Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 2 of 3 for:    IMpower133 | Lung Cancer

Thoracic RadiothErapy With Atezolizumab in Small Cell lUng canceR Extensive Disease (TREASURE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04462276
Recruitment Status : Recruiting
First Posted : July 8, 2020
Last Update Posted : August 20, 2020
Sponsor:
Collaborator:
Thoraxklinik-Heidelberg gGmbH
Information provided by (Responsible Party):
Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

Brief Summary:
This is a multicenter phase 2 clinical trial to investigate the treatment efficacy and feasibility of combining thoracic radiotherapy (TRT) with the IMpower133 regimen in the upfront treatment of ED SCLC patients. Patients with a response after induction therapy with carboplatin/etoposide and atezolizumab will be included into this study to subsequently receive atezolizumab maintenance therapy and will be randomized to receive TRT or not. This trial aims to i.) increase the efficacy of combined atezolizumab- and chemotherapy by adding radiotherapy and ii.) determine the safety and tolerability of the combination of chemotherapeutic, immunological and radiological treatment in the first-line setting of advanced SCLC, and iii.) to collect tumor tissue as well as blood and stool samples for separate biomarker research project.

Condition or disease Intervention/treatment Phase
Small Cell Lung Cancer Extensive Stage Thoracic Radiotherapy Drug: Atezolizumab Radiation: thoracic radiotherapy (TRT) Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 104 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized, open label, multicenter, phase II trial
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Thoracic RadiothErapy With Atezolizumab in Small Cell lUng canceR Extensive Disease: a Randomized, Open-label, Multicenter Phase II Study
Actual Study Start Date : July 28, 2020
Estimated Primary Completion Date : July 2024
Estimated Study Completion Date : July 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm A: Atezolizumab + thoracic radiotherapy
Atezolizumab at a fixed dose of 1,200 mg as an IV infusion, on day 1, to be repeated every 3 weeks (Q3W) Thoracic radiation therapy (TRT), 30 Gy in 10 fractions
Drug: Atezolizumab
fixed dose of 1,200 mg as an IV infusion, on day 1, to be repeated every 3 weeks (Q3W)

Radiation: thoracic radiotherapy (TRT)
30 Gy in 10 fractions

Experimental: Arm B: Atezolizumab
Atezolizumab at a fixed dose of 1,200 mg as an IV infusion, on day 1, to be repeated every 3 weeks (Q3W)
Drug: Atezolizumab
fixed dose of 1,200 mg as an IV infusion, on day 1, to be repeated every 3 weeks (Q3W)




Primary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: at 24 month after lat patient randomized ]
    time from randomization to death


Secondary Outcome Measures :
  1. 1-year Overall Survival (OS) rate [ Time Frame: at 1 year after randomization ]
    OS rate after 1 year after randomization

  2. 2-year Overall Survival (OS) rate [ Time Frame: at 2 years after randomization ]
    OS rate after 2 years after randomization

  3. Progression-free survival (PFS) [ Time Frame: at study end (approx. 2 years after last patient randomized) ]
    PFS is defined as time from randomization to the date of first observed disease progression (investigator assessment according to RECIST 1.1) or death from any cause

  4. objective response rate (ORR) [ Time Frame: at study end (approx. 2 years after last patient randomized) ]
    ORR will be assessed according to RECIST 1.1. The objective response rate will be defined as the proportion of allocated / randomized subjects with best response of complete or partial response.

  5. Intrathoracic tumor control [ Time Frame: at study end (approx. 2 years after last patient randomized) ]
    rate of intrathoracic progression will be determined via assessing the proportion of allocated / randomized subjects with an intrathoracic progression (investigator assessment according to RECIST 1.1).

