ClinicalTrials.gg
TerminatedNCT03287947Updated Aug 9, 2022Results posted

LCI-GI-APX-NIN-001: Nintedanib in Metastatic Appendiceal Carcinoma

A Phase 2 interventional study of nintedanib in Appendix Cancer, sponsored by Wake Forest University Health Sciences. Terminated at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-08-09.

Sponsored by Wake Forest University Health Sciences · Phase 2, Interventional, and Treatment

Why this study was terminated
Low enrollment
Phase
Phase 2
Study type
Interventional
Enrollment
5
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study 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. 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.

02

Conditions studied

  • Appendix Cancer

Browse trials for

03

In context

Appendiceal Neoplasms

86 studies on the registry are indexed under Appendiceal Neoplasms; 25 are open to participants now.

This study's enrollment of 5 is below the median of 44 across 63 interventional studies indexed under Appendiceal Neoplasms.

Browse Appendiceal Neoplasms studies →

Lead sponsor

Wake Forest University Health Sciences is the lead sponsor of 1,351 studies on the registry; 201 are open to participants now.

Of its 332 completed or terminated interventional studies of FDA-regulated products, 251 (76%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

Subjects must meet all of the following criteria:

  1. Age at least 18 years old
  2. confirmed appendiceal carcinoma stage IV
  3. 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.
  4. at least 3 months
  5. performance status score 0-2
  6. Presence of measurable and/or evaluable, non- according to 1.1 criteria
  7. Written 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

Exclusion Criteria

Subjects must not meet any of the following criteria.

  1. Prior treatment with nintedanib or any other VEGFR inhibitor
  2. Known 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.
  3. 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.
  4. 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.
  5. Persistence of therapy related toxicity from previous chemo and/or radiotherapy as determined by the investigator.
  6. Active (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 .
  7. Radiographic evidence of cavitary or necrotic tumors.
  8. Tumors with radiographic evidence (CT or MRI) of local invasion of major blood vessels.
  9. Anti-neoplastic treatment for appendiceal cancer, with other drugs or treatment in another clinical trial within 30 days before start of study treatment.
  10. Therapeutic anticoagulation with drugs requiring monitoring (except low-dose heparin and/or heparin flush as needed for maintenance of an in-dwelling intravenous devise) or anti- therapy (except for low-dose therapy with acetylsalicylic acid less than or equal to 325mg per day).
  11. 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.
  12. History of clinically significant hemorrhagic or thromboembolic event in the past 6 months prior to consent.
  13. Known inherited predisposition to bleeding or thrombosis.
  14. Significant cardiovascular diseases (i.e. uncontrolled hypertension, unstable angina, history of infarction, congestive heart failure > II, serious cardiac arrhythmia, pericardial effusion) within the past 12 months prior to start of study treatment.
  15. Proteinuria grade 2 or greater.
  16. Creatinine > 1.5x or \< 45 ml/min.
  17. Hepatic function: total above normal limits; or AST > 1.5x ULN in subjects without liver . For subjects with liver metastasis: total bilirubin above normal limits; ALT or AST > 2.5x ULN.
  18. Coagulation parameters: International normalised ratio (INR) > 2x ULN, prothrombin time (PT) and partial thromboplastin time (PTT) > or equal to 1.5x ULN.
  19. (ANC) \< 1500/ml, platelets \< 100000/ml, \< 9.0 g/dl.
  20. Other at the time of signing the other than basal cell skin cancer or carcinoma in situ of the cervix.
  21. Active serious infections if requiring systemic antibiotic or antimicrobial therapy.
  22. Active or chronic and/or B infection.
  23. 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.
  24. 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.
  25. Sexually active women of and men who are sexually active with women of child-bearing potential and unwilling to use at least 2 medically acceptable methods of (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 for at least 2 years.
  26. 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.

Terms in these criteria, in plain language(27)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Histologically or cytologically confirmed

The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).

Your pathology report is the document that shows this.

Life expectancy

The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.

ECOG performance status

A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.

0
Fully active, no restrictions.
1
Limited in strenuous activity, but walking and able to do light work, such as housework or office work.
2
Walking and able to look after yourself, but unable to work; up and about more than half of waking hours.
3
Able to look after yourself only in part; in bed or a chair more than half of waking hours.
4
Unable to look after yourself at all; in bed or a chair all day.

Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.

Measurable disease

The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.

The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.

RECIST

The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.

“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Hypersensitivity

An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.

Clinically significant

Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.

Brain metastases

Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).

Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.

Leptomeningeal disease

Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.

Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.

Investigational drug or device

A drug or device being studied in a clinical trial.

It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.

INR, PT and aPTT (clotting tests)

Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.

Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.

Platelets

Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.

NYHA class (heart failure)

The New York Heart Association’s four classes of how much heart failure limits physical activity.

I
No limits: ordinary activity causes no undue tiredness or breathlessness.
II
Slight limits: comfortable at rest, ordinary activity causes symptoms.
III
Marked limits: comfortable at rest, less than ordinary activity causes symptoms.
IV
Symptoms even at rest; any activity makes them worse.

Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.

