Appendix CancerPhase 2NCT03287947
LCI-GI-APX-NIN-001: Nintedanib in Metastatic Appendiceal Carcinoma
A Phase 2 study testing nintedanib in people with Appendix Cancer, run by Wake Forest University Health Sciences at 1 site in United States.
Trial summary
The purpose of this trial is to evaluate the disease control rate of nintedanib in subjects with metastatic appendiceal cancer for whom initial fluoropyrimidine-based chemotherapy has failed. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Appendix Cancer
- What is being tested?
- nintedanib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Nov 2017to 27 Oct 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Levine Cancer Institute
Charlotte, North Carolina, 28204
About this study
The purpose of this trial is to evaluate the disease control rate of nintedanib in subjects with metastatic appendiceal cancer for whom initial fluoropyrimidine-based chemotherapy has failed. Based on previous studies, the anticancer activity of nintedanib in lung and ovarian cancer trials, along with the similarities between appendiceal and colorectal cancer and potentially ovarian cancer, warrant additional investigation for the optimal treatment of metastatic appendiceal carcinomas.
Read the detailed description
The primary study objective is to evaluate the disease control rate. The secondary study objectives are to evaluate safety and toxicity, objective response rate, overall and 6-month progression free survival, and overall survival. Exploratory study objectives include evaluation of serum and ascites VEGF, hypertension, and paracentesis frequency in subjects with ascites at study entry.
- Conditions
- Appendix Cancer
- Being tested
- nintedanib
- Medical subject headings
- Appendiceal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
nintedanibDrug
Oral nintedanib, taken twice daily
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | Nintedanib Receives: Drug: nintedanib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease Control Rate
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.
Measured: From first dose of study drug to date of progression as determined by RECIST 1.1, assessed up to 7.5 months.
Secondary outcomes (3)
Overall Survival
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.
Measured: 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
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.
Measured: 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.
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.
Measured: From the first dose of study drug to the last dose, assessed up to 7.5 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2017
- Study start10 Nov 2017
- Primary completion3 Sep 2019
- Study completion27 Oct 2019
Why it stopped: Low enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Appendix CancerStudies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single arm phase 2 study.
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- Boehringer Ingelheim
- Responsible party
- Sponsor
- Investigators
- Jimmy J Hwang, MD, Principal investigator, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03287947
- Sponsor's protocol ID
- LCI-GI-APX-NIN-001
- Other IDs
- 00021617
- Status last verified
- Jan 2022
- First submitted
- 31 Jul 2017
- Last updated
- 9 Aug 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- LCI-GI-APX-NIN-001: Nintedanib in Metastatic Appendiceal Carcinoma
- ClinicalTrials.gov ID
- NCT03287947
- Acronym / sponsor ID
- LCI-GI-APX-NIN-001
- Conditions
- Appendix Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low enrollment
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Collaborators
- Boehringer Ingelheim
- Study start
- 10 Nov 2017 (actual)
- Primary completion
- 3 Sep 2019 (actual)
- Study completion
- 27 Oct 2019 (actual)
- First posted
- 19 Sep 2017 (actual)
- Results
- Posted 16 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this trial is to evaluate the disease control rate of nintedanib in subjects with metastatic appendiceal cancer for whom initial fluoropyrimidine-based chemotherapy has failed. Based on previous studies, the anticancer activity of nintedanib in lung and ovarian cancer trials, along with the similarities between appendiceal and colorectal cancer and potentially ovarian cancer, warrant additional investigation for the optimal treatment of metastatic appendiceal carcinomas.
Detailed description
The primary study objective is to evaluate the disease control rate. The secondary study objectives are to evaluate safety and toxicity, objective response rate, overall and 6-month progression free survival, and overall survival. Exploratory study objectives include evaluation of serum and ascites VEGF, hypertension, and paracentesis frequency in subjects with ascites at study entry.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single arm phase 2 study.
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Drug: nintedanibNintedanib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (30 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| nintedanibOral nintedanib, taken twice daily | Drug | A |
Primary outcome
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.
3 secondary outcomes
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.
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.
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jimmy J Hwang, MD principal investigator
Wake Forest University Health Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing nintedanib in people with Appendix Cancer, run by Wake Forest University Health Sciences at 1 site in United States.
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 8 inclusion and 30 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: stopped early, as of the sponsor's last update on 9 Aug 2022. 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 United States. 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 phase mean?
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?
Yes. Results are posted in the registry (first posted 16 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Aug 2022.