  6. Incidence, nature, causal relationship and severity of Adverse Events [ Time Frame: at study end (approx. 2 years after last patient randomized) ]
    Incidence, nature, causal relationship and severity of Adverse Events according to CTC v5.0

  7. Frequency of abnormal laboratory parameters [ Time Frame: at study end (approx. 2 years after last patient randomized) ]
    Frequency of abnormal laboratory parameters

  8. frequency of treatment withdrawal [ Time Frame: at study end (approx. 2 years after last patient randomized) ]
    description of relative and absolute frequencies of treatment withdrawal (either due to adverse events or other reasons), which will be compared between treatment groups

  9. completion of radiotherapy [ Time Frame: at study end (approx. 2 years after last patient randomized) ]
    relative and absolute numbers of radiotherapy completers

  10. Cancer related quality of life (Functional Assessment of Cancer Therapy for patients with Lung cancer (FACT-L)) [ Time Frame: at study end (approx. 2 years after last patient randomized) ]
    Cancer-related quality of life measured via the total- and subscores of FACT-L will be compared between the two treatments by analyzing the mean change from baseline. Score scales are ranging from 0 (minimum) to 4 (maximum).


Other Outcome Measures:
  1. Collection of biomarker samples for separate biomarker research project [ Time Frame: at study end (approx. 2 years after last patient randomized) ]
    Collection of biomarker samples for separate biomarker research project



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Fully-informed written consent and locally required authorization (European Union [EU] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
  2. Age ≥ 18 years.
  3. Histologically or cytologically confirmed ED SCLC as defined according to the Veterans Administration Lung Study Group staging system.
  4. Measurable ED SCLC according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1
  5. ECOG performance-status score of 0 or 1 at screening
  6. Any response after four cycles of standard chemo-immunotherapy (carboplatin, etoposide, atezolizumab) defined as CR/PR or thoracic SD with CR/PR of extrathoracic lesions as per RECIST 1.1
  7. Thoracic treatment volume considered treatable using acceptable radiation fields as judged by a radiation oncologist
  8. 28 ± 7 days or less between last administration of chemo-immunotherapy (carboplatin, etoposide, atezolizumab) and randomization.
  9. Patients with a history of treated CNS metastases are eligible, if there is no ongoing requirement for corticosteroids as therapy for CNS disease. Before randomization, MRI of brain (with contrast, unless contraindicated) is recommended in subjects with suspected or known brain metastases, as per local standard., Patients with asymptomatic brain metastases that do not require local therapy with irradiation (whole brain irradiation) can be included. In ambiguous cases, consultation with the LKP or his/her delegate is advised.
  10. No previous radiotherapy to thorax
  11. Availability of pre-treatment tumor tissue specimen
  12. The patient is willing and able to comply with the protocol for the duration of the study, including hospital visits for treatment and scheduled follow-up visits and examinations.
  13. FEV1 ≥ 40% (Best)
  14. Adequate bone marrow and renal function including the following:

    • Hemoglobin ≥ 9.0 g/dL;
    • absolute neutrophil count ≥ 1.0 x 103/L;
    • platelets ≥75x 109/L;
    • Calculated creatinine clearance ≥30 mL/min as determined by the Cockcroft-Gault equation
  15. Adequate hepatic function (with stenting for any obstruction, if required) including the following:

    • Serum bilirubin ≤ 3 x institutional upper limit of normal (ULN);
    • AST (SGOT) / ALT (SGPT) and alkaline phosphatase ≤ 2.5x ULN

    Following exceptions apply:

    • Patients with documented liver metastases: AST and/or ALT ≤ 5x ULN
    • Patients with documented liver or bone metastases: alkaline phosphatase ≤ 5x ULN.
  16. Female patients with reproductive potential must have a negative urine or serum pregnancy test within 7 days prior to start of trial.
  17. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:

    • Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
    • Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).

