FASTing-like Approach and Maintenance IMMunotherapy in ES-SCLC Patients Not Progressing on Chemoimmunotherapy Induction

NCT05703997 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: INT 207/22
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Cyclic, 5-day calorie restriction is a safe metabolic intervention when combined with standard therapies in cancer patients, favorably reshaping peripheral blood and intratumor metabolism and immunity in a way that may improve the antitumor activity and efficacy of immunotherapy. The goal of this clinical trial is to test if combining cyclic, 5-day calorie restriction with atezolizumab maintenance in patients with ES SCLC achieving at least stable disease after four cycles of induction atezolizumab plus carboplatin and etoposide chemoimmunotherapy may increase the efficacy of a standard first-line, chemo-immunotherapy approach in terms of patient PFS. The main question it aims to answer is: • does the combination of cyclic, 5-day calorie restriction with triweekly atezolizumab increase the 6 months PFS rate, as evaluated from maintenance treatment initiation, compared to historical results with standard atezolizumab maintenance monotherapy in patients with ES SCLC non-progressive after four cycles of first-line chemo-immunotherapy induction with atezolizumab plus carboplatin and etoposide?

Conditions

Small Cell Lung Carcinoma

Keywords

Small Cell Lung Cancer; SCLC; Extensive-stage; Calorie-restriction; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• PFS rate at 6 months

  The percentage of patients not experiencing disease progression or death from any cause after 6 months from experimental maintenance treatment initiation

  6 months from experimental maintenance treatment initiation

Secondary Outcomes (4)

• PFS

  Up to 75 months from experimental maintenance treatment initiation

• OS

  Up to 75 months from experimental maintenance treatment initiation

• Compliance

  Up to 75 months from experimental maintenance treatment initiation

• Adverse events

  Up to 75 months from experimental maintenance treatment initiation

Other Outcomes (4)

• Plasma amino acids

  At the beginning and at the end of the 5-day calorie restriction period of Cycle 1 and Cycle 2 and at the beginning of Cycle 5 and Cycle 8 of the experimental maintenance treatment (each experimental maintenance treatment cycle is 21 days)

• Plasma fatty acids

  At the beginning and at the end of the 5-day calorie restriction period of Cycle 1 and Cycle 2 and at the beginning of Cycle 5 and Cycle 8 of the experimental maintenance treatment (each experimental maintenance treatment cycle is 21 days)

• Serum growth factors

  At the beginning and at the end of the 5-day calorie restriction period of Cycle 1 and Cycle 2 and at the beginning of Cycle 5 and Cycle 8 of the experimental maintenance treatment (each experimental maintenance treatment cycle is 21 days)

Study Arms (1)

Maintenance treatment with cyclic, 5-day calorie restriction plus atezolizumab

EXPERIMENTAL

The experimental maintenance treatment will consist of: * triweekly cycles of 5-day calorie restriction (on days -2 through 2 of each cycle) in combination with * atezolizumab (at a dose of 1200 mg, administered intravenously on day 0 of each cycle) The experimental maintenance treatment will be administered until the occurrence of unacceptable toxic effects, disease progression, consent withdrawal or patient death. Patients interrupting cyclic calorie restriction for any reason other than disease progression may continue the maintenance treatment with atezolizumab alone, if clinically indicated.

Dietary Supplement: Cyclic, 5-day calorie restriction; Drug: Atezolizumab

Interventions

Cyclic, 5-day calorie restriction DIETARY_SUPPLEMENT

Cyclic, 5-day, calorie-restricted (about 600 Kcal on day 1; about 300 Kcal on days 2 to 5), plant-based, low-protein, low-carbohydrate diet.

Maintenance treatment with cyclic, 5-day calorie restriction plus atezolizumab

Atezolizumab DRUG

Atezolizumab 1200 mg administered intravenously.

