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Immunotherapy in Combination With Chemotherapy in Small-cell Lung Cancer (PAVE)

Primary Purpose

Small Cell Lung Carcinoma

Status

Active

Phase

Phase 2

Locations

Greece

Study Type

Interventional

Intervention

Avelumab

About this trial

This is an interventional treatment trial for Small Cell Lung Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Signed written informed consent
Male or female patients aged more than or equal to (≥) 18 years
With Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1 at trial entry
At least 1 measurable tumor lesion by RECIST 1.1
With histologically confirmed metastatic (Stage IV) small cell lung cancer (SCLC)
Patients must not have received any previous systemic treatment for small cell lung cancer
Patients must have an estimated life expectancy of more than 12 weeks
Patients must have an available recently-obtained, formalin-fixed, paraffin-embedded (FFPE) tissue sample containing tumor (biopsy preferably within 6 months) or a minimum number of 10 unstained slides, suitable for PD-L1 expression assessment.

Exclusion Criteria:

Patients with brain metastases are excluded, except those with brain metastases that have been treated with surgery or radiation and are clinically stable for at least 2 weeks prior to registration.
Prior therapy with any antibody or drug targeting T cell co-regulatory proteins, concurrent anticancer treatment, or immunosuppressive agents
Patients on current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)."
Known severe hypersensitivity reactions to monoclonal antibodies, history of anaphylaxis, or uncontrolled asthma, and persisting toxicity related to prior therapy of Grade > 1 NCI-CTCAE v 4.03.
Patients with active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent.
Patients with prior organ transplantation including allogenic stem-cell transplantation are excluded.
Patients with an active infection requiring systemic therapy are excluded.
Patients with known history of testing positive for HIV or known acquired immunodeficiency syndrome are excluded.
Also excluded are patients with Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive)
Vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines.
Persisting toxicity related to prior therapy
Other severe acute or chronic medical conditions.

Sites / Locations

Attikon University Hospital
Agii Anargiri Cancer Hospital
Metropolitan Hospital
Patra University Hospital
Henry Dunant Hospital Center
Alexandra Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Avelumab + Standard 1st line Chemotherapy

Arm Description

Administration of cisplatin or carboplatin + etoposide every 3 weeks with phased avelumab administered every 2 weeks until disease progression.

Outcomes

Primary Outcome Measures

1- year Progression Free Survival (PFS) Rate

Efficacy of treatment for 1- year PFS according to RECIST v1.1

Secondary Outcome Measures

Overall Survival Time (OS)

Best Overall Response (BOR).

Best Overall Response (BOR) according to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1). Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Stable disease (SD)=Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR.

Objective Response Rate (ORR).

Proportion of patients with CR or PR as the best overall response according to RECIST 1.1.

Duration of Response (DOR) according to RECIST Version 1.1

DOR will be determined according to RECIST 1.1, defined for each subject with a confirmed response as the time from the date of the first assessment demonstrating a CR or PR to date of the first assessment demonstrating PD or death from any cause within 12 weeks after the last tumor assessment, whichever occurs first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Stable disease (SD)=Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD is defined as at least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.

Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) According to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03

TEAEs will be defined as the adverse events (AEs) that occur between first dose of study drug administration and 90 days after the last dose of study drug administration that were absent before treatment or that worsened relative to pretreatment state.

Change from baseline in European Quality Of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire

The EQ-5D-5L Health Outcome Questionnaire is a measure of health status that provides a simple descriptive profile and a single index value. The EQ-5D-5L defines health in terms of mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The 5 items are combined to generate health profiles. These profiles were converted to a continuous single index score using a one to one matching. The lowest possible score is -0.59 (unable to walk, unable to self-care, unable to do usual activities, extreme pain or discomfort, extreme anxiety or depression) and the highest is 1.00 (no problems in all 5 dimensions).

