Patients With ES-SCLC and ECOG PS=2 Receiving Atezolizumab-Carboplatin-Etoposide (SPACE)
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|ClinicalTrials.gov Identifier: NCT04221529|
Recruitment Status : Recruiting
First Posted : January 9, 2020
Last Update Posted : January 13, 2020
Small cell lung cancer (SCLC) is a rapidly proliferating, neuroendocrine tumor that accounts for about 15% of all lung cancers. Most patients have metastases at primary diagnosis involving sites like bone, adrenal glands, liver and brain.
Compared with non-small-cell lung cancer (NSCLC) SCLC has a unique natural history with a shorter doubling time, higher growth fraction, earlier development of widespread metastases, and uniform initial response to chemo- or radiotherapy.
The combination of cis- or carboplatin and etoposide is the standard of care in the first-line treatment of stage IV (extensive-disease) SCLC (ED-SCLC). Despite response rates of 50-80%, most patients relapse within six months and the median survival time is less than 10 months. Between 14 and 23% of SCLC patients develop brain metastases.
New cytotoxic agents as well as targeted therapies have not been able to show any improvement of survival in this group of patients.
Early phase trials of PD 1/PD L1-blocking immunotherapeutic agents in patients with recurrent or ED SCLC have shown promising response rates and good tolerability. Immunotherapy may also contribute to the efficacy of systemic treatment by maintaining initial responses to chemotherapy. A double-blind, placebo-controlled phase 3 trial indicates that the addition of atezolizumab to standard chemotherapy significantly improves overall survival and progression-free survival compared with chemotherapy alone in treatment-naïve patients with ED-SCLC who are in good general condition (ECOG 0 or 1). However, about one in three SCLC patients has a poor performance status (ECOG≥2), which is associated with even shorter survival times of under eight months. At present, there is little information regarding the feasibility, safety and efficacy of adding atezolizumab to standard chemotherapy for this considerable fraction of patients.
The investigators expect, that atezolizumab in addition to chemotherapy is feasible in patients with stage IV SCLC and reduced performance status and therefore crucial efficacy data can be acquired in this trial to evaluate a putative Phase III transition in this particular patient population.
|Condition or disease||Intervention/treatment||Phase|
|SCLC, Extensive Stage||Drug: Atezolizumab||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||70 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Single-Arm Phase II-Study in Patients With Extensive Stage Small Cell Lung Cancer (ES-SCLC) With Poor Performance Status Receiving Atezolizumab-Carboplatin-Etoposide|
|Actual Study Start Date :||January 6, 2020|
|Estimated Primary Completion Date :||December 2023|
|Estimated Study Completion Date :||June 2024|
Four 21-day cycles of induction therapy with atezolizumab+carboplatin+etoposide followed by 21-day cycles of maintenance therapy with atezolizumab.
1200 mg i.v. on day 1 of each cycle
- Overall survival (OS) [ Time Frame: Measured from first dose of experimental IMP (or first dose of chemotherapy, whichever occurs first) through study completion, an average of one year. ]OS is defined as the length of time from first dose of experimental IMP (or first dose of chemotherapy, whichever occurs first) to the date of death. A subject who has not died will be censored at last known date alive.
- Objective response rate (ORR) (RECIST 1.1) [ Time Frame: Starting from Screening up to an average of one year. ]ORR is defined as the proportion of All Treated Subjects whose best overall response (BOR) from baseline is either a CR or PR per RECIST 1.1 criteria. BOR is determined by the best response designation recorded between the base-line assessment (must precede the date of first dose of IMP) and the date of objectively documented progression. For subjects without documented progression, all available response designations will contribute to the BOR determination. Among All Treated Subjects the ORR (based on investigator assessments according to RECIST 1.1) will be summarized by binomial response rates and their corresponding two-sided 95% exact CIs using Clopper-Pearson method.
- Progression-free suvival (PFS) [ Time Frame: Starting from Screening up to an average of one year. ]PFS is defined as the time from first dose of IMP to the date of the first documented tumor progression, based on investigator assessments (per RECIST 1.1), or death due to any cause.
- Incidence of Treatment-Emergent adverse events, serious adverse events and laboratory abnormalities leading to treatment discontinuation [ Time Frame: Starting from Screening up to an average of one year. ]The incidence of treatment-emergent adverse events, serious adverse events and laboratory abnormalities leading to treatment discontinuation will be used as an indicator for safety and tolerability of the IMP. Toxicities in these incidents will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
- Quality of life (EORTC-QLQ-C30) [ Time Frame: Starting from Screening up to an average of one year. ]
QoL questionnaires (EORTC-QLQ-C30, i.e. European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire with 30 questions for patients with cancer) will be analyzed according to the respective recommendations and manuals (scoring and interpretation materials) issued by the creators of the instruments.
Patients have to answer 28 questions from "not at all" (1) to "very much" (4), where lower scores mean a better outcome. The last two questions range from "very poor" (1) to "excellent" (7), where higher scores mean a better outcome.
- Quality of life (PRO-CTCAE) [ Time Frame: Starting from Screening up to an average of one year. ]
QoL questionnaires (PRO-CTCAE, i.e. Patient Reported Outcome - Common Terminology Criteria for Adverse Events) will be analyzed according to the respective recommendations and manuals (scoring and interpretation materials) issued by the creators of the instruments.
Patients have to answer 22 questions either ranging from "none", "mild", "moderate", "severe" to "very severe" or from "not at all", "a little bit", "somewhat", "quite a bit" to "very much". Lower values mean a better outcome.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04221529
|Contact: Tim Overkamp, Dr.||+49 30 8145 344 firstname.lastname@example.org|
|Contact: Katrin Krause||+49 30 8145 344 email@example.com|
|Klinikum Esslingen GmbH||Recruiting|
|Esslingen, Germany, 73730|
|Contact: Martin Faehling, M.D. +49 0711 3103 ext 2402 firstname.lastname@example.org|
|Principal Investigator:||Martin Reck, Prof. Dr.||LungenClinic Grosshansdorf|