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Adenocarcinoma of the LungPhase 1/2NintNivoNCT04046614

Feasibility and Safety of Nintedanib in Combination With Nivolumab in Pretreated Patients With Advanced or Metastatic NSCLC of Adenocarcinoma Histology

A Phase 1/2 study testing nintedanib-nivolumab combination therapy in people with Adenocarcinoma of the Lung, run by AIO-Studien-gGmbH at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Determination of a safe dose for nintedanib+nivolumab combination therapy and the generation of exploratory efficacy data in pretreated patients with advanced or metastatic NSCLC of adenocarcinoma histology. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Adenocarcinoma of the Lung
What is being tested?
nintedanib-nivolumab combination therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
56 participants
Where
1 siteGermany
Study dates
25 May 2018to 15 Sep 2023
Phase
Phase 1/2
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

  • 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.
  • 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.
  • Age over or equal to 18 years at time of study entry.
  • Histologically confirmed adenocarcinoma of the lung stage IIIB/IV according to UICC7
  • One or two previous lines of systemic therapy including maintenance for advanced or metastatic NSCLC. Patients should be offered standard therapy regimens as recommended by current local Clinical Practice Guidelines. Neo-adjuvant and adjuvant therapies are permitted, provided that disease progression/relapse occurred more than 6 months after cessation of therapy.
  • ECOG performance status 0-1.
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  • Expected life expectancy of at least 3 months.
  • 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. If a potential target lesion has been irradiated previously, clear evidence of progression at target site must be documented.
  • A formalin fixed, paraffin-embedded (FFPE) tumor tissue block (archival or recent) or approx. of 10-15 unstained slides of tumor sample (slices must be recent and collected on slides provided by the sponsor) must be available for PD-L1 and other biomarker evaluation. Biopsy should be excisional, incisional or core needle. Fine needle aspiration is insufficient.
  • Prior therapies and surgeries are allowed if completed 2 weeks (for minor surgery) or 4 weeks (palliative radiotherapy for bone pain; major surgeries with complete wound healing), respectively prior to start of treatment and patient recovered from toxic effects.
  • Adequate blood count, liver-enzymes, and renal function (obtained no later than 14 days prior to start of treatment)
  • Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 5 months (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of nivolumab. Since the effect of nintedanib on the metabolism and efficacy of contraceptives has not been investigated, barrier methods should be applied as a second form of contraception, to avoid pregnancy.
  • Women of childbearing potential must have a negative serum or urine pregnancy test within 24 hours prior to the start of study treatment and monthly throughout treatment until 5 months after last dose of IMP.
  • 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 7 months 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

  • More than one or two prior treatment lines for advanced or metastatic NSCLC
  • Subjects with active CNS metastases are excluded. Subjects are eligible if CNS metastases are adequately treated and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 4 weeks prior to enrollment. In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent).)
  • Leptomeningeal disease, carcinomatous meningitis, chronic diarrhea or short bowel syndrome
  • Known activating EGFR mutation or a known ALK translocation.
  • Patients with symptomatic interstitial lung disease.
  • Any previous treatment with nitedanib, ramucirumab, anti-tumor vaccines or other immuno-stimulatory antitumor agents exept checkpoint inhibitors.
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  • Ongoing toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue that have not resolved to grade 1 (NCI CTCAE version 4.03) or baseline before administration of study drug.
  • Major injuries within the past 4 weeks prior to start of study treatment with incomplete wound healing and/or planned surgery during the on-treatment study period.
  • Patients should be excluded if they have an active, known or suspected autoimmune disease or history of allogeneic tissue/solid organ transplant. 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.
  • Positive test for HBV sAg or HCV RNA indicating acute or chronic infection OR positive HIV test
  • History of severe hypersensitivity reactions to other monoclonal antibodies or any excipient. Known hypersensitivity to nintedanib, peanut, soya or to any of the excipients or contrast media.
  • Radiotherapy to the target lesion within the past 3 months prior to baseline imaging. (see also inclusion criterion 8)
  • Radiographic evidence of cavitary or necrotic tumors
  • Centrally located tumors with radiographic evidence (CT or MRI) of local invasion of major blood vessels
  • Therapeutic anticoagulation with drugs requiring INR monitoring (except low-dose heparin and/or heparin flush as needed for maintenance of an in-dwelling intravenous devise) or anti-platelet therapy (except for low-dose therapy with acetylsalicylic acid < 325mg per day)
  • History of clinically significant hemorrhagic or thromboembolic event in the past 6 months
  • Known inherited predisposition to bleeding or thrombosis
  • Significant cardiovascular diseases ( i.e. uncontrolled hypertension, unstable angina, history of infarction within the past 12 months prior to start of study treatment, congestive heart failure > NYHA II, serious cardiac arrhythmia, pericardial effusion)
  • Active alcohol or drug abuse
  • Body Mass Index (BMI) exceeding 20 kg/m2
  • 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.
  • 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) ≤28 days prior to the first dose of study treatment.
  • Any other serious or uncontrolled medical disorder (e.g. active ulcers), 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.
  • 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

