- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03287947
LCI-GI-APX-NIN-001: Nintedanib in Metastatic Appendiceal Carcinoma
Study Overview
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
North Carolina
-
Charlotte, North Carolina, United States, 28204
- Levine Cancer Institute
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria
Subjects must meet all of the following criteria:
- Age at least 18 years old
- Histologically confirmed appendiceal carcinoma stage IV
- Failure of initial fluoropyrimidine -based chemotherapy. Failure is defined as progression on or within 6 months of last day of therapy or intolerance of initial fluoropyrimidine-based chemotherapy.
- Life expectancy at least 3 months
- ECOG performance status score 0-2
- Presence of measurable and/or evaluable, non-measurable disease according to RECIST 1.1 criteria
- Written informed consent signed and dated by subject or Legally Authorized Representative (LAR) prior to admission to the study in accordance with ICH-GCP guidelines and to the local legislation.
Exclusion Criteria
Subjects must not meet any of the following criteria.
- Prior treatment with nintedanib or any other VEGFR inhibitor
- Known hypersensitivity to peanut or soya or to contrast media. History of hypersensitivity to contrast media is allowed if the subject is able to tolerate contrast media with pre-medication.
- Chemo-, hormone-, radio-(except for brain and extremities) or immunotherapy, or therapy with monoclonal antibodies or small tyrosine kinase inhibitors within the past 4 weeks prior to treatment with the trial drug.
- Radiotherapy to any target lesion within the past 3 months prior to baseline imaging when that target lesion is the only target lesion identified on baseline imaging, unless it has subsequently grown.
- Persistence of clinically relevant therapy related toxicity from previous chemo and/or radiotherapy as determined by the investigator.
- Active brain metastases (e.g. stable for <4 weeks, no adequate previous treatment with radiotherapy, symptomatic, requiring treatment with anti-convulsants; dexamethasone therapy will be allowed if administered as stable dose for at least one month) or leptomeningeal disease.
- Radiographic evidence of cavitary or necrotic tumors.
- Tumors with radiographic evidence (CT or MRI) of local invasion of major blood vessels.
- Anti-neoplastic treatment for appendiceal cancer, with other investigational drugs or treatment in another clinical trial within 30 days before start of study treatment.
- 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 less than or equal to 325mg per day).
- Major injuries and/or surgery within the past 4 weeks prior to start of study treatment, incomplete wound healing or planned surgery during the on-treatment study period.
- History of clinically significant hemorrhagic or thromboembolic event in the past 6 months prior to consent.
- Known inherited predisposition to bleeding or thrombosis.
- Significant cardiovascular diseases (i.e. uncontrolled hypertension, unstable angina, history of infarction, congestive heart failure > NYHA II, serious cardiac arrhythmia, pericardial effusion) within the past 12 months prior to start of study treatment.
- Proteinuria CTCAE grade 2 or greater.
- Creatinine > 1.5x ULN or GFR < 45 ml/min.
- Hepatic function: total bilirubin above normal limits; ALT or AST > 1.5x ULN in subjects without liver metastasis. For subjects with liver metastasis: total bilirubin above normal limits; ALT or AST > 2.5x ULN.
- Coagulation parameters: International normalised ratio (INR) > 2x ULN, prothrombin time (PT) and partial thromboplastin time (PTT) > or equal to 1.5x ULN.
- Absolute neutrophil count (ANC) < 1500/ml, platelets < 100000/ml, Hemoglobin < 9.0 g/dl.
- Other malignancies at the time of signing the informed consent other than basal cell skin cancer or carcinoma in situ of the cervix.
- Active serious infections if requiring systemic antibiotic or antimicrobial therapy.
- Active or chronic hepatitis C and/or B infection.
- Gastrointestinal disorders (like chronic diarrhea) or abnormalities that would interfere with absorption of the study drug. Subjects with this disorder may be allowed if able to tolerate anti-diarrheal medications like loperamide.
