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Malignant Pleural MesotheliomaPhase 2NCT04480372

SAKK 17/18 (ORIGIN) MPM & NSCLC >1st Line Gemci & Atezo Ph II

A Phase 2 study testing Gemcitabine and Atezolizumab in people with Malignant Pleural Mesothelioma and Non-small Cell Lung Cancer, run by Swiss Cancer Institute at 12 sites in Switzerland.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

A significant number of patients with malignant pleural mesothelioma (MPM) and non-small cell lung cancer (NSCLC) are not cured with available treatments and will eventually relapse. After relapse treatment options are limited. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Gemcitabine and Atezolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
68 participants
Where
12 sitesSwitzerland
Study dates
17 Mar 2021to 3 Apr 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Written informed consent according to Swiss law and ICH/GCP regulations before registration and prior to any trial specific procedures including screening procedures.
  • For Cohort 1 (NSCLC): Patients with histologically- or cytologically- confirmed squamous or non-squamous metastatic NSCLC stage IIIB-IV (based on TNM classification). Patients must have experienced disease recurrence or progression during or after one or more prior immunotherapy or chemo-immunotherapy regimen for metastatic disease.
  • For Cohort 2 (MPM): Patients with histologically confirmed inoperable malignant pleural mesothelioma (MPM; with or without metastasis; all histological subtypes are eligible). Participants must have experienced disease recurrence or progression during or after one or more prior systemic therapy regimen for advanced or metastatic disease.
  • Patients with treated and stable CNS metastases are eligible, if:
  • Previous CNS-directed therapy has been completed at least 4 weeks prior to treatment start
  • No evidence of progression after completion of CNS-directed therapy as ascertained by clinical examination and brain imaging (MRI or CT).
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  • Patients with known HIV-infection are eligible, if:
  • CD4+ T-cell counts are ≥ 350 cells/ųl
  • No history of AIDS-defining opportunistic infection within past 12 months
  • Patient agrees to concomitant antiretroviral therapy (ART) if not currently on ART, or is on ART for ˃ 4 weeks and has a HIV viral load ˂ 400 copies/ml.
  • Patients with a previously treated malignancy are eligible if this is clinically stable and does not require concurrent tumor-directed treatment.
  • Exception: patients suffering from prostate cancer under hormonal ablation therapy (hormone sensitive disease) are eligible.
  • Patients with measurable disease according to RECIST 1.1 or mRECIST 1.1.
  • Availability of samples for translational research prior to treatment start. For the tumor samples either archival or freshly prepared biopsy samples (cytology is not allowed) are acceptable. Acceptable samples include core needle biopsies for deep tumor tissue (three cores; or in case only two cores can be obtained, there has to be tissue available in order to send 10 unstained slides considered by the local pathologist to be representative of the tumor) or excisional, incisional, punch, or forceps biopsies for cutaneous, subcutaneous, or mucosal lesions.
  • Age ≥ 18 years.
  • ECOG performance status 0-2.
  • Adequate bone marrow function: absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelet count ≥ 100 x 109/L, hemoglobin ≥ 90 g/L or ≥ 5.6 mmol/L.
  • Adequate hepatic function: total bilirubin ≤ 1.5 x ULN (except for patients with Gilbert's disease ≤ 3.0 x ULN), AST and ALT ≤ 2.5 x ULN, or ≤ 5 x ULN for patients with hepatic metastasis.
  • Adequate renal function: estimated glomerular filtration rate (eGFR) ≥ 40 ml/min/1.73 m2 (according to the Chronic Kidney Disease Epidemiology Collaboration) abbreviated formula CKD-EPI formula).
  • Women of childbearing potential, including women who had their last menstrual period in the last 2 years, must use highly effective contraception, are not pregnant or lactating and agree not to become pregnant during trial treatment and until 5 months after the last dose of investigational drug. A negative serum or urine pregnancy test before starting of trial treatment is required for all women of childbearing potential.
  • Men agree not to donate sperm or to father a child during trial treatment and until 5 months after the last dose of investigational drug (www.swissmedicinfo.ch).
  • Patients consent to the mandatory translational research projects providing the required samples.