Maintenance treatment with cyclic, 5-day calorie restriction plus atezolizumab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants who are able to comply with the requirements and restrictions listed in the Informed Consent Form and the study protocol (there is no separate Informed Consent Form for entering the maintenance phase)
• Signature of the informed consent form for those patients who have not previously participated to the induction phase of the study
• Age greater than or equal to 18 years and less than or equal to 75 years
• Willingness and ability to comply with the prescribed cyclic, 5-day calorie restriction regimen, the scheduled visits, treatment plans, laboratory tests and other procedures
• Histologically or cytologically confirmed diagnosis of small-cell lung cancer (SCLC).
• Radiological evidence of extensive-stage (ES) disease.
• Patient has available archival tumor tissue. Patients for whom only cytological material is available may be enrolled only if cytoincluded material is available.
• Patients must have received a first-line, chemoimmunotherapy induction with 4 triweekly cycles of atezolizumab plus carboplatin and etoposide, with the last cycle of induction chemoimmunotherapy administered not more than six weeks before the initiation of experimental maintenance treatment. Delays between cycles of chemoimmunotherapy due to the occurrence of AEs or other medical reasons are considered acceptable, provided that a total number of 4 cycles of chemoimmunotherapy with atezolizumab plus carboplatin and etoposide have been administered, and that there is no radiological evidence of disease progression.
• Radiological evidence of nonprogressive disease after chemoimmunotherapy induction with 4 triweekly cycles of atezolizumab plus carboplatin and etoposide.
• Patients with a history of treated CNS metastases are eligible, if there is no evidence of interim progression between the completion of CNS-directed therapy and the experimental maintenance treatment initiation, and if CNS metastases are asymptomatic.
• An Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
• Presence of an adequate bone marrow and organ function
• Female patients of childbearing potential must agree to abstinence from heterosexual intercourse or to use two highly effective methods of contraception throughout the study and for at least six months after the end of the maintenance treatment.
• Female patients are not of childbearing potential if they meet at least one of the following criteria:
• Have undergone a documented hysterectomy and/or bilateral oophorectomy

You may not qualify if:

• Prior systemic treatment for ES SCLC, with the exception for first-line chemoimmunotherapy induction with 4 triweekly cycles of atezolizumab plus carboplatin and etoposide. Patients who received prior concurrent chemoradiotherapy for limited-stage (LS) disease may be enrolled if concurrent chemoradiotherapy was concluded at least three months before enrollment.
• Patient has not available archival tumor tissue or has only cytological material without cytoincluded material available.
• The patient has not recovered from immune-related AEs of grade 2 or higher from the induction phase with atezolizumab plus carboplatin and etoposide. Patients with adequately-treated, controlled, immune-related skin rash of grade 2 or adequately-treated, controlled, endocrinopathies of grade 2 on replacement therapy can be enrolled.
• Body mass index (BMI) \< 19 kg/m2.
• Unintentional weight loss ≥ 5% in the previous 3 months, unless the patient has a BMI \> 22 kg/m2 and weight loss has been lower than 10% at the time of enrollment in the study; or unintentional weight loss ≥ 10% in the previous 3 months, unless the patient has a BMI \> 25 kg/m2 and weight loss has been lower than 15% at the time of the enrollment in the study. In all cases, weight must have been stable for at least one month before study enrollment.
• Baseline plasma glucose concentration ≤ 60 mg/dL (after at least 8 hours fasting)
• Diagnosis of any other malignancy within 2 years prior to enrollment, with the exception of adequately treated in-situ bladder cancer, in-situ carcinoma of the cervix, uteri, non-melanomatous skin cancer, ductal in-situ breast cancer, thyroid cancer or early-stage prostate cancer (all treatment of which should have been completed at least 6 months prior to enrollment)
• Asymptomatic and untreated, symptomatic or unstable CNS metastases as determined by CT-scan or MRI evaluation during screening and/or prior radiographic assessments.
• Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated but not clinically stable for ≥ 4 weeks prior to the experimental maintenance treatment initiation.
• Leptomeningeal disease.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently).
• History of alcohol abuse.
• Active pregnancy or breastfeeding.
• Known active B or C hepatitis or human immunodeficiency virus (HIV) infection, or occasional finding of active hepatitis B/C infection during screening tests before experimental treatment initiation.
• Serious infections in the previous 4 weeks before the experimental maintenance treatment initiation.

Sponsors & Collaborators

• Fondazione IRCCS Istituto Nazionale dei Tumori, Milano: lead
• IFOM ETS - The AIRC Institute of Molecular Oncology: collaborator
• University of Milan: collaborator

Study Sites (1)

Fondazione IRCCS Istituto Nazionale Tumori

Milan, 20133, Italy

Location

Related Publications (6)

• Rudin CM, Brambilla E, Faivre-Finn C, Sage J. Small-cell lung cancer. Nat Rev Dis Primers. 2021 Jan 14;7(1):3. doi: 10.1038/s41572-020-00235-0.