- Serious illness or concomitant non-oncological disease such as neurologic, psychiatric, infectious disease or active ulcers (gastro-intestinal tract, skin) or laboratory abnormality that may increase the risk associated with study participation or study drug administration and in the judgment of the investigator would make the subject inappropriate for entry into the study.
- Sexually active women of child-bearing potential and men who are sexually active with women of child-bearing potential and unwilling to use at least 2 medically acceptable methods of contraception (e.g. such as implants, injectables, combined oral contraceptives, some intrauterine devices or vasectomized partner for participating females, condoms for participating males) during the trial and for at least three months after end of active therapy. Female subjects will be considered of child-bearing potential unless surgically sterilized by hysterectomy or bilateral tubal/salpingectomy, or post-menopausal for at least 2 years.
- Pregnancy or breast feeding; female participants of child-bearing potential must have a negative pregnancy test (B-HCG test in urine or serum) before commencing study treatment.
aa. Psychological, familial, sociological, or geographical factors potentially hampering compliance with the study protocol and follow-up schedule per the investigator.
bb. Alcohol or drug abuse which in the determination of the investigator would interfere with trial participation.
cc. Significant weight loss (> 10% of baseline weight) within past 2 months prior to consenting for the trial. Removal of ascites should not be calculated as weight loss.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: A
Nintedanib
|
Oral nintedanib, taken twice daily
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Disease Control Rate
Time Frame: From first dose of study drug to date of progression as determined by RECIST 1.1, assessed up to 7.5 months.
|
The disease control rate is the proportion of those subjects with complete response, partial response, or stable disease, as defined by Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1).
Per RECIST 1.1 criteria for target lesions assessed by radiologic evaluation of CT and tumor measurements: Complete Response (CR), Disappearance of all target and non-target lesions, any pathological lymph nodes reduced in short axis to <10 mm; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor PD; Disease Control Rate (DCR) = CR + PR + SD.
|
From first dose of study drug to date of progression as determined by RECIST 1.1, assessed up to 7.5 months.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival
Time Frame: From date of first dose of study treatment to the date of death from any cause, assessed up to 14.5 months.
|
Overall survival was defined as the duration from the start of nintedanib treatment to the date of death from any cause; subjects who are alive or lost to follow-up at the time of the analysis were censored at the last known date they were alive.
Median overall survival was estimated using Kaplan-Meier methods.
No formal comparative statistical analysis of overall survival was performed due to low accrual.
|
From date of first dose of study treatment to the date of death from any cause, assessed up to 14.5 months.
|
Progression-free Survival
Time Frame: From date of first dose of study treatment to the date of progressive disease or death from any cause, whichever occurred first, assessed up to 7.5 months.
|
Progression-free survival was defined as the duration from the start of nintedanib treatment to the first occurrence of either progressive disease or death; disease progression was objectively determined per Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1) or subjectively determined by the investigator.
Per RECIST 1.1 criteria for target lesions assessed by radiologic evaluation of CT and tumor measurements: Progressive Disease (PD), >= 20% increase in the sum of the longest diameter of target lesions (at least 5 mm), or a measurable increase or progression in a non-target lesion, or the appearance of new lesions.
Median progression-free survival was estimated using Kaplan-Meier methods.
No formal comparative statistical analysis of progression-free survival was performed due to low accrual.
|
From date of first dose of study treatment to the date of progressive disease or death from any cause, whichever occurred first, assessed up to 7.5 months.
|
Treatment Administration of Nintedanib, as Measured by Average Daily Dose of Nintedanib.
Time Frame: From the first dose of study drug to the last dose, assessed up to 7.5 months.
|
The average daily dose of nintedanib is calculated as the total cumulative dose (in mg) of nintedanib administered divided by the number of 28-day cycles on nintedanib treatment.
Prescribed daily dose of nintedanib is 400 mg.
|
From the first dose of study drug to the last dose, assessed up to 7.5 months.
