Clinical Trials /

Fostering Efficacy of Anti - PD-1 - Treatment: Nivolumab Plus Radiotherapy in Advanced NSCLC

NCT03044626

Description:

AIO-YMO/TRK-0415 (FORCE) is a Phase 2, open-label of nivolumab, patients with metastatic non-squamous NSCLC with the necessity of radiotherapy of a metastatic site (e.g. bone) in 2nd-line or 3rd-line treatment for study group A and patients with metastatic non-squamous NSCLC without the necessity of radiotherapy in 2nd-line or 3rd-line treatment for study Group B.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Fostering Efficacy of Anti - PD-1 - Treatment: Nivolumab Plus Radiotherapy in Advanced NSCLC
  • Official Title: Fostering Efficacy of Anti - PD-1 - Treatment: Nivolumab Plus Radiotherapy in Advanced NSCLC

Clinical Trial IDs

  • ORG STUDY ID: AIO-YMO/TRK-0415
  • SECONDARY ID: 2015-005741-31
  • SECONDARY ID: CA209-430
  • NCT ID: NCT03044626

Conditions

  • Carcinoma,Non-Small-Cell Lung
  • Metastatic Lung Cancer
  • Nonsmall Cell Lung Cancer
  • Lung Adenocarcinoma Metastatic
  • Large Cell Lung Carcinoma Metastatic

Interventions

DrugSynonymsArms
Radiotherapystudy group A
Nivolumabstudy group A

Purpose

AIO-YMO/TRK-0415 (FORCE) is a Phase 2, open-label of nivolumab, patients with metastatic non-squamous NSCLC with the necessity of radiotherapy of a metastatic site (e.g. bone) in 2nd-line or 3rd-line treatment for study group A and patients with metastatic non-squamous NSCLC without the necessity of radiotherapy in 2nd-line or 3rd-line treatment for study Group B.

Detailed Description

      The primary objective is to investigate efficacy of a nivolumab-radiotherapy combination
      treatment in metastatic non-squamous NSCLC patients.
    

Trial Arms

NameTypeDescriptionInterventions
study group AExperimentalPatients with metastatic non-squamous NSCLC with the necessity of radiotherapy of a metastatic site (e.g. bone) in 2nd-line or 3rd-line treatment: Nivolumab 240 mg fixed dose (q2w). First dose followed by radiotherapy. Radiotherapy has to start at the latest 72 hours after nivolumab administration. Radiotherapy: A metastatic site will be treated with a radiation dose of 4 Gy for a total of 5 courses during a two week time interval (total dose 20 Gy)
  • Radiotherapy
  • Nivolumab
study group BOtherPatients with metastatic non-squamous NSCLC without the necessity of radiotherapy in 2nd-line or 3rd-line treatment: Nivolumab 240 mg fixed dose (q2w).
  • Nivolumab

Eligibility Criteria

        Inclusion criteria

        1. Written informed consent and any locally-required authorization (EU Data Privacy
        Directive in the EU) obtained from the subject prior to performing any protocol-related
        procedures, including screening evaluations.

        2. Subject is willing and able to comply with the protocol for the duration of the study
        including undergoing treatment and scheduled visits and examinations including follow up.

        3. Age ≥ 18 years at time of study entry. 4. ECOG performance status 0-1. 5. Patients with
        measurable disease (at least one uni-dimensionally measurable target lesion by CT-scan or
        MRI) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) are eligible.
        For patients in group A, non-measurable and measurable lesions may be chosen for
        irradiation. However, in order to allow for evaluation of abscopal effects, patients in
        group A must have at least one measurable lesion beside the lesion planned to be
        irradiated. Lesions planned to be irradiated may not be defined as a measurable target
        lesion. Radiographic tumor assessment must be performed within 28 days before initiation of
        study treatment.

        6. Target Lesions may be located in a previously irradiated field if there is documented
        (radiographic) disease progression in that site.

        7. Patients with metastatic non-squamous non-small cell lung cancer in 2nd-line and
        3rd-line treatment and

          1. no necessity of radiotherapy or

          2. the necessity of radiotherapy of a metastatic bone lesion or soft tissue lesion.

               -  Patients with intrathoracic metastases or intrathoracic progressive disease will
                  be included if radiotherapy of the lung parenchyma is NOT required

               -  Subjects with symptomatic brain metastases are eligible if metastases have been
                  treated and treatment has been completed at least 12 weeks before inclusion in
                  this study for group B and 2 weeks for group A. Moreover, there must be no
                  magnetic resonance imaging (MRI) evidence of progression within 28 days prior to
                  the first dose of nivolumab administration. There must also be no requirement for
                  immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone
                  equivalents) for at least 2 weeks prior to study drug administration. Patients
                  with stable/asymptomatic brain metastases that do not require local therapy with
                  irradiation (whole brain irradiation or stereotactic brain irradiation) can be
                  included. In ambiguous cases, consultation with the LKP or his/her delegate is
                  advised.

