Efficacy and Safety Study of a New Therapeutic Strategy in the Treatment of Extended-Disease Small-Cell Lung Cancer

NCT04730999 | Completed Phase 2

• 2 other identifiers: GOIRC-01-20192019-003798-25
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 14

Brief Summary

Small cell lung cancer (SCLC) is an aggressive type of neuroendocrine tumor with the majority of patients (about 60-70%) being diagnosed with metastatic disease and with a median survival ranging from 7 to 12 months. Combination chemotherapy (CT), namely a platinum and etoposide-based regimen, represents the cornerstone of treatment for extended disease (ED) SCLC. Despite this the duration of response is short and nearly all patients develop disease relapse or progression. The recent approval of atezolizumab in combination with carboplatin and etoposide as first line in patients with ED SCLC is surely a step forward in the understanding the molecular landscape and treatment of this complex tumor, but new therapeutic approaches need to be explored. This trial aims to assess the efficacy in terms of 1 year survival a new therapeutic strategy that combines to the standard CT (carboplatin and etoposide), two drugs indicated in the tratment of several types of tumors: bevacizumab and atezolizomab. The treatment will start with an induction phase during which eligible patients will receive, by intravenous way, a combination of the above mentioned drugs according to a specific administration regimen. This phase will last about 18 weeks. Therafter the treatment will proceed with a maintenence phase lasting for a maximum of 54 weeks during which the patients will receive only atezolizumab and bevacizumab, by intravenous way, according to a specific administration regimen. Treatment will be discontnued in case of disease progression, unacceptable toxicity, patient refusal or loss of clinical benefit (for atezolizumab). During the study period the patients will undergo to periodic visits and laboratory, radiologic assessments to monitor the efficacy and the safety of the ongoing treatment.

Conditions

Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Percentage of patients surviving 1 year after study treatment end

  Interval between the date of enrolment and the date of death from any cause, up to a maximum of 25 months.

Secondary Outcomes (3)

• Incidence and severity of Treatment-Emergent Adverse Events [Safety and Tolerability]

  Interval between the date of enrolment and the date of death from any cause, up to a maximum of 15 months

• Overall Response Rate (ORR)

  Interval between the date of enrolment and the date of death from any cause, up to a maximum of 13 months.

• Progression-Free Survival (PFS)

  Interval between the date of enrolment and the date of progressive disease, or death, up to a maximum of 13 months.

Study Arms (1)

Single Arm

EXPERIMENTAL

Induction phase (6 cycles, 21 days duration): carboplatin, etoposide, bevacizumab and atezolizumab. Maintenance phase (12 cycles, 21 days duration): bevacizumab and atezolizumab

Drug: Etoposide; Drug: Carboplatin; Drug: Bevacizumab; Drug: Atezolizumab

Interventions

Etoposide DRUG

Induction phase: 100 mg/sqm on days 1-3, for a maximum of 6 cycles (each one of 21 days duration). Intravenous administration. Treatment will continue until progression of disease, unacceptable toxicity, patient refusal.

Single Arm

Carboplatin DRUG

Induction phase: AUC 5 on day 1 for a maximum of 6 cycles (each one of 21 days duration). Intravenous administration. Treatment will continue until progression of disease, unacceptable toxicity, patient refusal.

Single Arm

Bevacizumab DRUG

Induction phase: 7.5 mg/kg on day 1, for a maximum of 6 cycles (each one of 21 days duration). Intravenous administration. Maintenance phase: 7.5 mg/kg on day 1, for a maximum of 12 cycles (each one of 21 days duration). Intravenous administration. In both phases, the treatment will continue until progression of disease, unacceptable toxicity, patient refusal.

Single Arm

Atezolizumab DRUG

Induction phase: flat dosing of 1200 mg on day 1, for a maximum of 6 cycles ( each one of 21 days duration). Intravenous administration. Maintenance phase: flat dosing of 1200 mg on day 1, for a maximum of 12 cycles (each one of 21 days duration). Intravenous administration. In both phases, the treatment will continue until progression of disease, unacceptable toxicity, patient refusal, loss of clinical benefit.