CTCAE grade

The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.

1
Mild.
2
Moderate.
3
Severe.
4
Life-threatening.
5
Death due to the event.

“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.

ULN (upper limit of normal)

The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.

“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.

GFR and eGFR (kidney filtering)

GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².

Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.

Bilirubin

A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.

Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.

ALT and AST (liver enzymes)

Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.

Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.

Metastases

Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.

Absolute neutrophil count (ANC)

The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.

It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.

Hemoglobin (Hb)

The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

Hepatitis C tests

Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.

After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.

Childbearing potential

Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).

Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

Postmenopausal

Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).

05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
5 participants (actual)

Study arms

  • Experimental
    A

    Nintedanib

    Drug: nintedanib

Interventions

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: From first dose of study drug to date of progression as determined by RECIST 1.1, assessed up to 7.5 months.

Secondary outcomes

  1. 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.

    Time frame: From date of first dose of study treatment to the date of death from any cause, assessed up to 14.5 months.

  2. 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.

    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.

  3. 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.

    Time frame: From the first dose of study drug to the last dose, assessed up to 7.5 months.

07

Results

Posted Jun 16, 2021

Participant flow

Participant flow — Overall Study
MilestoneNintedanib
Started5
Completed5
Not completed0

Outcome measures

PrimaryDisease 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.

Time frame:
From first dose of study drug to date of progression as determined by RECIST 1.1, assessed up to 7.5 months.
Reported as:
Number · Proportion of participants
Disease Control Rate
Proportion of participantsNintedanib
Disease Control Rate.25 (.0064 to .8058)
SecondaryOverall 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.

Time frame:
From date of first dose of study treatment to the date of death from any cause, assessed up to 14.5 months.
Reported as:
Median · months
Overall Survival
monthsNintedanib
Overall Survival2.62 (0.78 to 14.32)
SecondaryProgression-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.

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.
Reported as:
Median · months
Progression-free Survival
monthsNintedanib
Progression-free Survival1.34 (0.75 to 7.29)
SecondaryTreatment 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.

Time frame:
From the first dose of study drug to the last dose, assessed up to 7.5 months.
Reported as:
Mean · mg per cycle day
Treatment Administration of Nintedanib, as Measured by Average Daily Dose of Nintedanib.
mg per cycle dayNintedanib
Treatment Administration of Nintedanib, as Measured by Average Daily Dose of Nintedanib.350.4 ± 48.4

Adverse events

Collected over Adverse event data was collected for subjects from enrollment until 30 days after last dose of study drug, assessed up to 8.5 months. All-Cause Mortality data was collected from enrollment until death, assessed up to 14.5 months.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Nintedanib5/5 (100%)3/5 (60%)4/5 (80%)
Most frequent serious events
Most frequent serious events
EventNintedanib
Death NOSGeneral disorders1/5
Cardiac arrestCardiac disorders1/5
Duodenal obstructionGastrointestinal disorders1/5
Most frequent other events
Showing 10 of 16
Most frequent other events
EventNintedanib
AnorexiaMetabolism and nutrition disorders2/5
FatigueGeneral disorders2/5
NauseaGastrointestinal disorders2/5
VomitingGastrointestinal disorders2/5
Abdominal distensionGastrointestinal disorders1/5
Abdominal painGastrointestinal disorders1/5
Cardiac disorders - Other, BradycardiaCardiac disorders1/5
DehydrationMetabolism and nutrition disorders1/5
DiarrheaGastrointestinal disorders1/5
Dry skinSkin and subcutaneous tissue disorders1/5

Baseline characteristics

Five subjects enrolled to the study at their initiations of nintedanib therapy.

Age, Continuous
Age, Continuous(years)Nintedanib
Mean62.8 ± 15.8
Sex: Female, Male
Sex: Female, Male(Participants)Nintedanib
Female5
Male0
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Nintedanib
Hispanic or Latino0
Not Hispanic or Latino5
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Nintedanib
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American1
White4
More than one race0
Unknown or Not Reported0
Ascites present at baseline
Ascites present at baseline(Participants)Nintedanib
Count of participants1
08

Study locations

1 site
  • Levine Cancer Institute
    Charlotte, North Carolina 28204, United States
09

References and documents

Study documents

PDFs hosted by the registry, ClinicalTrials.gov.

10

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Ran from Nov 2017 to primary completion in Sep 2019, 21 months.

Results were first posted in Jun 2021, 1 year 9 months after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered
Jul 31, 2017
First posted
Sep 19, 2017
StartActual
Nov 10, 2017
Primary completionActual
Sep 3, 2019
CompletionActual
Oct 27, 2019
Results first posted
Jun 16, 2021
Last update
Aug 9, 2022
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Aug 9, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03287947
Responsible party
Sponsor
First posted
Sep 19, 2017
Start date
Nov 10, 2017
Primary completion
Sep 3, 2019
Completion
Oct 27, 2019
Results posted
Jun 16, 2021
Last update
Aug 9, 2022

Study contacts

Jimmy J Hwang, MD
principal investigator · Wake Forest University Health Sciences

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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Studies of the drug tested here: Nintedanib

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