Who cannot join

  • The presence of any one of the following exclusion criteria will lead to exclusion of the participant:
  • Symptomatic brain metastases indicative of active disease (defined as new and/or progressive brain metastases at the time of treatment start [38]) or leptomeningeal disease.
  • Prior treatment with gemcitabine in combination with atezolizumab.
  • NSCLC patients who progressed within the first 8 weeks from start of first line treatment.
  • NSCLC patients with activating EGFR or ALK mutations.
  • Known unstable or unresolved surgical or chemotherapy-related toxicity that would compromise trial treatment' duration.
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  • Concomitant or recent anti-cancer treatment (within 14 days prior to trial treatment start) with any other experimental drug (enrollment in another clinical trial).
  • Concomitant use of other anti-cancer drugs or radiotherapy (except for local pain control).
  • Cardiac disease NYHA 2 or greater.
  • Major surgery within 1 month prior to trial treatment start.
  • Known history of any uncontrolled active systemic infection requiring intravenous (i.v.) antimicrobial treatment.
  • Known history of tuberculosis, of primary immunodeficiency, of allogeneic tissue/solid organ transplant, of receipt of live attenuated vaccine within 28 days prior to treatment start.
  • History of interstitial lung disease (ILD) or severe pneumonitis (other than chronic obstructive pulmonary disease -COPD- exacerbation) that have required oral or i.v. steroids, or uncontrolled pleural effusion.
  • Concomitant use of systemic corticosteroids as premedication for chemotherapy.
  • Concomitant or prior use of systemic immunosuppressive medication (such as interferon, methotrexate) within 28 days prior to trial treatment start, with the exceptions local (i.e. intranasal, inhaled and topical) corticosteroids.
  • Any concomitant drugs contraindicated for use with the trial drugs according to the approved product information or to the Investigator' Brochure.
  • Known or suspected hypersensitivity to trial drug(s) or to any component of the trial drug(s).
  • Any other serious underlying medical, psychiatric, psychological, familial or geographical condition, which in the judgment of the investigator may interfere with the planned staging, treatment and follow-up, affect patient compliance or place the patient at high risk from treatment-related complications.

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

Switzerland12 sites

  • Kantonsspital Aarau

    Aarau, CH-5001

  • Kantonsspital Baden

    Baden, 5404

  • Universitaetsspital Basel

    Basel, 4031

  • St. Claraspital

    Basel

  • Inselspital

    Bern, 3010

  • Kantonsspital Graubuenden

    Chur, CH-7000

  • HFR Fribourg

    Fribourg, Villars-sur-Glâne, 1752

  • Hôpitaux Universitaires de Genève

    Geneva, 1211

  • Kantonsspital St. Gallen

    Sankt Gallen, CH-9007

  • Kantonsspital Winterthur

    Winterthur, CH-8400

  • UniversitätsSpital Zürich

    Zurich, 8091

  • Klinik Hirslanden Onkozentrum Zürich

    Zurich, CH-8032

Other trials in Switzerland

About this study

Official title: Overcoming Resistance to Immunotherapy Combining Gemcitabine With Atezolizumab in Advanced NSCLC and Mesothelioma Progressing Under Immune-checkpoint Inhibitors or Gemcitabine. A Multicenter, Single-arm, Open Label Phase II Trial With Two Cohorts

A significant number of patients with malignant pleural mesothelioma (MPM) and non-small cell lung cancer (NSCLC) are not cured with available treatments and will eventually relapse. After relapse treatment options are limited. Preclinical in vitro studies have demonstrated a synergism of immunotherapy with PD(L)1-targeting monoclonal antibodies and gemcitabine and ongoing clinical studies showed encouraging results.

The main objective of this trial is to determine the efficacy of chemotherapy (gemcitabine) combined with immunotherapy (atezolizumab) in patients with progressive NSCLC and MPM.

