NOT YET RECRUITING

Azienda Ospedaliera Santa Maria di Terni

Terni, 05100, Italy

NOT YET RECRUITING

Azienda Sanitaria Universitaria Friuli Centrale - P.O. Santa Maria della Misericordia

Udine, 33100, Italy

NOT YET RECRUITING

AOU Integrata di Verona

Verona, 37126, Italy

NOT YET RECRUITING

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• Li L, Liu T, Liu Q, Mu S, Tao H, Yang X, Li Y, Xiong Q, Wang L, Hu Y. Rechallenge of immunotherapy beyond progression in patients with extensive-stage small-cell lung cancer. Front Pharmacol. 2022 Sep 6;13:967559. doi: 10.3389/fphar.2022.967559. eCollection 2022.

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• Spagnolo F, Boutros A, Cecchi F, Croce E, Tanda ET, Queirolo P. Treatment beyond progression with anti-PD-1/PD-L1 based regimens in advanced solid tumors: a systematic review. BMC Cancer. 2021 Apr 17;21(1):425. doi: 10.1186/s12885-021-08165-0.

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• Ardizzoni A, Tiseo M, Boni L. Validation of standard definition of sensitive versus refractory relapsed small cell lung cancer: a pooled analysis of topotecan second-line trials. Eur J Cancer. 2014 Sep;50(13):2211-8. doi: 10.1016/j.ejca.2014.06.002. Epub 2014 Jun 26.

  PMID: 24981975 BACKGROUND

• Baize N, Monnet I, Greillier L, Geier M, Lena H, Janicot H, Vergnenegre A, Crequit J, Lamy R, Auliac JB, Letreut J, Le Caer H, Gervais R, Dansin E, Madroszyk A, Renault PA, Le Garff G, Falchero L, Berard H, Schott R, Saulnier P, Chouaid C; Groupe Francais de Pneumo-Cancerologie 01-13 investigators. Carboplatin plus etoposide versus topotecan as second-line treatment for patients with sensitive relapsed small-cell lung cancer: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2020 Sep;21(9):1224-1233. doi: 10.1016/S1470-2045(20)30461-7.

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• Frampton JE. Atezolizumab: A Review in Extensive-Stage SCLC. Drugs. 2020 Oct;80(15):1587-1594. doi: 10.1007/s40265-020-01398-6.

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• Paz-Ares L, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Ozguroglu M, Ji JH, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Kazarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Shire N, Jiang H, Goldman JW; CASPIAN investigators. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019 Nov 23;394(10212):1929-1939. doi: 10.1016/S0140-6736(19)32222-6. Epub 2019 Oct 4.

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MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

atezolizumab; Carboplatin; Etoposide

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Central Study Contacts

Andrea Ardizzoni, MD

CONTACT

0039-051-2142206; andrea.ardizzoni@aosp-bo.itt

Giuseppe Lamberti, MD

CONTACT

0039-051-2143067; giuseppe.lamberti8@unibo.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2024
• First Posted: October 29, 2024
• Study Start: January 24, 2025
• Primary Completion (Estimated): August 30, 2028
• Study Completion (Estimated): June 1, 2029
• Last Updated: March 13, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (25)