                  8. Patients who will receive study therapy after acceptable prior therapy as
                  specified below are eligible: i. Patients who will receive study therapy as
                  2nd-line or 3rd-line of treatment:

                    1. Patients must have experienced disease recurrence or progression during or
                       after one prior platinum doublet-based chemotherapy regimen for advanced or
                       metastatic disease.

                       First line therapy is defined as therapy used to treat advanced disease.
                       Each subsequent line of therapy is preceded by disease progression. A switch
                       of an agent within a regimen in order to manage toxicity does not define the
                       start of a new line of therapy. Subjects must have received at least 2
                       cycles of platinum doublet based chemotherapy before discontinuation for
                       toxicity.

                       Experimental therapies when given as separate regimen are considered as
                       separate line of therapy.

                       Maintenance therapy following platinum doublet-based chemotherapy is not
                       considered as a separate regimen of therapy and could comprise continuation
                       of one or more of the agents used in the first-line therapy regimen or
                       switch to another non cross-resistant agent. The initiation of maintenance
                       therapy requires the lack of progressive disease with front-line therapy.

                       Treatment given for locally advanced disease is not considered as a line of
                       therapy for advanced disease. Subjects with recurrent disease > 6 months
                       after platinum-containing adjuvant, neoadjuvant or definitive chemoradiation
                       therapy given for locally advanced disease, who also subsequently progressed
                       during or after a platinum doublet-based regimen given to treat the
                       recurrence, are eligible.

                    2. Patients who received platinum-containing adjuvant, neoadjuvant or
                       definitive chemoradiation therapy given for locally advanced disease, and
                       developed recurrent (local or metastatic) disease within 6 months of
                       completing therapy are eligible.

                       Adjuvant or neoadjuvant platinum-doublet chemotherapy (after surgery and/or
                       radiation therapy) followed by recurrent or metastatic disease within 6
                       months of completing therapy is considered as first line therapy for
                       advanced disease.

                  9. A formalin fixed, paraffin-embedded (FFPE) tumor tissue block (archival or
                  recent) or a minimum of 15 unstained slides of tumor sample (2-3 µm sections,
                  slices must be recent and collected on slides provided by the sponsor) must be
                  available for biomarker (PD-L1) evaluation. Biopsy should be excisional,
                  incisional or core needle. Fine needle aspiration is insufficient.

                  10. Prior therapies and surgeries are allowed if completed 2 weeks for minor
                  surgery (group A and B) or 12 weeks for any previous radiotherapy for group B,
                  respectively prior to start of treatment and patient recovered from toxic
                  effects. For group A, any prior radiotherapy not involving the lungs must be
                  completed 2 weeks prior to start of treatment. A prior radiotherapy involving the
                  lungs must be completed 12 weeks prior to start of treatment.

                  11. Subjects must have recovered from the effects of major surgery or significant
                  traumatic injury at least 14 days before the first dose of study treatment.

                  12. Adequate blood count, liver-enzymes, and renal function (obtained no later
                  than 14 days prior to start of treatment): WBC ≥ 2000/μL Neutrophils ≥ 1500/μL
                  Platelets ≥ 100 x103/μL Hemoglobin ≥ 9.0 g/dL

             Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min (if using the
             Cockcroft-Gault formula below):

             Female CrCl = ((140 - age in years) x weight in kg x 0.85) / (72 x serum creatinine in
             mg/dL)

             Male CrCl = ((140 - age in years) x weight in kg x 1.00) / (72 x serum creatinine in
             mg/dL)

             AST/ALT ≤ 3 x ULN Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome,
             who can have total bilirubin < 3.0 mg/dL)

             13. Women of childbearing potential (WOCBP) must use appropriate method(s) of
             contraception. WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30
             days plus the time required for nivolumab to undergo five half-lives) after the last
             dose of nivolumab.

             14. Women of childbearing potential must have a negative serum pregnancy test (minimum
             sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of
             nivolumab.

             15. Men who are sexually active with WOCBP must use any contraceptive method with a
             failure rate of less than 1% per year. Men receiving nivolumab and who are sexually
             active with WOCBP will be instructed to adhere to contraception for a period of 31
             weeks after the last dose of investigational product. Women who are not of
             childbearing potential (ie, who are postmenopausal or surgically sterile as well as
             azoospermic men do not require contraception).

             Exclusion criteria

               1. Previous malignancy (other than NSCLC), which either progresses or requires
                  active treatment.

                  Subjects with previous malignancies (except non-melanoma skin cancers, and the
                  following in situ cancers: bladder, gastric, colon, cervical/dysplasia,
                  endometrial, melanoma, or breast) are excluded unless a complete remission was
                  achieved at least 2 years prior to study entry AND no additional therapy is
                  required or anticipated to be required during the study period.