The trial treatments will be continued for max. 2 years or until discontinuation criteria are met. The follow-up phase will last up to 5 years from treatment start.

Read the detailed description

The trial combines two (Gemcitabine and Atezolizumab). Gemcitabine, alone or in combination regimens is a standard of care for several solid tumors, such as advanced or metastatic NSCLC. It is also used in an off-label setting for pre-treated MPM or naïve MPM in combination with platin-chemotherapy.

Atezolizumab is approved in the United States, European Union and in Switzerland for the treatment of NSCLC, urothelial carcinoma, small cell lung cancer (SCLC), triple-negative breast cancer (TNBC) and hepatocellular carcinoma (HCC) patients.

A significant number of patients with malignant pleural mesothelioma (MPM) and non-small cell lung cancer (NSCLC) are not cured with available treatments and will eventually relapse. After relapse treatment options are limited. Preclinical in vitro studies have demonstrated a synergism of immunotherapy with PD(L)1-targeting monoclonal antibodies and gemcitabine administered in different tumors models and ongoing clinical studies showed encouraging results. This may represent a safe and effective therapy for patients who relapsed or did not respond to standard therapies.

Patients will be treated with gemcitabine (1000 mg/m2 i.v. on day 1 and day 8 of each cycle, (every 3 weeks) and with atezolizumab (1200 mg i.v. on day 1 of each cycle, (every 3 weeks). The trial treatments will be continued for max. 2 years or until discontinuation criteria are met. The follow-up phase will last up to 5 years from treatment start.

The main objective of this trial is to determine the efficacy of chemotherapy (gemcitabine) combined with immunotherapy (atezolizumab) in patients with progressive NSCLC and MPM.

Keywords
non-small cell lung cancer, malignant pleural mesothelioma, Immunotherapy, Gemcitabine, Atezolizumab, phase II trial
Medical subject headings
Mesothelioma, Malignant, Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GemcitabineDrug

    Gemcitabine is administered at the dose of 1000 mg/m2 intravenously (i.v.) on day 1 and day 8 of each cycle (every 3 weeks).

  • AtezolizumabDrug

    Atezolizumab is administered at the dose of 1200 mg i.v. on day 1 of each cycle (every 3 weeks).

Study groups in NCT04480372
Study groupRoleWhat they receive
NSCLC (cohort 1) and inoperable MPM (cohort 2)ExperimentalCohort 1 consists of NSCLC patients. Cohort 2 consists of MPM patients. Patients will be treated with gemcitabine at the dose of 1000 mg/m2 i.v. on day 1 and day 8 of each cycle (every 3 weeks) and with atezolizumab at the dose of 1200 mg i.v. on day 1 of each cycle (every 3 weeks). The trial treatments will be continued for max. 2 years or until discontinuation criteria are met (see Ch. 9.3), whichever occurs first. The follow-up phase will last up to 5 years from treatment start.
Receives: Drug: Gemcitabine; Drug: Atezolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Primary endpoint for cohort 1: Objective response rate (ORR) according to RECIST 1.1

    ORR according to RECIST 1.1 is defined as the proportion of patients, whose best overall response is either complete response (CR) or partial response (PR) achieved during trial treatment until disease progression according to RECIST 1.1.

    Patients with CR or PR as best observed response during trial treatment will be considered as success; otherwise as failures for this endpoint.

    Patients without any tumor assessment or with non-evaluable response (NE) during trial treatment will be considered as failures for this endpoint.

    Measured: At the date of tumor assessment according to RECIST 1.1, assessed up to 2 years after registration

  2. Primary endpoint for cohort 2: ORR according to mRECIST

    ORR according to mRECIST is defined as the proportion of patients, whose best overall response is either complete response (CR) or partial response (PR) achieved during trial treatment until disease progression according to mRECIST.

    Patients with CR or PR as best observed response during trial treatment will be considered as success; otherwise as failures for this endpoint.

    Patients without any tumor assessment or with non-evaluable response (NE) during trial treatment will be considered as failures for this endpoint.

