Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05384015
Other study ID # GECP 20/06_PEERS
Secondary ID 2020-005230-15
Status Recruiting
Phase Phase 2
First received
Last updated
Start date November 7, 2022
Est. completion date July 30, 2027

Study information

Verified date February 2024
Source Fundación GECP
Contact Eva Pereira
Phone +34934302006
Email gecp@gecp.org
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This is a multicenter, open-label, non-randomized, single arm, 2 parts, phase II clinical trial evaluating the efficacy and safety of pembrolizumab and lenvatinib plus standard of care chemotherapy (with carboplatin and etoposide ) in subjects with histologically confirmed extensive-stage small-cell lung cancer who have not previously received systemic therapy for this malignancy.


Description:

A total of 85 subjects will be assigned to study treatment with pembrolizumab + lenvatinib + chemotherapy. Positive tumor programmed cell death-ligand 1 (PD-L1) expression will not be required for enrollment; however, subjects' tumors will be screened for PD-L1 expression. The primary endpoint for the Part 1 is to determine the safety of the combination. The primary endpoint for Part 2 is to determine the Progression Free survival (PFS) using RECIST 1.1. assessed by investigator. The sponsor estimates that the trial will require approximately 4 years from the time the first participant signs the informed consent until the last participant's last study-related telephone call or visit (2 years recruiting patients, 1 year of treatment and at least 1 year of follow up)