Change from baseline in European Organization for the Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) Global Health Status

EORTC QLQ-C30 is a 30-question tool used to assess the overall quality of life (QoL) in cancer subjects. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, role, cognitive, emotional, social), and 9 symptom scales/items (Fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, financial impact. The EORTC QLQ-C30 GHS/QoL score ranges from 0 to 100; High score indicates better GHS/QoL. Score 0 represents: very poor physical condition and QoL. Score 100 represents: excellent overall physical condition and QoL.

Change from baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13)

EORTC QLQ-LC13 consists of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy. The 13 questions comprises 1 multi-item scale for dyspnea and 10 single-item symptoms and side effects (coughing, hemoptysis, sore mouth, dysphagia, neuropathy, alopecia, and medicine for pain). Score range: 0 (no burden of symptom domain or single symptom item) to 100 (highest burden of symptoms for symptom domains and single items).

Translational research

PD-L1 expression by immunohistochemistry on available tumour tissue collected from this study.

Full Information

NCT ID

NCT03568097

First Posted

May 30, 2018

Last Updated

June 1, 2023

Sponsor

Hellenic Cooperative Oncology Group

Collaborators

Merck KGaA, Darmstadt, Germany

1. Study Identification

Unique Protocol Identification Number

NCT03568097

Brief Title

Immunotherapy in Combination With Chemotherapy in Small-cell Lung Cancer

Acronym

PAVE

Official Title

Phased Avelumab Combined With Chemotherapy as First-line Treatment for Patients With Advanced Small-cell Lung Cancer (SCLC)

Study Type

Interventional

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

September 16, 2018 (Actual)

Primary Completion Date

March 30, 2022 (Actual)

Study Completion Date

April 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hellenic Cooperative Oncology Group

Collaborators

Merck KGaA, Darmstadt, Germany

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

PAVE(Phased Avelumab combined with chemotherapy as first-line treatment for patients with advanced small-cell lung cancer) is a Greek, investigator- initiated, single arm open- label phase II study of Avelumab in combination with cisplatin or carboplatin/ etoposide. The study will include an initial safety run-in, open-label, singlearm part (Part 1), and the actual phase II study (Part 2). The total number of patients will not change (the safety run-in patients will be included in the final total number of participants). The safety run-in period will not alter the total study timelines, as phase II accrual will follow immediately after the safety run-in.

Detailed Description

Advanced small cell lung cancer (SCLC) remains a disease with dismal prognosis and new therapeutics are urgently needed. SCLC is notably chemosensitive and first-line chemotherapy with platinum analogs and etoposide is associated with high rates of initial objective responses that unfortunately do not last long. The primary endpoint for study design is 1-year PFS rate, where according to RECIST v1.1 PFS is determined as the time from the date of study entry to the date of progression, death from any cause or date of last contact.Secondary End Point is the evaluation of efficacy of the study treatment in terms of Overall Survival (OS), Best Overall Response (BOR), Objective Response Rate (ORR) and Duration of Response (DOR). Evaluation of the safety of the study treatment by assessing Treatment-Emergent Adverse Events (TEAEs). Evaluation of the Quality of Life of patients receiving the study the study treatment. Evaluation of potential biomarkers on fresh or archival sample,of formalin-fixed paraffin embedded tumor tissue block or a minimum of 10 unstained tumor tissue sections. Moreover 10 ml of EDTA-stored blood sample will be collected as well.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Small Cell Lung Carcinoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

55 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Avelumab + Standard 1st line Chemotherapy

Arm Type

Experimental

Arm Description

Administration of cisplatin or carboplatin + etoposide every 3 weeks with phased avelumab administered every 2 weeks until disease progression.

Intervention Type

Drug

Intervention Name(s)

Avelumab

Other Intervention Name(s)

Bavencio

Intervention Description

10 mg/kg will be given as intravenous infusion (IV) every two weeks (q 2 weeks) until disease progression.