    Measured: At the date of tumor assessment according to mRECIST, assessed up to 2 years after registration

Secondary outcomes (12)

  1. For cohort 1 (NSCLC): Duration of response (DoR) according to RECIST 1.1

    DoR according to RECIST 1.1 is defined as the time from the first documentation of CR or PR (whichever occurs first) until disease progression according to RECIST 1.1 or death due to any cause.

    Patients not experiencing an event at the time of analysis and those starting a subsequent treatment without an event will be censored at the date of their last available tumor assessment before starting subsequent treatment, if any.

    This endpoint will be calculated for the subgroup of patients achieving CR or PR.

    Measured: From the time from the first documentation of CR or PR (whichever occurs first) until disease progression according to RECIST 1.1 or death due to any cause, assessed up to 5 years after registration

  2. For cohort 1 (NSCLC): Progression-free survival (PFS) according to RECIST 1.1

    PFS according to RECIST 1.1 is measured as the time from the first dose of atezolizumab/gemcitabine until disease progression according to RECIST 1.1 or death due to any cause.

    Patients not experiencing an event at the time of analysis and those receiving a subsequent treatment without an event will be censored at the date of their last available tumor assessment before starting subsequent treatment, if any.

    Measured: From the date of first dose of atezolizumab/gemcitabine until the date of progressive disease according to RECIST 1.1 or death due to any cause, whichever occurs first, assessed up to 5 years after the first registration

  3. For cohort 1 (NSCLC): Disease control rate (DCR) at 18 weeks according to RECIST 1.1

    DCR at 18 weeks according to RECIST 1.1 is defined as the proportion of patients, whose best overall response is either CR, PR or stable disease maintained for at least 18 weeks (SD≥18weeks) during trial treatment until disease progression according to RECIST 1.1.

    Patients with CR, PR, SD≥18weeks as best observed response during the trial treatment until disease progression according to RECIST 1.1 will be considered as success; otherwise as failures for this endpoint.

    Patients without any tumor assessment or with non-evaluable response (NE) during trial treatment will be considered as failures for this endpoint.

    Measured: At the date of tumor assessment according to RECIST 1.1, assessed up to 2 years after registration

  4. For cohort 2 (MPM): ORR according to mRECIST 1.1

    ORR according to mRECIST 1.1 is defined as the proportion of patients whose best overall response is either CR or PR achieved during trial treatment until disease progression according to mRECIST 1.1.

    Patients with CR or PR as best observed response will be considered as success; otherwise as failures for this endpoint.

    Patients without any tumor assessment or with non-evaluable response (NE) during trial treatment will be considered as failures for this endpoint.

    Measured: At the date of tumor assessment according to mRECIST 1.1, assessed up to 2 years after registration

  5. For cohort 2 (MPM): DoR according to mRECIST 1.1

    DoR according to mRECIST 1.1 is defined as the time from the first documentation of CR or PR (whichever occurs first) until disease progression according to mRECIST 1.1 or death due to any cause, whichever occurs first.

    Patients not experiencing an event at the time of analysis and those starting a subsequent treatment without an event will be censored at the date of their last available tumor assessment before starting subsequent treatment, if any.

    This endpoint will be calculated for the subgroup of patients achieving CR or PR.

    Measured: From the time from the first documentation of CR or PR (whichever occurs first) until disease progression according to mRECIST 1.1 or death due to any cause, assessed up to 5 years after registration

  6. For cohort 2 (MPM): PFS according to mRECIST 1.1

    PFS is defined as the time from the first dose of atezolizumab/gemcitabine until disease progression according to mRECIST 1.1 or death due to any cause.

    Patients not experiencing an event at the time of analysis and those receiving a subsequent treatment without an event will be censored at the date of their last available tumor assessment before starting subsequent treatment, if any.

