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:

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. Expected life expectancy of ≥ 6 months.

          6. 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.

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

          8. 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 there is no magnetic resonance imaging (MRI) evidence of
                       progression for 12 weeks after treatment is complete and 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. Moreover, patients with stable (asymptomatic) brain
                       metastases that do not require local therapy with WBI (whole brain
                       irradiation) can be included.

          9. Patients who will receive study therapy after acceptable prior therapy as specified
             below are eligible:

             a) Patients who will receive study therapy as 2nd-line or 3rd-line of treatment:

             • 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.

             • 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.

         10. A formalin fixed, paraffin-embedded (FFPE) tumor tissue block (archival or recent) or
             a minimum of 15 unstained slides of tumor sample (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.

         11. Prior therapies and surgeries are allowed if completed 2 weeks (for minor surgery) or
             12 weeks (for palliative radiotherapy for bone pain), respectively prior to start of
             treatment and patient recovered from toxic effects.

         12. 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.

         13. 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 x10^3/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)

               -  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)

         14. 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.

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

         16. 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 WBI (whole brain irradiation).
             Subjects with brain metastases are eligible if metastases have been treated and there
             is no magnetic resonance imaging (MRI) evidence of progression for 12 weeks after
             treatment is complete and 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.

          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 symptomatic interstitial lung disease.

          6. Any previous treatment with a 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 exam
             finding, 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. Previous enrollment in the present study.

         17. Involvement in the planning and/or conduct of the study (applies to both BMS
             [Bristol-Myers Squibb GmbH & Co. KGaA] staff and/or staff of sponsor and study site)

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

         19. 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: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

Last Updated

January 8, 2018