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

NCT04480372 | Completed Phase 2 DMC

• 1 other identifier: SAKK 17/18
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 12

Brief 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. 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.

Conditions

Malignant Pleural Mesothelioma; Non-small Cell Lung Cancer

Keywords

non-small cell lung cancer; malignant pleural mesothelioma; Immunotherapy; Gemcitabine; Atezolizumab; phase II trial

Outcome Measures

Primary Outcomes (2)

• 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.

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

• 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.

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

Secondary Outcomes (12)

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

  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

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

  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

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

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

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

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

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

  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

Study Arms (1)

NSCLC (cohort 1) and inoperable MPM (cohort 2)

EXPERIMENTAL

Cohort 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.

Drug: Gemcitabine; Drug: Atezolizumab

Interventions

Gemcitabine DRUG

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).

NSCLC (cohort 1) and inoperable MPM (cohort 2)

Atezolizumab DRUG

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

NSCLC (cohort 1) and inoperable MPM (cohort 2)

Eligibility Criteria

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

You may qualify if:

• 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).
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (12)

HFR Fribourg

Fribourg, Villars-sur-Glâne, 1752, Switzerland

Location

Kantonsspital Aarau

Aarau, CH-5001, Switzerland

Location

Kantonsspital Baden

Baden, 5404, Switzerland

Location

Universitaetsspital Basel

Basel, 4031, Switzerland

Location

St. Claraspital

Basel, Switzerland

Location

Inselspital

Bern, 3010, Switzerland

Location

Kantonsspital Graubuenden

Chur, CH-7000, Switzerland

Location

Hôpitaux Universitaires de Genève

Geneva, 1211, Switzerland

Location

Kantonsspital St. Gallen

Sankt Gallen, CH-9007, Switzerland

Location

Kantonsspital Winterthur

Winterthur, CH-8400, Switzerland

Location

UniversitätsSpital Zürich

Zurich, 8091, Switzerland

Location

Klinik Hirslanden Onkozentrum Zürich

Zurich, CH-8032, Switzerland

Location

MeSH Terms

Conditions

Mesothelioma, Malignant; Carcinoma, Non-Small-Cell Lung

Interventions

Gemcitabine; atezolizumab

Condition Hierarchy (Ancestors)

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Alessandra Curioni Fontecedro, MD

  University of Zurich

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A multicenter, single-arm, open label phase II trial with two cohorts.

Study Record Dates

• First Submitted: July 17, 2020
• First Posted: July 21, 2020
• Study Start: March 17, 2021
• Primary Completion: March 10, 2023
• Study Completion: April 3, 2024
• Last Updated: July 1, 2024

Record last verified: 2024-06

Locations

CH (12)