Exclusion Criteria:

  1. History of autoimmune disease and previous treatment with CD137 agonists, immune-checkpoint blockade therapies, anti-PD-1, or anti-PD-L1 therapeutic antibodies.
  2. Prior therapy for limited-stage SCLC with curative intent.
  3. Prior thoracic radiotherapy within the past 5 years before the first dose of study drug.
  4. Oxygen-dependent medical condition.
  5. History or current radiology suggestive of interstitial lung disease.
  6. History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
  7. Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study, or during the follow-up period of an interventional study.
  8. Participation in another clinical study with an investigational product within 21 days prior to the first dose of the study treatment.
  9. Any concurrent chemotherapy, investigational product (IMP), biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer related conditions (eg, hormone replacement therapy) is acceptable.
  10. Major surgery (as defined by the Investigator) within 4 weeks prior to enrollment into the study; patients must have recovered from effects of any major surgery. Note: Local non-major surgery for palliative intent is acceptable.
  11. Active or prior documented autoimmune or inflammatory disorders (including but not limited to diverticulitis [with the exception of diverticulosis], celiac disease, systemic lupus erythematosus, Sarcoidosis, or Wegener's syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis). The following are exceptions to this criterion:

    • Patients with vitiligo or alopecia
    • Patients with hypothyroidism (e.g., following Hashimoto's disease) stable on hormone replacement
    • Patients with controlled Type I diabetes mellitus on an insulin regimen
    • Any chronic skin condition that does not require systemic therapy
    • Patients without active disease in the last 5 years may be included but only after consultation with the study physician.
  12. Active, uncontrolled inflammatory bowel disease [e.g. ulcerative colitis or Crohn's disease]. Patients in stable remission for more than 1 year may be included.
  13. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, interstitial lung disease, gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
  14. History of another primary malignancy except for:

    • Malignancy treated with curative intent and with no known active disease ≥ 5 years before the first dose of IMP and of low potential risk for recurrence
    • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
    • Adequately treated carcinoma in situ without evidence of disease
  15. History of active primary immunodeficiency
  16. History of allogenic organ or tissue transplantation.
  17. Clinical diagnosis of active tuberculosis.
  18. Positive testing for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  19. Positive testing for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
  20. Current or prior use of immunosuppressive medication within 14 days before the first dose of atezolizumab. The following are exceptions to this criterion:

    • Intranasal, inhaled, topical steroids, or local steroid injections (e.g. intra articular injection)
    • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
    • Steroids as premedication for hypersensitivity reactions (e.g. CT scan premedication)
  21. Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 5 months after the last dose of atezolizumab monotherapy.
  22. Known allergy or hypersensitivity to the IMP or any of the constituents of the product.
  23. Any co-existing medical condition that in the investigator's judgement will substantially increase the risk associated with the patient's participation in the study.
  24. Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities.
  25. Patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial and therefore cannot form a rational intention in the light of the facts

Information from the National Library of Medicine

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): NCT04462276


Contacts
Layout table for location contacts
Contact: Farastuk Bozorgmehr, Dr. med. +49 6221 396 8077 farastuk.bozorgmehr@med.uni-heidelberg.de
Contact: Johanna Riedel, Dr. +496976014635 riedel.johanna@ikf-khnw.de

Locations
Layout table for location information
Germany
Thoraxklinik am Universitätsklinikum Heidelberg Recruiting
Heidelberg, Germany, 69126
Contact: Farastuk Bozorgmehr, Dr.    +49 6221 396 ext 8807    farastuk.bozorgmehr@med.uni-heidelberg.de   
Sponsors and Collaborators
Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
Thoraxklinik-Heidelberg gGmbH
Investigators
Layout table for investigator information
Principal Investigator: Farastuk Bozorgmehr, Dr. med. Thoraxklinik at Heidelberg University
Layout table for additonal information
Responsible Party: Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
ClinicalTrials.gov Identifier: NCT04462276    
Other Study ID Numbers: TREASURE
First Posted: July 8, 2020    Key Record Dates
Last Update Posted: August 20, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: No IPD will be shared.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest:
SCLC
thoracic radiotherapy
Atezolizumab
Additional relevant MeSH terms:
Layout table for MeSH terms
Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Bronchial Neoplasms
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Atezolizumab
Antineoplastic Agents