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Carcinoma，Non-Small-Cell LungPhase 2FORCENCT03044626

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

A Phase 2 study testing Radiotherapy and Nivolumab in people with Carcinoma，Non-Small-Cell Lung and Metastatic Lung Cancer, run by AIO-Studien-gGmbH at 16 sites in Germany.

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

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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Radiotherapy and Nivolumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
101 participants
Where
16 sitesGermany
Study dates
10 Feb 2017to 31 Dec 2020
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

  • 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
  • no necessity of radiotherapy or
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  • 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:
  • 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.
  • 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).

Who cannot join

  • 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.
  • 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.
  • Known activating EGFR mutation or a known ALK translocation.
  • Prior therapy with anti-tumor vaccines or other immuno-stimulatory antitumor agents.
  • Patients with interstitial lung disease.
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  • 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
  • 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.
  • 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
  • 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.
  • 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
  • Patients should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
  • History of severe hypersensitivity reactions to other monoclonal antibodies or any excipient.
  • 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)
  • 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.
  • 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.
  • History of solid organ or tissue transplantation including allogenic hematopoietic stem cell transplantation.
  • Previous enrollment in the present study.
  • Involvement in the planning and/or conduct of the study (applies to both BMS staff and/or staff of sponsor and study site)
  • Patient who might be dependent on the sponsor, site or the investigator.
  • Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities § 40 Abs. 1 S. 3 Nr. 4 AMG.

Trial locations and contacts

16 sites in 1 country.

16 sites in 1 country

Germany16 sites

  • Evangelische Lungenklinik Berlin

    Berlin, 13125

  • DRK Kliniken Berlin Mitte

    Berlin, 13359

  • Klinikum Chemnitz

    Chemnitz, 09116

  • Kliniken der Stadt Köln Krankenhaus Merheim

    Cologne, 51109

  • Universitätsklinikum Carl-Gustav-Carus

    Dresden, 01307

  • Klinikum Esslingen GmbH

    Esslingen am Neckar, 73730

  • Krankenhaus Nordwest

    Frankfurt am Main, 60488

  • LungenClinic Grosshansdorf

    Großhansdorf, 22927

  • Universitätsklinikum Heidelberg

    Heidelberg, 69126

  • Universitätsklinikum des Saarlandes

    Homburg/Saar, 66421

  • Klinikverbund Kempten-Oberallgäu

    Immenstadt im Allgäu, 87509

  • Klinik Löwenstein

    Löwenstein, 74245

  • Universitätsklinikum Mannheim

    Mannheim, 68167

  • Asklepios Fachkliniken München-Gauting

    München-Gauting, 82131

  • Klinikum Nürnberg

    Nuremberg, 90419

  • Universitätsklinikum Ulm

    Ulm, 89081

Other trials in Germany

About this study

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.

Read the detailed description

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

Being tested
Radiotherapy, Nivolumab
Keywords
Nivolumab, Radiotherapy
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Lung Neoplasms

What participants receive

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

  • RadiotherapyDrug

    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)

  • NivolumabDrug

    Nivolumab 240 mg fixed dose (q2w)

Study groups in NCT03044626
Study groupRoleWhat they receive
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)
Receives: Drug: Radiotherapy; Drug: 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).
Receives: Drug: Nivolumab

What is being measured

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

  1. objective response rate (ORR) according to RECIST 1.1 criteria

    Measured: through study completion, an average of 18 months

Secondary outcomes (6)

  1. progression free survival (PFS)

    Measured: approx. 6 months

  2. PFS using assessment according to irRECIST

    Immune-related Response Evaluation Criteria In Solid Tumors (irRECIST)

    Measured: approx. 6 months

  3. ORR using assessment according to irRECIST

    Immune-related Response Evaluation Criteria In Solid Tumors (irRECIST)

    Measured: approx. 6 months

  4. Overall Survival (OS)

    Measured: approx. 57 months

  5. Adverse Events

    Adverse Events: Type, incidence, and severity according to NCI CTCAE version 4.03

    Measured: approx. 36 months

  6. Assesment of Quality of life

    as determined with FACT-L (Functional Assessment of Cancer Therapy - Lung)

    Measured: approx. 57 months

Timeline

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

  1. First posted7 Feb 2017 (estimated)
  2. Study start10 Feb 2017
  3. Primary completion31 Dec 2020
  4. Study completion31 Dec 2020

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
101 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03044626
Sponsor's protocol ID
AIO-YMO/TRK-0415
Other IDs
2015-005741-31, CA209-430, 2015
Acronym
FORCE
Status last verified
Jan 2021
First submitted
5 Jan 2017
Last updated
13 Jan 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Bozorgmehr F, Chung I, Fischer JR, Bischof M, Atmaca A, Wetzel S, Faehling M, Bottke D, Wermke M, Troost EGC, Kropf-Sanchen C, Wiegel T, Schmidt B, Stupavsky A, Engel-Riedel W, Hammer-Hellmig M, Reinmuth N, Manapov F, Grohe C, Krempien R, Schumann C, Sterzing F, Reck M, Wurschmidt F, Fleckenstein J, Petroff A, Henschke S, Behnisch R, Cvetkovic J, Bruckner L, Schwab C, Stenzinger A, Gotze T, Kopp C, Schroder H, Debus J, Christopoulos P, Thomas M, Rieken S. Reconsidering palliative radiotherapy in addition to PD-1 blockade for non-small cell lung cancer: results from the FORCE phase II trial (AIO/YMO-TRK-0415). Clin Exp Metastasis. 2025 Jul 24;42(5):42. doi: 10.1007/s10585-025-10358-x.

    PubMed 40702361

  • Bozorgmehr F, Hommertgen A, Krisam J, Lasitschka F, Kuon J, Maenz M, Huber PE, Konig L, Kieser M, Debus J, Thomas M, Rieken S. Fostering efficacy of anti-PD-1-treatment: Nivolumab plus radiotherapy in advanced non-small cell lung cancer - study protocol of the FORCE trial. BMC Cancer. 2019 Nov 8;19(1):1074. doi: 10.1186/s12885-019-6205-0.

    PubMed 31703637

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Radiotherapy and Nivolumab in people with Carcinoma，Non-Small-Cell Lung and Metastatic Lung Cancer, run by AIO-Studien-gGmbH at 16 sites in Germany.

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 28 inclusion and 21 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 13 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in Germany. 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?

objective response rate (ORR) according to RECIST 1.1 criteria (time frame: through study completion, an average of 18 months). 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 NCT03044626, which also lists 2 linked publications.

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 13 Jan 2021.

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