Recruitment information / eligibility

Status Recruiting
Enrollment 85
Est. completion date July 30, 2027
Est. primary completion date July 30, 2026
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - 1. Histologically or cytologically documented new diagnosis of SCLC by histology or cytology from brushing, washing, or needle aspiration. Note: Subjects who do not have histology samples (defined as core or excisional biopsy, or resections) will need to undergo a new biopsy to provide a tissue sample. Mixed tumors are not eligible. - 2. ES-SCLC, stage IV disease by the American Joint Committee on Cancer, 8th Edition criteria (70), [T any, N any, M1a, M1b, M1c], or T3-4 due to multiple lung nodules that are too extensive or tumor/nodal volume that is too large to be encompassed in a tolerable radiation plan. - 3. Have at least one lesion that meets criteria for being measurable, as defined by RECIST 1.1. - 4. Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated for biomarker assessment. - 5. Be male or female =18 years of age inclusive, on the day of signing informed consent. - 6. Have a life expectancy of at least 3 months from the study start. - 7. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 7 days prior to the first dose of study intervention. - 8. Male participants are eligible to participate if they agree to the following during the intervention period and for at least 30 days after the last dose of lenvatinib placebo and up to 180 days after the last dose of chemotherapeutic agents: - Refrain from donating sperm PLUS either: - Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR - Must agree to use contraception unless confirmed to be azoospermic. - 9. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: - Is not a WOCBP OR - Is a WOCBP and using a contraceptive method that is highly effective - 10. Have voluntarily agreed to participate by giving written consent for the study prior to any specific protocol procedures. - 11. Have adequate organ function Exclusion Criteria: - 1. Has received any prior therapy (chemotherapy, radiotherapy, surgical resection) or other investigational agent for the treatment of SCLC. - 2. Is expected to require any other form of antineoplastic therapy for SCLC, including radiation therapy while on study. - 3. Active CNS metastases and/or carcinomatous meningitis as determined per CT or MRI during screening. Participants with previously treated brain metastases (eg, whole brain radiation treatment [WBRT], stereotactic radiosurgery, or equivalent) may participate only if they satisfy the following: - Completed treatment at least 14 days prior to the first dose of study intervention. - Are clinically stable, without requirement of steroid treatment for at least 7 days prior to first dose of study intervention. - Are radiologically stable. - Patients with new asymptomatic CNS metastases detected at the screening scan must receive radiation therapy and/or surgery for CNS metastases. Following treatment, these patients may then be eligible without the need for an additional brain scan prior to enrollment, if all other criteria are met. - 4. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137). - 5. Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for = 1 week prior to enrollment. - 6. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). A subject who is clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible. - 7. .Has known history of, or active, neurologic paraneoplastic syndrome of autoimmune nature. - 8. Radiographic evidence of intratumoral cavitations, encasement, or invasion of a major blood vessel. Additionally, the degree of proximity to major blood vessels should be considered for exclusion because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis after lenvatinib therapy. - 9. Has had major surgery within 4 weeks prior to first dose of study interventions. - 10. Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of trial drug. - 11. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention. - 12. Has an active autoimmune disease or inflammatory disorder that has required systemic treatment in the past 2 years. - 13. Has a diagnosis of immunodeficiency or is taking chronic systemic steroid therapy (in dosing of >10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. - 14. Has known history of a second malignancy other than SCLC, unless potentially curative treatment has been completed with no evidence of malignancy for at least 3 years since the initiation of that therapy. - 15. Poor controlled hypertension (BP>150/90 mmHg) despite appropriate treatment. - 16. Participants with proteinuria >1+ on urine dipstick testing/urinalysis will undergo 24-hour urine collection for quantitative assessment of proteinuria. Participants with urine protein =1 g/24 hours will be ineligible. - 17. Has a prolongation of QTc interval (calculated using Fridericia's formula) of >480 msec. - 18. Has a known history of interstitial lung disease, idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan - 19. Uncontrolled intercurrent active infection at the time of enrollment requiring systemic therapy. - 20. Has a known history of Human Immunodeficiency Virus (HIV) infection. - 21. Has a known history of Hepatitis B or known active Hepatitis C. - 22. Has a known history of active tuberculosis. - 23. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study. - 24. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. - 25. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study. - 26. Prior allogeneic bone marrow transplantation or solid organ transplant. - 27. Any gastrointestinal condition that would affect the absorption of Lenvatinib. - 28. Has active hemoptysis or major arterial thromboembolic event within 2 weeks prior to the first dose of study intervention. - 29. Has significant cardiovascular impairment within 12 months prior to the first dose of study intervention. - 30. Has a history of a severe (Grade = 3) hypersensitivity reaction to treatment with another monoclonal antibody or has a known hypersensitivity to lenvatinib, pembrolizumab, carboplatin or etoposide and/or any of its excipients. - 31. Has a clinically active diverticulitis, inflammatory bowel disease, intra-abdominal abscess, gastrointestinal obstruction and/or abdominal carcinomatosis. - 32. Has a history of a gastrointestinal perforation within 6 months before the first dose of study intervention. - 33. Has preexisting Grade = 3 gastrointestinal or non-gastrointestinal fistula. - 34. Has serious nonhealing wound, ulcer, or bone fracture within 28 days before first dose of study intervention. - 35. Has any major hemorrhage or venous thromboembolic events within 3 months before the first dose of study intervention. - 36. Poor medical risk due to a serious, uncontrolled medical disorder or nonmalignant systemic disease.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Lenvatinib
Lenvatinib is an oral, potent multiple receptor tyrosine kinase (RTK) i that selectively inhibits VEGF-driven VEGFR2 phosphorylation and suppressed proliferation and tube formation in human umbilical vein endothelial cell models. Antitumor activity of lenvatinib in vivo has been shown in numerous xenograft animals. These results suggest that lenvatinib may be a novel anticancer therapy through inhibition of angiogenesis and may be useful as either monotherapy or in combination with other anticancer drugs. Part 1 (safety run-in) and Part 2: The study intervention consists of: Dose: 8 mg (induction) and 20 mg (maintenance) Dose Frequency: Once daily Dose formulation: Capsule Route of administration: Oral Treatment duration: 4 cycles (induction) and no treatment duration limit (maintenance).
Pembrolizumab
Pembrolizumab is a potent humanized immunoglobulin G4 (IgG4) monoclonal antibody (mAb) with high specificity of binding to the programmed cell death 1 (PD-1) receptor, thus inhibiting its interaction with programmed cell death ligand 1 (PD-L1) and programmed cell death ligand 2 (PD-L2). Part 1 (safety run-in) and Part 2: Dose: 200 mg Frequency: Day 1, Q3W Route: Intravenous Treatment Period: Up to 35 cycles or until reaching a discontinuation criterion
Etoposide
Standard first-line treatment for the vast majority of patients with SCLC, regardless of stage, involves combination chemotherapy with etoposide plus cisplatin or carboplatin. Pharmacotherapeutic group: Cytostatics, plant alkaloids and other natural products, derived from podophyllotoxin. Mechanism of action :The main effect of etoposide appears to be in the late S and early G2 phase of the cell cycle, in mammalian cells. Part 1 (safety run-in) and Part 2: Dose: 100 mg/m2 Frequency: Day 1-3, Q3W Route: Intravenous Treatment Period: 4 cycles
Carboplatin
Pharmacotherapeutic group: Other antineoplastic agents, platinum compounds. Carboplatin, like cisplatin, binds to DNA to produce inter- and intra-strand cross-links cells exposed to carboplatin. DNA reactivity has been linked to cytotoxicity. Part 1 (safety run-in) and Part 2: Dose: AUC5 Frequency: Day 1, Q3W Route: Intravenous Treatment Period: 4 cycles