               2. Brain metastases mandating active treatment in terms of irradiation (whole brain
                  irradiation or stereotactic brain irradiation). As stated in 3.2 point 7 b,
                  subjects with brain metastases are eligible if metastases have been treated and
                  treatment has been completed at least 12 weeks before inclusion in this study for
                  group B and 2 weeks for group A. Moreover, there must be no magnetic resonance
                  imaging (MRI) evidence of progression within 28 days prior to the first dose of
                  nivolumab administration. There must also be no requirement for immunosuppressive
                  doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at
                  least 2 weeks prior to study drug administration. Patients with
                  stable/asymptomatic brain metastases that do not require local therapy with
                  irradiation (whole brain irradiation or stereotactic brain irradiation) can be
                  included. In ambiguous cases, consultation with the LKP or his/her delegate is
                  advised.

               3. Known activating EGFR mutation or a known ALK translocation.

               4. Prior therapy with anti-tumor vaccines or other immuno-stimulatory antitumor
                  agents.

               5. Patients with interstitial lung disease.

               6. Any previous treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4
                  antibody, or any other antibody or drug specifically targeting T‑cell
                  co-stimulation or immune checkpoint pathways

               7. All toxicities attributed to prior anti-cancer therapy other than alopecia and
                  fatigue must have resolved to grade 1 (NCI CTCAE version 4) or baseline before
                  administration of study drug.

               8. Patients should be excluded if they have an active, known or suspected autoimmune
                  disease. NOTE: Subjects are permitted to enroll if they have vitiligo, type I
                  diabetes mellitus, residual hypothyroidism due to autoimmune condition only
                  requiring hormone replacement, psoriasis not requiring systemic treatment, or
                  conditions not expected to recur in the absence of an external trigger

               9. Patients should be excluded if they have a condition requiring systemic treatment
                  with either corticosteroids (> 10 mg daily prednisone equivalents) or other
                  immunosuppressive medications within 14 days of study drug administration. NOTE:
                  Inhaled or topical steroids and adrenal replacement doses > 10 mg daily
                  prednisone equivalents are permitted in the absence of active autoimmune disease.

              10. Patients should be excluded if they are positively tested for hepatitis B virus
                  surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody)
                  indicating acute or chronic infection

              11. Patients should be excluded if they have known history of testing positive for
                  human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome
                  (AIDS).

              12. History of severe hypersensitivity reactions to other monoclonal antibodies or
                  any excipient.

              13. Female subjects who are pregnant, breast-feeding or male or female patients of
                  reproductive potential who are not employing an effective method of birth control
                  (failure rate of less than 1% per year)

              14. Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy,
                  endocrine therapy, targeted therapy, biologic therapy, tumor embolization,
                  monoclonal antibodies, other investigational agent) ≤14 days prior to the first
                  dose of study treatment.

              15. Any other serious or uncontrolled medical disorder, active infection, physical
                  examining, laboratory finding, altered mental status, or psychiatric condition
                  that, in the opinion of the investigator, would limit a subject's ability to
                  comply with the study requirements, substantially increase risk to the subject,
                  or impact the interpretability of study results.

              16. History of solid organ or tissue transplantation including allogenic
                  hematopoietic stem cell transplantation.

              17. Previous enrollment in the present study.

              18. Involvement in the planning and/or conduct of the study (applies to both BMS
                  staff and/or staff of sponsor and study site)

              19. Patient who might be dependent on the sponsor, site or the investigator.

              20. Patient who has been incarcerated or involuntarily institutionalized by court
                  order or by the authorities § 40 Abs. 1 S. 3 Nr. 4 AMG.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:objective response rate (ORR) according to RECIST 1.1 criteria
Time Frame:through study completion, an average of 18 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:progression free survival (PFS)
Time Frame:approx. 6 months
Safety Issue:
Description:
Measure:PFS using assessment according to irRECIST
Time Frame:approx. 6 months
Safety Issue:
Description:Immune-related Response Evaluation Criteria In Solid Tumors (irRECIST)
Measure:ORR using assessment according to irRECIST
Time Frame:approx. 6 months
Safety Issue:
Description:Immune-related Response Evaluation Criteria In Solid Tumors (irRECIST)
Measure:Overall Survival (OS)
Time Frame:approx. 57 months
Safety Issue:
Description:
Measure:Adverse Events
Time Frame:approx. 36 months
Safety Issue:
Description:Adverse Events: Type, incidence, and severity according to NCI CTCAE version 4.03
Measure:Assesment of Quality of life
Time Frame:approx. 57 months
Safety Issue:
Description:as determined with FACT-L (Functional Assessment of Cancer Therapy - Lung)

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:AIO-Studien-gGmbH

Trial Keywords

  • Nivolumab
  • Radiotherapy

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