Study Stopped
low accrual
Nintedanib Compared With Placebo in Treating Against Radiation-Induced Pneumonitis in Patients With Non-small Cell Lung Cancer That Cannot Be Removed by Surgery and Are Undergoing Chemoradiation Therapy
A Phase II Randomized, Double-Blind, Placebo-Controlled Study Evaluating Nintedanib Versus Placebo as Prophylaxis Against Radiation Pneumonitis in Patients With Unresectable NSCLC Undergoing Chemoradiation Therapy
3 other identifiers
interventional
8
1 country
1
Brief Summary
This trial studies the side effects and how well nintedanib works compared to a placebo in treating against radiation-induced pneumonitis (inflammation of the lungs) in patients with non-small cell lung cancer that cannot be removed by surgery and are undergoing chemoradiation therapy. Nintedanib may help shrink or slow the growth of radiation-induced pneumonitis by blocking some of the enzymes needed for cells to grow and may prevent the growth of new blood vessels. It may also help reduce the recurrence of non-small cell lung cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Jun 2015
Typical duration for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 20, 2015
CompletedFirst Posted
Study publicly available on registry
May 22, 2015
CompletedStudy Start
First participant enrolled
June 29, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 10, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
June 10, 2019
CompletedResults Posted
Study results publicly available
April 6, 2020
CompletedApril 6, 2020
March 1, 2020
4 years
May 20, 2015
March 6, 2020
March 23, 2020
Conditions
Outcome Measures
Primary Outcomes (1)
Portion of Common Terminology Criteria for Adverse Events Grade 2 or Higher Radiation Pneumonitis
Will compare the rate of symptomatic radiation pneumonitis in patients who received nintedanib versus placebo. Assessed using the intent-to-treat principle and a one-sided exact test about the Cochran-Mantel-Haenszel correlation and regression test. The grade 2 or higher radiation penumonitis is identified by the Common Terminology Criteria for Adverse Events.
At 6 months after completion of chemoradiation
Secondary Outcomes (8)
Number of Participants With Adverse Events, Graded According to Common Terminology Criteria for Adverse Events Version 4.0
Up to 2.5 years post-treatment
Overall Survival
1 year survival, with follow-up assessed up to 2.5 years post-treatment
Progression-free Survival
1 year progression-free survival, with follow-up assessed up to 2.5 years post-treatment
Percent Changes in Overall Quality of Life and Symptom Scores
Baseline up to 2.5 years post-treatment
Percent Change in Pulmonary Function Tests
Baseline up to 2.5 years post-treatment
- +3 more secondary outcomes
Study Arms (3)
Arm I (nintedanib)
EXPERIMENTALBeginning 4-8 weeks after completion of radiation therapy, patients receive nintedanib PO BID on days 1-28. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
Arm II (placebo)
PLACEBO COMPARATORBeginning 4-8 weeks after completion of radiation therapy, patients receive placebo capsules PO BID on days 1-28. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
Arm III (nintedanib, durvalumab)
EXPERIMENTALBeginning 4-8 weeks after completion of radiation therapy, patients receive nintedanib PO BID on days 1-28 and standard of care durvalumab IV over 60 minutes on days 1 and 15. Treatment with nintedanib repeats every 28 days for up to 6 cycles and treatment with durvalumab repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.
