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

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Brief Title

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

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

Brief 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.
    


Study Phase

Phase 1/Phase 2

Study Type

Interventional


Primary Outcome

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

Secondary Outcome

 Overall response rate

Condition

Adenocarcinoma of the Lung

Intervention

nintedanib-nivolumab combination therapy

Study Arms / Comparison Groups

 nintedanib nivolumab
Description:  nintedanib-nivolumab combination therapy

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

62

Start Date

May 25, 2018

Completion Date

April 3, 2022

Primary Completion Date

July 3, 2021

Eligibility Criteria

        Inclusion Criteria:

          -  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.

          -  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.

        Exclusion Criteria:

          -  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.

          -  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.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Martin Reck, Prof. Dr., +49 30 8145344, [email protected]

Location Countries

Germany

Location Countries

Germany

Administrative Informations


NCT ID

NCT04046614

Organization ID

AIO-TRK-0117


Responsible Party

Sponsor

Study Sponsor

AIO-Studien-gGmbH


Study Sponsor

Martin Reck, Prof. Dr., Principal Investigator, LungenClinic Grosshansdorf GmbH


Verification Date

August 2019