ClinicalTrials.gg
Active, not recruitingNCT05797246Updated Nov 3, 2026

Bevacizumab in Adults With Recurrent Respiratory Papillomatosis (RRP)

A Phase 2 interventional study of Bevacizumab in Respiratory Tract Diseases, Neoplasms and Neoplasms by Histologic Type, sponsored by National Cancer Institute (NCI). Active, not recruiting at 1 site in United States. Open to participants aged 18 Years to 120 Years. Per ClinicalTrials.gov, last updated 2026-11-03.

Primary conditionRespiratory Tract InfectionsRegistry: Respiratory Tract DiseasesReclassifiedWhy we changed it
Registry
Respiratory Tract Diseases — the first condition term the registry derived for this study.
ClinicalTrials.gg
Respiratory Tract Infections
Why
  1. The study's listed conditions name Respiratory Tract Infections, a narrower term within Respiratory Tract Diseases.
Confidence
High: the new condition is named in the study's own listed conditions. Of 351 hand-checked studies reclassified this way, 68% were exactly right and 84% in the right disease family; the registry's first term was right for 5% (measured 2026-10-21). How we classify →
Wrong?
Tell us the study's main condition →

Sponsored by National Cancer Institute (NCI) · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
21
Allocation
Non-randomized
Ages
18 Years to 120 Years
Sex
All
01

Where this study stands

Counted across the records on this site · 2026-11-12

Among 209 studies in Respiratory Tract Infections with a site in United States — 20 open to participants now, 27 under way, 5 of them phase 3. Respiratory Tract Infections · United States.

Enrollment
143rd of 159
21 · median 134
Started
2023
with 13 others
Phase 2
31 of 209
1 open now
Primary completion
2027-07
later than 13 of 25 live
Registered
175th of 209
by date

Among the 209 studies in Respiratory Tract Infections with a site in United States, this one is the 143rd largest by enrollment of the 159 interventional ones, is one of 14 that started in 2023, is one of 31 in phase 2, reaches primary completion later than 13 of the 25 other live ones, and was the 175th registered.

By phase

209 studies; the count open now beside each. This study's row is marked.

No phase65 · 8 open
Observational48 · 4 open
Phase 2this study31 · 1 open
Phase 120 · 1 open
Phase 320 · 5 open
Phase 414 · 1 open
Phase 1/29 · 0 open
Phase 2/32 · 0 open

By the year they started

First in 1997; this study’s year is marked. 14 started in 2023.

Size and results

Median enrollment 134 across the 159 interventional studies, 558 across the 48 observational. Of the 172 that completed or were terminated, 67 (39%) have results posted.

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Watch this landscapeDownload CSVWith an account: a weekly mail of what changed among 209 studies in Respiratory Tract Infections with a site in United States, or all of them as a file.
02

Study summary

Background:

Recurrent respiratory papillomatosis (RRP) is a rare disease that causes wart-like growths in the airways. These growths come back when removed; some people may need 2 or more surgeries per year to keep their airways clear. Better treatments are needed.

Objective:

To see if a drug called bevacizumab can reduce the number of surgeries needed in people with RRP.

Eligibility:

People aged 18 and older with recurrent RRP; they must need surgery to remove the growths in their airways.

Design:

Participants will be screened. Their ability to breathe and speak will be evaluated. They will have an endoscopy: a flexible tube with a light and camera will be inserted into their nose and throat. They will have a test of their heart function and imaging scans of their chest.

Participants will have surgery to remove the growths in their airways.

Bevacizumab is given through a small tube placed in a vein in the arm. After the surgery, participants will receive 11 doses of this drug: every 3 weeks for 3 doses, and then every 6 weeks for 8 more doses. They will come to the clinic for each dose; each visit will be about 8 hours.

Tissue samples of the growths will be collected after the second treatment; this will be done under general anesthesia.

Participants may undergo apheresis: Blood will be drawn from a needle in an arm. The blood will pass through a machine that separates out the cells needed for the study. The remaining blood will be returned to the body through a second needle.

Follow-up will continue for 1 year after the last treatment.