Single Arm

Eligibility Criteria

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

You may qualify if:

• Histologically or cytological documented small cell lung cancer (SCLC) or poorly differentiated (G3) neuroendocrine carcinoma of the lung
• Extensive stage disease (disease which cannot be encompassed in a single radiation portal including pleural dissemination and supraclavicular node metastasis)
• No prior chemotherapy or treatment with another systemic anti-cancer agent (Note: Patients who have received prior chemoradiotherapy for limited-stage SCLC must have been treated with curative intent and experienced a treatment-free interval of at least 6 months since last chemotherapy, radiotherapy or chemoradiotherapy cycle from diagnosis of extended-disease SCLC)
• No need for concomitant chest irradiation
• Males or females, age ≥18 years
• ECOG performance status 0-1
• Life expectancy \> 12 weeks
• Adequate hepatic and renal functions \[i.e. total bilirubin \< 1.5 times the ULN; - AST and ALT \< 3.0 times the ULN (AST and ALT \< 5.0 x ULN is acceptable if the liver has tumor involvement); Albumin≥ 25 g/L (2.5 g/dL); serum creatinine ≤1.5 times the ULN or creatinine clearance, calculated according to the formula of Cockcroft and Gault \> 60 ml/min; urine dipstick for proteinuria \<2+. If urine dipstick is \>2+, 24-hour urine must demonstrate ≤ 1 g of protein in 24 hours\]
• Adequate hematologic function, as evidenced by an absolute neutrophil count (ANC) ≥1500/µL, hemoglobin ≥9 g/dL (5.58 mmol/L), and platelets ≥100,000/µL.
• Adequate coagulation function as defined by International Normalized Ratio (INR) ≤1.5 and a partial thromboplastin time (PTT) (PTT/aPTT) ≤ 1.5 x upper limits of normal \[ULN\]. Patients on full-dose anticoagulation must be on a stable dose (minimum duration 14 days) of oral anticoagulant or low molecular weight heparin (LMWH). If receiving warfarin, the patient must have an INR ≤3.0. For heparin and LMWH there should be no active bleeding (that is, no bleeding within 14 days prior to first dose of protocol therapy) or pathological condition present that carries a high risk of bleeding (for example, tumor involving major vessels or known varices).
• Negative HIV test at screening with respect of any applicable law and the indication of Atezolizumab use.
• Negative total hepatitis B core antibody (HBcAb) test at screening, or positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening. Please note: The HBV DNA test will be performed only for patients who have a positive total HBcAb test
• Negative hepatitis C virus (HCV) antibody test at screening.
• Female patients of childbearing potential must have a negative serum pregnancy test within 72 hours prior to first dose of protocol therapy.
• Male patients who are sexually active must use effective contraception during treatment with chemotherapy and for at least 6 months after the final dose of chemotherapy to avoid exposing the embryo. Men must refrain from donating sperm during this same period.

You may not qualify if:

• The patient has experienced any Grade 3-4 gastrointestinal bleeding within 3 months prior to first dose of protocol therapy.
• The patient has a history of deep vein thrombosis (DVT), pulmonary embolism (PE), or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered "significant") during the 3 months prior to first dose of protocol therapy.
• Symptomatic brain metastases or spinal cord compression (CT or MRI of the head is required within 4 weeks prior to registration) requiring immediate radiotherapy for palliation. Asymptomatic patients with treated or untreated CNS lesions are eligible, provided that all of the following criteria are met:
• A. Presence outside the CNS of measurable disease per RECIST v1.1 B. No history of intracranial hemorrhage, spinal cord hemorrhage or heorrhagic intracranial lesions C. No stereotactic radiotherapy or whole brain radiotherapy within 14 days prior to initiation of study treatment or neurosurgical resection within 28 days prior to initiation of study treatment D. Concurrent therapy of corticosteroids ≤ 10 mg of oral prednisone or equivalent and/or anticonvulsant therapy at a stable dose E. Metastases are limited to the cerebellum or the supratentorial region (i.e., no metastases to the midbrain, pons, medulla or spinal cord) F. No evidence of interim progression between completion of CNS directed therapy (if administered) and initiation of study treatment
• History of leptomeningeal disease
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) Patients with indwelling catheters (e.g., Pleurocath) are allowed.
• Uncontrolled or symptomatic hypercalcemia (ionized calcium \> 1.5 mmol/L, calcium \> 12 mg/dL or corrected calcium \> ULN)
• Active tubercolosis
• Significant traumatic injury or radiotherapy involving an extensive field within the last 4 weeks prior to first dose of study treatment or anticipation of the need for major surgery during study treatment. Palliative radiotherapy to a limited field is allowed if concluded at least 2 weeks prior enrolment.
• The patient experienced hemoptysis (defined ≥ one-half teaspoon of bright red blood per episode) within 2 months prior to first dose of protocol therapy or with radiographic evidence of intratumor cavitation.
• Other malignancies (previous or current), except for adequately treated in situ carcinoma of the uterine cervix, basal or squamous cell carcinoma of the skin, localized prostate cancer surgically treated with curative intent or ductal carcinoma in situ treated surgically treated with curative intent or if previous malignancy was more than 5 years prior and there are no signs or symptoms of recurrence
• The patient has experienced any arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to first dose of protocol therapy.
• The patient has uncontrolled or poorly-controlled hypertension (\>150 mmHg systolic or \> 100 mmHg diastolic for \>4 weeks) despite standard medical management. Anti-hypertensive therapy to achieve these parameters is allowable.
• Prior history of hypertensive crisis or hypertensive encephalopathy
• Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to registration

Sponsors & Collaborators

• Gruppo Oncologico Italiano di Ricerca Clinica: lead
• Roche Pharma, Italy: collaborator
• YGHEA, CRO Division of Ecol Studio spa: collaborator
• Dr. Luca Boni U.O. Epidemiologia Clinica, IRCCS Ospedale Policlinico San Martino - IST NORD CBA: collaborator

Study Sites (14)

UOC di Oncologia Medica - AOU Policlinico S. Orsola Malpighi

Bologna, 40138, Italy

Location

UOC Oncologia Medica - PO A.Perino - ASL di Brindisi

Brindisi, 72100, Italy

Location

UOC Medicina Oncologica - Ospedale di Carpi - Azienda USL di Modena

Carpi, 41012, Italy

Location

UO di Oncologia - Istituti Ospitalieri di Cremona - ASST Di Cremona

Cremona, 26100, Italy

Location

UOC Oncologia Medica - AO S. Croce e Carle di Cuneo

Cuneo, 12100, Italy

Location

UOC di Oncologia Ematologia - AOU di Ferrara

Ferrara, 44124, Italy

Location

UOC Oncologia Medica 1 - AOU Careggi

Florence, 50134, Italy

Location

Oncologia medica - Policlinico San Martino

Genova, 16132, Italy

Location

UOC Oncologia Medica - Azienda ULSS9 Veneto

Legnago, 37045, Italy

Location

Dip. Oncologia-Ematologia - UO Oncologia - AOU Policlinico di Modena

Modena, 41124, Italy

Location

UOC Oncologia Medica - AORN "A. Cardarelli"

Napoli, 80131, Italy

Location

Istituto Oncologico Veneto IRCCS

Padua, 35128, Italy

Location

UOC di Oncologia Medica - AOU di Parma

Parma, 43126, Italy

Location

Dipartimento di Oncologia ASUIUD

Udine, 33100, Italy

Location

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MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

Etoposide; Carboplatin; Bevacizumab; atezolizumab

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)

Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Coordination Complexes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Andrea Ardizzoni, Dr

  S. Orsola-Malpighi University Hospital - Dept. Oncology-Haematology

  PRINCIPAL INVESTIGATOR

• Karim Rihawi, Dr

  S. Orsola-Malpighi University Hospital - Dept. Oncology-Haematology

  STUDY CHAIR

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: December 21, 2020
• First Posted: January 29, 2021
• Study Start: July 1, 2020
• Primary Completion: June 1, 2023
• Study Completion: June 19, 2024
• Last Updated: July 5, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

IT (14)