    Measured: From the date of first dose of atezolizumab/gemcitabine until the date of progressive disease according to mRECIST 1.1 or death due to any cause, whichever occurs first, assessed up to 5 years after registration

  7. For cohort 2 (MPM): DCR at 18 weeks according to mRECIST 1.1

    DCR at 18 weeks according to mRECIST 1.1 is defined as the proportion of patients whose confirmed best overall response is either CR, PR or stable disease maintained for at least 18 weeks (SD≥18weeks) during trial treatment until disease progression according to mRECIST 1.1.

    Patients with CR, PR, SD18weeks as best observed response will be considered as success; otherwise as failures for this endpoint.

    Patients without any tumor assessment or with non-evaluable response (NE) during trial treatment will be considered as failures for this endpoint.

    Measured: At the date of tumor assessment according to mRECIST 1.1, assessed up to 2 years after registration

  8. For cohort 1 and cohort 2: Objective response rate according to iRECIST (iORR)

    iORR is defined as the proportion of patients whose best overall response is either (CR/iCR) or (PR/iPR) according to RECIST 1.1, modified RECIST 1.1 or iRECIST achieved during trial treatment until disease progression according to iRECIST.

    Patients with CR/iCR or PR/iPR as best observed response during trial treatment until disease progression according to iRECIST will be considered as a success; otherwise as failures for this endpoint.

    Patients without any tumor assessment or with non-evaluable response (NE) during trial treatment will be considered as failures for this endpoint.

    Measured: At the date of tumor assessment according to iRECIST, assessed up to 2 years after registration

  9. For cohort 1 and cohort 2: DoR according to iRECIST (iDoR)

    iDoR is defined as the time from the first documentation of CR/iCR or PR/iPR (whichever occurs first) according to RECIST 1.1, modified RECIST 1.1 or iRECIST achieved during trial treatment until disease progression according to iRECIST or death due to any cause.

    Patients not experiencing an event at the time of analysis and those starting a subsequent treatment without an event will be censored at the date of their last available tumor assessment before starting subsequent treatment, if any.

    This endpoint will be calculated for the subgroup of patients achieving CR/iCR or PR/iPR.

    Measured: From the time of documentation of CR or PR (whichever occurs first) until disease progression according to iRECIST or death due to any cause, assessed up to 5 years after registration

  10. For cohort 1 and cohort 2: PFS according to iRECIST (iPFS)

    iPFS is defined as the time from the first dose of atezolizumab/gemcitabine until disease progression according to iRECIST or death due to any cause.

    Patients not experiencing an event at the time of analysis and those receiving a subsequent treatment without an event will be censored at the date of their last available tumor assessment before starting subsequent treatment, if any.

    Measured: From the date of first dose of treatment until the date of progressive disease according to iRECIST or death due to any cause, whichever occurs first, assessed up to 5 years after registration

  11. For cohort 1 and cohort 2: Overall Survival (OS)

    OS is defined as the time from the first dose of atezolizumab/gemcitabine until death due to any cause. Patients alive or lost to follow-up will be censored at the last date where they were known to be alive.

    Measured: From the date of from the first dose of atezolizumab/gemcitabine until the date of death from any cause, assessed up to 5 years after registration

  12. For cohort 1 and cohort 2: Adverse events (AEs) will be assessed according to CTCAE v5.0.

    AEs will be assessed according to CTCAE v5.0.

    Measured: Up to 5 years after registration

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Jul 2020
  2. Study start17 Mar 2021
  3. Primary completion10 Mar 2023
  4. Study completion3 Apr 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
A multicenter, single-arm, open label phase II trial with two cohorts.
Masking
None (open label)
Enrolment
68 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04480372
Sponsor's protocol ID
SAKK 17/18
Status last verified
Jun 2024
First submitted
17 Jul 2020
Last updated
1 Jul 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Gemcitabine and Atezolizumab in people with Malignant Pleural Mesothelioma and Non-small Cell Lung Cancer, run by Swiss Cancer Institute at 12 sites in Switzerland.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Primary endpoint for cohort 1: Objective response rate (ORR) according to RECIST 1.1 (time frame: At the date of tumor assessment according to RECIST 1.1, assessed up to 2 years after registration). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04480372.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2024.

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