Locations

Country Name City State
Spain Hospitalario Universitario A Coruña A Coruña La Coruña
Spain Hospital General Universitario de Alicante Alicante
Spain ICO Badalona, Hospital Germans Trias i Pujol Badalona Barcelona
Spain Hospital Clínic De Barcelona Barcelona
Spain Hospital de la Santa Creu i Sant Pau Barcelona
Spain Hospital Parc Taulí Barcelona
Spain Hospital Universitari Vall d' Hebron Barcelona
Spain Hospital De Basurto Bilbao
Spain ICO Girona, Hospital Josep Trueta Girona
Spain Hospital Universitario Lucus Augusti Lugo
Spain Hospital 12 De Octubre Madrid
Spain Hospital Universitario Fundación Jiménez Díaz Madrid
Spain Hospital Universitario Puerta de Hierro Majadahonda Madrid
Spain Hospital Universitario Regional de Málaga Málaga
Spain Hospital Son Espases Palma De Mallorca
Spain Complejo Hospitalario de Navarra Pamplona
Spain Hospital Clínico de Valencia Valencia
Spain Hospital General Universitario de Valencia Valencia

Sponsors (1)

Lead Sponsor Collaborator
Fundación GECP

Country where clinical trial is conducted

Spain, 

Outcome

Type Measure Description Time frame Safety issue
Primary Part 1: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) of lenvatinib 8 mg to be used in combination with pembrolizumab plus chemotherapy Occurrence and severity of adverse events, with severity determined by NCI CTCAE v5.0 criteria. From the subject's written consent to participate in the study through 90 days after the final administration of the drug
Primary Part 2:To assess the efficacy of the treatment in terms of the Progression Free Survival (PFS) PFS is defined as the time from enrollment to the date of the first documentation of disease progression, as determined by investigator per RECIST 1.1, or death from any cause, whichever is earlier. From the date of the end of induction treatment until 12 months
Secondary Part 1 (for patients treated at part 2): Objective response per RECIST 1.1 based on investigator Objective response is a confirmed complete response (CR) or partial response (PR), as determined by investigator per RECIST 1.1. From the date of the end of treatment until 12 months
Secondary Part 1 (for patients treated at part 2): Duration of Response (DOR) per RECIST 1.1 based on investigator DOR is defined as the time from the first documented evidence of CR or PR until disease progression or death due to any cause (whichever is earlier), for participants who demonstrate a confirmed CR or PR. Response will be determined by BICR per RECIST 1.1. From date of documentation of tumor response until date of first documented progression, assessed up to 12 months
Secondary Part 1 (for patients treated at part 2): Overall Survival OS is defined as the time from enrollment to the date of death from any cause. From the date of the end of treatment until 12 months
Secondary Part 2: Objective response per RECIST 1.1 based on investigator Objective response is a confirmed complete response (CR) or partial response (PR), as determined by investigator per RECIST 1.1. From the date of the end of treatment until 12 months
Secondary Part 2: Duration of Response (DOR) per RECIST 1.1 based on investigator DOR is defined as the time from the first documented evidence of CR or PR until disease progression or death due to any cause (whichever is earlier), for participants who demonstrate a confirmed CR or PR. Response will be determined by BICR per RECIST 1.1. From date of documentation of tumor response until date of first documented progression, assessed up to 12 months
Secondary Part 2:Overall Survival OS is defined as the time from enrollment to the date of death from any cause. From the date of the end of treatment until 12 months
Secondary Part 2: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) of treatment Occurrence and severity of adverse events, with severity determined by NCI CTCAE v5.0 From the subject's written consent to participate in the study through 90 days after the final administration of the drug
See also
  Status Clinical Trial Phase
Not yet recruiting NCT02179528 - Study of Small Doses of Etoposide as Maintenance Treatment in Small Cell Lung Cancer(SCLC) Phase 2
Recruiting NCT06030258 - IN10018 Combination Therapy in Treatment-naïve ES-SCLC Phase 1/Phase 2
Not yet recruiting NCT05745350 - First Line Pembrolizumab, Plinabulin Plus Etoposide and Platinum (EP) for ES-SCLC Phase 2
Completed NCT03325816 - Nivolumab and 177Lu-DOTA0-Tyr3-Octreotate for Patients With Extensive-Stage Small Cell Lung Cancer Phase 1/Phase 2
Recruiting NCT05856695 - A Phase II Study Assessing the Efficacy of Etoposide Free Chemotherapy Plus Durvalumab (MEDI4736) in First Line Extensive Disease Small Cell Lung Cancer (SCLC) Phase 2
Recruiting NCT05703971 - Quaratusugene Ozeplasmid (Reqorsa) and Atezolizumab Maintenance Therapy in ES-SCLC Patients Phase 1/Phase 2
Not yet recruiting NCT06429696 - PD-L1 Inhibitor Combined With Apatinib as First-line Maintenance Treatment for Extensive-stage Small Cell Lung Cancer Phase 2
Terminated NCT00003496 - Antineoplaston Therapy in Treating Patients With Recurrent or Extensive-Stage Small Cell Lung Cancer Phase 2
Completed NCT03059667 - Immunotherapy as Second-line in Patient With Small Cell Lung Cancer Phase 2
Active, not recruiting NCT03923270 - Radiotherapy and Durvalumab/Durvalumab Combo (Tremelimumab/Olaparid) for Small Cell Lung Cancer Phase 1
Not yet recruiting NCT06348797 - Phase I Clinical Study of α-PD-L1/DLL3 CAR-T in Patients With R/R SCLC Phase 1
Active, not recruiting NCT04462276 - Thoracic RadiothErapy With Atezolizumab in Small Cell lUng canceR Extensive Disease Phase 2
Recruiting NCT05680922 - DLL3-Directed Chimeric Antigen Receptor T-cells in Subjects With Extensive Stage Small Cell Lung Cancer Phase 1
Not yet recruiting NCT04967625 - A Phase II Study of Sintilimab Combined With Anlotinib in Treatment of ED-SCLC Phase 2
Recruiting NCT04659785 - A Study of Fluzoparib Combined With Apatinib as Second-Line Treatment of Patients With Extensive Stage Small Cell Lung Cancer(FA-ES-SCLC) Phase 1/Phase 2
Active, not recruiting NCT04670445 - Improving Patient and Caregiver Understanding of Risks and Benefits of Immunotherapy for Advanced Cancer N/A
Not yet recruiting NCT05066945 - Application of ctDNA in the Evaluation of Curative Effect and Prognosis of SCLC Patients
Recruiting NCT05945745 - Molecular Analysis and Treatment Options of SCLC
Not yet recruiting NCT03755115 - SHR-1210 Combined With Epirubicin in the Treatment of Extensive Disease Small Cell Lung Cancer Phase 2
Terminated NCT05027867 - KRT-232 in Subjects With Relapsed or Refractory Small Cell Lung Cancer Phase 2