1 site in 1 country.

Germany1 site

  • LungenClinic Grosshansdorf

    Großhansdorf

Other trials in Germany

About this study

Official title: Feasibility and Safety of Nintedanib in Combination With Nivolumab in Pretreated Patients With Advanced or Metastatic NSCLC of Adenocarcinoma Histology - An AIO Phase Ib Trial

Determination of a safe dose for nintedanib+nivolumab combination therapy and the generation of exploratory efficacy data in pretreated patients with advanced or metastatic NSCLC of adenocarcinoma histology.

Being tested
nintedanib-nivolumab combination therapy
Medical subject headings
Adenocarcinoma of Lung

What participants receive

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

  • nintedanib-nivolumab combination therapyDrug

    Safety run-in - Dose finding stage The safety-run in phase will be designed as a standard 3+3 design for dose escalation/de-escalation and 3 to 6 patients will be enrolled in each cohort sequentially, depending on occurrence of dose limiting toxicities. The recommended phase 2 dose (RP2D) will be the highest dose in which the frequency of DLTs is less than 33% if no other safety or feasibility considerations prevail.

    Expansion phase: Nintedanib RP2D + nivolumab 240 mg Q2W until progression of disease.

Study groups in NCT04046614
Study groupRoleWhat they receive
nintedanib nivolumabExperimentalnintedanib-nivolumab combination therapy
Receives: Drug: nintedanib-nivolumab combination therapy

What is being measured

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

  1. Safety and tolerability as determined by frequency and severity of adverse events

    Safety and tolerability as determined by frequency and severity of adverse events

    Measured: 47 months

  2. progression free survival

    6-month progression free survival rate

    Measured: 6 months

  3. progression free survival

    9 month progression free survival rate

    Measured: 9 months

Secondary outcomes (7)

  1. Overall response rate

    Determination of the overall response rate

    Measured: 35 months

  2. Progression free survival

    Determination of progression free survival

    Measured: 47 months

  3. Time to progression

    Determination of the time to progression

    Measured: 35 months

  4. Overall survival

    Determination of the overall survival

    Measured: 47 months

  5. Adverse events

    Determination of adverse events, sevier adverse events, treatment emergent adverse events according to common terminology criteria of adverse events version 4.03

    Measured: 47 months

  6. Depth of response

    Determination of depth of response defined by the maximal tumor shrinkage before progression. Depth of response will be assessed by tumor imaging (computed tomography or magnetic resonance tomography) evaluated according to Response Evaluation Criteria in Solid Tumors version 1.1

    Measured: 35 months

  7. Time to response

    Determination time to response

    Measured: 35 months

Timeline

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

  1. First posted6 Aug 2019
  2. Study start25 May 2018
  3. Primary completion23 May 2023
  4. Study completion15 Sep 2023

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
56 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04046614
Sponsor's protocol ID
AIO-TRK-0117
Acronym
NintNivo
Status last verified
Feb 2024
First submitted
21 Mar 2018
Last updated
6 Feb 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing nintedanib-nivolumab combination therapy in people with Adenocarcinoma of the Lung, run by AIO-Studien-gGmbH at 1 site 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 14 inclusion and 28 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 6 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

Safety and tolerability as determined by frequency and severity of adverse events (time frame: 47 months). The study lists 3 primary outcomes in all. 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 NCT04046614.

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 6 Feb 2024.

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