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Jimmy J Hwang, MD, Wake Forest University Health Sciences
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms
- Neoplasms by Site
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Cecal Diseases
- Cecal Neoplasms
- Appendiceal Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Nintedanib
Other Study ID Numbers
- LCI-GI-APX-NIN-001
- 00021617 (Other Identifier: Advarra IRB)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Appendix Cancer
-
Turku University HospitalOulu University Hospital; Kuopio University Hospital; Seinajoki Central Hospital and other collaboratorsNot yet recruitingAppendicitis | Appendix Cancer | Appendix Mass | Appendix Abscess | Appendix Nec | Appendix Tumor | Appendix Diseases
-
Andreana Holowatyj, PhD, MSCIRecruitingAppendix Cancer | Appendiceal Neoplasms | Appendix Adenocarcinoma | Appendiceal Cancer | Appendiceal Adenocarcinoma | Appendix Tumor | Appendiceal Mucinous Neoplasm | Appendiceal Carcinoid Tumor | Appendiceal Neoplasm Malignant Secondary | Appendix Mucinous Neoplasm | Appendix Cancer Metastatic | Appendix NET | Low-Grade Appendix Mucinous Neoplasm and other conditionsUnited States
-
Hanyang UniversityCompletedAppendix, UltrasonographyKorea, Republic of
-
Zhongshan Hospital Xiamen UniversityActive, not recruitingColonoscopy | Gastrointestinal Microbiome | Appendix | Carbon Dioxide InsufflationChina
-
Laval UniversityCiusss de L'Est de l'Île de MontréalRecruitingColorectal Cancer | Peritoneal Carcinomatosis | Peritoneal Metastases | Appendix Cancer | Appendix NeoplasmCanada
-
Saglik Bilimleri UniversitesiNot yet recruitingPediatric ALL | Appendix DiseasesTurkey
-
Hillel Yaffe Medical CenterUnknown
-
Wake Forest University Health SciencesNational Cancer Institute (NCI)CompletedPrimary Peritoneal Cavity Cancer | Carcinoma of the AppendixUnited States
-
City of Hope Medical CenterNational Cancer Institute (NCI)RecruitingPeritoneal Carcinomatosis | Stage IV Uterine Corpus Cancer AJCC v8 | Stage IVA Uterine Corpus Cancer AJCC v8 | Stage IVB Uterine Corpus Cancer AJCC v8 | Metastatic Malignant Solid Neoplasm | Malignant Uterine Neoplasm | Clinical Stage IV Gastric Cancer AJCC v8 | Metastatic Colorectal Carcinoma | Stage... and other conditionsUnited States
-
Milton S. Hershey Medical CenterCompletedEndometriosis of the AppendixUnited States
Clinical Trials on nintedanib
-
Boehringer IngelheimCompletedCarcinoma, HepatocellularJapan
-
Boehringer IngelheimCompleted
-
Boehringer IngelheimCompletedHealthyUnited Kingdom
-
Sixth Affiliated Hospital, Sun Yat-sen UniversityNot yet recruiting
-
Boehringer IngelheimCompletedIdiopathic Pulmonary FibrosisSpain, Korea, Republic of, Belgium, Czechia, Australia, Germany, United Kingdom, United States, France, Finland, Japan, Poland, Hungary
-
Boehringer IngelheimApproved for marketingIdiopathic Pulmonary FibrosisUnited States
-
Boehringer IngelheimActive, not recruitingLung Diseases, InterstitialUnited States, Spain, United Kingdom, Canada, Finland, Norway, Italy, Argentina, Belgium, Brazil, Czechia, France, Greece, Mexico, Poland, Germany, Portugal
-
Boehringer IngelheimNo longer availableLung Diseases, Interstitial (in Pediatric Populations) | Childhood Interstitial Lung Disease (chILD)
-
Boehringer IngelheimNo longer availableIdiopathic Pulmonary FibrosisBrazil
-
Boehringer IngelheimActive, not recruitingLung Diseases, InterstitialChina