Interventions
Given IV
Given PO
Ancillary studies
Eligibility Criteria
You may qualify if:
- Histologically or cytologically-proven non squamous cell NSCLC; mixed histology with small cell lung carcinoma (SCLC) component not allowed
- Patients with stage II ? IV non squamous cell NSCLC who received at least 54 Gy of total planned thoracic radiation dose will be eligible; patients must have received at least one cycle of chemotherapy concurrently during the course of thoracic radiation; regimens allowed are platinum combinations with either etoposide or a taxane regardless of histology subtype; platinum with pemetrexed for patients with non-squamous NSCLC only; patients with oligometastatic stage IV cancer are eligible if they have received only one line of systemic therapy for their stage IV cancer prior to the concurrent chemoradiation phase
- Patient must have had a complete response (CR)/partial response (PR)/stable disease (SD), 4-6 weeks after completing last fraction of radiation therapy
- Eastern Cooperative Oncology Group (ECOG) performance score 0-2
- Absolute neutrophil count (ANC) \>= 1,500/uL
- Platelet count \>= 100,000/uL
- Hemoglobin \>= 9 g/dL
- Total bilirubin =\< normal or for those with Gilbert?s syndrome =\< 1.5 times upper limit of normal (ULN) OR direct bilirubin normal (per institute standards)
- Aspartate aminotransferase (AST) =\< 1.5 x ULN; alanine aminotransferase (ALT) and AST =\< 2.5 x ULN is acceptable if there is liver metastasis
- Fertile patients must use adequate contraception
You may not qualify if:
- Whole-brain radiotherapy (WBRT) \< 14 days from the anticipated start of nintedanib/placebo administration
- Squamous cell NSCLC
- Unable to start nintedanib/placebo treatment between 4-8 weeks after completing the last dose of thoracic radiation
- Active untreated brain or leptomeningeal metastases; in patients with treated central nervous system (CNS) metastases, eligible if symptoms controlled for at least 4 weeks; dexamethasone allowed if total daily dose does not exceed 2 mg
- Major injuries or surgery (e.g., craniotomy) \< 28 days from the start of nintedanib/placebo administration; wound should be healed prior to starting therapy
- Second malignancies are allowed as long as the disease does not require active treatment with concomitant systemic cytotoxic chemotherapy, investigational or biologic therapy (e.g., anti-cytotoxic T-lymphocyte-associated protein 4 \[CTLA4\] or human epidermal growth factor receptor 2 \[HER2\] monoclonal antibodies); hormone-related therapies (e.g., gonadotrophin releasing hormone (LHRH) agonists, tamoxifen, etc.) are allowed
- Concurrent uncontrolled illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would increase the risk associated with study participation and/or limit compliance with study requirements
- Inability to swallow study medication
- Presence of active malabsorption disorder (e.g., flare episodes documented within the preceding 3 months, presence of symptoms requiring daily medications for control) or history of extensive small bowel resection
- Known bleeding or thrombotic diathesis
- History of arterial or venous thromboembolic event within 12 months prior to study participation
- Active hemoptysis or history of clinically relevant hemoptysis as determined by the treating physician; patients who had history of transient minor hemoptysis after bronchoscopic biopsy are eligible unless deemed otherwise by the treating physician
- Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or higher proteinuria
- Investigational agent administered \< 28 days prior to treatment with nintedanib. Last dose of systemic chemotherapy administered \< 14 days prior to treatment with nintedanib
- Known chronic active hepatitis B or hepatitis C; human immunodeficiency virus (HIV)-positive patients receiving or are candidates for antiretroviral therapy are also excluded
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Roswell Park Cancer Institutelead
- National Cancer Institute (NCI)collaborator
Study Sites (1)
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Related Publications (1)
Rimner A, Moore ZR, Lobaugh S, Geyer A, Gelblum DY, Abdulnour RE, Shepherd AF, Shaverdian N, Wu AJ, Cuaron J, Chaft JE, Zauderer MG, Eng J, Riely GJ, Rudin CM, Els NV, Chawla M, McCune M, Li H, Jones DR, Sopka DM, Simone CB 2nd, Mak R, Weinhouse GL, Liao Z, Gomez DR, Zhang Z, Paik PK. Randomized Phase 2 Placebo-Controlled Trial of Nintedanib for the Treatment of Radiation Pneumonitis. Int J Radiat Oncol Biol Phys. 2023 Aug 1;116(5):1091-1099. doi: 10.1016/j.ijrobp.2023.02.030. Epub 2023 Mar 7.
PMID: 36889516DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- CTRP/CT.gov Registry Coordnator
- Organization
- Roswell Park
Study Officials
- PRINCIPAL INVESTIGATOR
Grace K Dy
Roswell Park Cancer Institute
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- SUPPORTIVE CARE
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 20, 2015
First Posted
May 22, 2015
Study Start
June 29, 2015
Primary Completion
June 10, 2019
Study Completion
June 10, 2019
Last Updated
April 6, 2020
Results First Posted
April 6, 2020
Record last verified: 2020-03