Primary Outcome Measure Information:

Title

1- year Progression Free Survival (PFS) Rate

Description

Efficacy of treatment for 1- year PFS according to RECIST v1.1

Time Frame

Time from inclusion in the trial up to 12 months

Secondary Outcome Measure Information:

Title

Overall Survival Time (OS)

Time Frame

Time from inclusion in the trial until the date of death due to any cause, up to 30 months.

Title

Best Overall Response (BOR).

Description

Time Frame

Time from inclusion in the trial up to 30 months.

Title

Objective Response Rate (ORR).

Description

Proportion of patients with CR or PR as the best overall response according to RECIST 1.1.

Time Frame

Time from inclusion in the trial up to 30 months.

Title

Duration of Response (DOR) according to RECIST Version 1.1

Description

Time Frame

Time from inclusion in the trial up to 30 months.

Title

Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) According to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03

Description

Time Frame

From the first dose of study drug treatment up to 90 days after the last dose of study drug administration

Title

Change from baseline in European Quality Of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire

Description

Time Frame

On Day 1 every 21 days for 18 weeks then monthly up to 30 months.

Title

Change from baseline in European Organization for the Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) Global Health Status

Description

Time Frame

On Day 1 every 21 days for 18 weeks then monthly up to 30 months.

Title

Change from baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13)

Description

Time Frame

On Day 1 every 21 days for 18 weeks then monthly up to 30 months.

Title

Translational research

Description

PD-L1 expression by immunohistochemistry on available tumour tissue collected from this study.

Time Frame

At baseline

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Signed written informed consent Male or female patients aged more than or equal to (≥) 18 years With Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1 at trial entry At least 1 measurable tumor lesion by RECIST 1.1 With histologically confirmed metastatic (Stage IV) small cell lung cancer (SCLC) Patients must not have received any previous systemic treatment for small cell lung cancer Patients must have an estimated life expectancy of more than 12 weeks Patients must have an available recently-obtained, formalin-fixed, paraffin-embedded (FFPE) tissue sample containing tumor (biopsy preferably within 6 months) or a minimum number of 10 unstained slides, suitable for PD-L1 expression assessment. Exclusion Criteria: Patients with brain metastases are excluded, except those with brain metastases that have been treated with surgery or radiation and are clinically stable for at least 2 weeks prior to registration. Prior therapy with any antibody or drug targeting T cell co-regulatory proteins, concurrent anticancer treatment, or immunosuppressive agents Patients on current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)." Known severe hypersensitivity reactions to monoclonal antibodies, history of anaphylaxis, or uncontrolled asthma, and persisting toxicity related to prior therapy of Grade > 1 NCI-CTCAE v 4.03. Patients with active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patients with prior organ transplantation including allogenic stem-cell transplantation are excluded. Patients with an active infection requiring systemic therapy are excluded. Patients with known history of testing positive for HIV or known acquired immunodeficiency syndrome are excluded. Also excluded are patients with Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive) Vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines. Persisting toxicity related to prior therapy Other severe acute or chronic medical conditions.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Helena Linardou, MD

Organizational Affiliation

1st Department on Medical Oncology, Metropolitan Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Attikon University Hospital

City

Chaïdári

State/Province

Athens

ZIP/Postal Code

12462

Country

Greece

Facility Name

Agii Anargiri Cancer Hospital

City

Néa Kifisiá

State/Province

Athens

ZIP/Postal Code

14564

Country

Greece

Facility Name

Metropolitan Hospital

City

Néo Fáliro

State/Province

Athens

ZIP/Postal Code

18547

Country

Greece

Facility Name

Patra University Hospital

City

Río

State/Province

Patra

ZIP/Postal Code

26504

Country

Greece

Facility Name

Henry Dunant Hospital Center

City

Athens

ZIP/Postal Code

115 26

Country

Greece

Facility Name

Alexandra Hospital

City

Athens

ZIP/Postal Code

11528

Country

Greece

12. IPD Sharing Statement

Learn more about this trial

Immunotherapy in Combination With Chemotherapy in Small-cell Lung Cancer

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