  PMID: 33446664 BACKGROUND

• Horn L, Mansfield AS, Szczesna A, Havel L, Krzakowski M, Hochmair MJ, Huemer F, Losonczy G, Johnson ML, Nishio M, Reck M, Mok T, Lam S, Shames DS, Liu J, Ding B, Lopez-Chavez A, Kabbinavar F, Lin W, Sandler A, Liu SV; IMpower133 Study Group. First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer. N Engl J Med. 2018 Dec 6;379(23):2220-2229. doi: 10.1056/NEJMoa1809064. Epub 2018 Sep 25.

  PMID: 30280641 BACKGROUND

• Liu SV, Reck M, Mansfield AS, Mok T, Scherpereel A, Reinmuth N, Garassino MC, De Castro Carpeno J, Califano R, Nishio M, Orlandi F, Alatorre-Alexander J, Leal T, Cheng Y, Lee JS, Lam S, McCleland M, Deng Y, Phan S, Horn L. Updated Overall Survival and PD-L1 Subgroup Analysis of Patients With Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide (IMpower133). J Clin Oncol. 2021 Feb 20;39(6):619-630. doi: 10.1200/JCO.20.01055. Epub 2021 Jan 13.

  PMID: 33439693 BACKGROUND

• Ajona D, Ortiz-Espinosa S, Lozano T, Exposito F, Calvo A, Valencia K, Redrado M, Remirez A, Lecanda F, Alignani D, Lasarte JJ, Macaya I, Senent Y, Bertolo C, Sainz C, Gil-Bazo I, Eguren-Santamaria I, Lopez-Picazo JM, Gonzalez A, Perez-Gracia JL, de Andrea CE, Vicent S, Sanmamed MF, Montuenga LM, Pio R. Short-term starvation reduces IGF-1 levels to sensitize lung tumors to PD-1 immune checkpoint blockade. Nat Cancer. 2020 Jan;1(1):75-85. doi: 10.1038/s43018-019-0007-9. Epub 2020 Jan 13.

  PMID: 35121837 BACKGROUND

• Vernieri C, Fuca G, Ligorio F, Huber V, Vingiani A, Iannelli F, Raimondi A, Rinchai D, Frige G, Belfiore A, Lalli L, Chiodoni C, Cancila V, Zanardi F, Ajazi A, Cortellino S, Vallacchi V, Squarcina P, Cova A, Pesce S, Frati P, Mall R, Corsetto PA, Rizzo AM, Ferraris C, Folli S, Garassino MC, Capri G, Bianchi G, Colombo MP, Minucci S, Foiani M, Longo VD, Apolone G, Torri V, Pruneri G, Bedognetti D, Rivoltini L, de Braud F. Fasting-Mimicking Diet Is Safe and Reshapes Metabolism and Antitumor Immunity in Patients with Cancer. Cancer Discov. 2022 Jan;12(1):90-107. doi: 10.1158/2159-8290.CD-21-0030. Epub 2021 Nov 17.

  PMID: 34789537 BACKGROUND

• Ligorio F, Fuca G, Provenzano L, Lobefaro R, Zanenga L, Vingiani A, Belfiore A, Lorenzoni A, Alessi A, Pruneri G, de Braud F, Vernieri C. Exceptional tumour responses to fasting-mimicking diet combined with standard anticancer therapies: A sub-analysis of the NCT03340935 trial. Eur J Cancer. 2022 Sep;172:300-310. doi: 10.1016/j.ejca.2022.05.046. Epub 2022 Jul 8.

  PMID: 35810555 BACKGROUND

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

atezolizumab

Condition Hierarchy (Ancestors)

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

Study Officials

• Filippo de Braud, MD

  Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Claudio Vernieri, MD, PhD

CONTACT

(+39) 02 2390 3066; claudio.vernieri@istitutotumori.mi.it

Giovanni Fucà, MD

CONTACT

(+39) 02 2390 3066; giovanni.fuca@istitutotumori.mi.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: December 13, 2022
• First Posted: January 30, 2023
• Study Start: January 1, 2023
• Primary Completion: January 1, 2025
• Study Completion (Estimated): January 1, 2029
• Last Updated: January 30, 2023

Record last verified: 2022-12

Locations

IT (1)