NCT04046614
Completed
Phase 1
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
ConditionsAdenocarcinoma of the Lung
Interventionsnintedanib-nivolumab combination therapy
Overview
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- AIO-Studien-gGmbH
- Enrollment
- 56
- Locations
- 1
- Primary Endpoint
- Safety and tolerability as determined by frequency and severity of adverse events
Overview
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 Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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-
- •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.
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.
Arms & Interventions
nintedanib nivolumab
Experimental
nintedanib-nivolumab combination therapy
Intervention: nintedanib-nivolumab combination therapy (Drug)
Outcomes
Primary Outcomes
Safety and tolerability as determined by frequency and severity of adverse events
Time Frame: 47 months
Safety and tolerability as determined by frequency and severity of adverse events
progression free survival
Time Frame: 9 months
9 month progression free survival rate
Secondary Outcomes
- Overall response rate(35 months)
- Adverse events(47 months)
- Time to progression(35 months)
- Progression free survival(47 months)
- Depth of response(35 months)
- Overall survival(47 months)
- Time to response(35 months)
Investigators
Study Sites (1)
Loading locations...
Similar Trials
Completed
Phase 4
Safety and Tolerability Study of Pirfenidone in Combination With Nintedanib in Participants With Idiopathic Pulmonary Fibrosis (IPF)Idiopathic Pulmonary FibrosisNCT02598193Hoffmann-La Roche89
Completed
Phase 1
Combined Immunotherapy and Radiosurgery for Metastatic Colorectal CancerColorectal Neoplasms MalignantLiver MetastasesNCT03507699Sheba Medical Center19
Completed
Phase 1
ALT-803 Plus Nivolumab in Patients With Pretreated, Advanced or Metastatic Non-Small Cell Lung CancerNon-small Cell Lung CancerNCT02523469Medical University of South Carolina67
Active, not recruiting
Phase 1
Nintedanib and Azacitidine in Treating Participants With HOX Gene Overexpression Relapsed or Refractory Acute Myeloid LeukemiaAcute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2AFibroblast Growth Factor Basic Form MeasurementFLT3 Internal Tandem DuplicationRecurrent Adult Acute Myeloid LeukemiaRefractory Acute Myeloid LeukemiaNCT03513484Northwestern University44
Completed
Phase 1
A Study of Lenvatinib Plus Nivolumab in Participants With Hepatocellular CarcinomaCarcinoma, HepatocellularNCT03418922Eisai Co., Ltd.30