Read the detailed description

Background:

  • Recurrent respiratory papillomatosis (RRP) is a rare papillomatous disease of the respiratory tract that is caused by Human Papilloma Virus (HPV) types 6 or 11.
  • RRP can progress to cause severe voice disturbance, airway compromise, fatal pulmonary lesions, and rarely invasive cancers.
  • There is no approved systemic therapy for RRP. Participants require repeated surgical procedures for disease debridement and control.
  • Translational research studies have shown high levels of vascularity in papilloma tissue driven in part by high levels of vascular endothelial growth factor (VEGF)-A mRNA, vascular endothelial growth factor receptors (VEGFR)-1 and VEGFR-2 and elevated serum levels of VEGF-A, particularly in cases of aggressive RRP.
  • Papillomas are also infiltrated by immunosuppressive myeloid and regulatory T-cells.
  • Systemic inhibition of VEGF signaling may reduce VEGF-driven angiogenesis in papillomas and reduce chemotaxis and expansion of immunosuppressive myeloid cells and regulatory T-cells.
  • Bevacizumab is a recombinant humanized monoclonal antibody that binds all active forms of VEGF-A.
  • Bevacizumab is FDA approved for the treatment of metastatic colorectal cancer, non-small cell lung cancer, metastatic renal cell carcinoma, recurrent glioblastoma, cervical cancer, epithelial ovarian cancer, fallopian tube cancer and primary peritoneal cancer and was selected for its demonstrated activity in a variety of cancers and for its acceptable safety profile.
  • Use of systemic bevacizumab in patients with severe and/or tracheal RRP has not been studied prospectively in controlled clinical studies, but clinical safety and activity has been reported in retrospective single institution case series.
  • Bevacizumab resistance can develop in cancer patients due to a variety of tumor escape mechanisms that are unlikely to occur in RRP patients with normal endothelial cells, but bevacizumab re-treatment for recurrent RRP has not been evaluated in controlled clinical studies.

Objective:

-To determine the percentage of participants with an increase in their surgery-free interval during treatment with systemic bevacizumab

Eligibility:

  • Histologically confirmed diagnosis of RRP
  • A history of 2 or more surgeries in the last 12 months in order to control laryngeal and/or tracheal RRP
  • At least one of the following:

    • A Derkay score of 8 or greater
    • Pulmonary RRP with disease measurable by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
    • Tracheal involvement with RRP that has required two or more clinical interventions in the last 12 months
    • Tracheostomy
  • Age >=18 years old
  • Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1

Design:

  • This is a phase II, single arm clinical trial evaluating systemic bevacizumab.
  • Participants will receive bevacizumab (10 mg/kg IV) every three weeks for 3 cycles and then every 6 weeks for a total treatment course of 11 cycles for approximately 1 year total.
  • Operative examination under anesthesia (EUA) with biopsies for research and possible papilloma debulking for safety will be performed before dose 1, optional EUA for research biopsies may be performed following dose 2 and at cycles 6 and 11.
  • Participants may undergo standard-of-care operative EUA with papilloma cleanout during the 1-year treatment period as clinically indicated at the NIH.
  • The mean surgery-free interval during the 1-year treatment period will be compared to the mean surgery-free interval in the 12 months prior to treatment.
  • Participants will also be assessed for papilloma recurrence and surgery-free interval at 6, 12, 24 weeks and every 3 months after that until 1 year following completion of treatment.
  • A total of 20 evaluable participants will be treated on study.
  • During the follow up period, up to 15 participants who develop sufficient papilloma recurrence to require a clinical intervention may be re-treated with 11 additional cycles of bevacizumab (10 mg/kg IV) following the same schedule as the initial treatment.
  • Prior to the initiation of re-treatment, an optional operative EUA with biopsies for research and possible papilloma debulking for safety may be performed.
03

Conditions studied

  • Respiratory Tract Diseases
  • Neoplasms
  • Neoplasms by Histologic Type
  • Neoplasms, Glandular and Epithelial
  • Neoplasms, Squamous Cell
  • Tumor Virus Infections
  • Infections
  • Virus Diseases
  • DNA Virus Infections
  • Pathologic Processes
  • Disease Attributes
  • Recurrence
  • Papilloma
  • Respiratory Tract Infections
  • Papillomavirus Infections

Keywords

  • Human Papilloma Virus
  • Dose Escalation
  • laryngotracheal disease
  • papillomatous disease
04

In context

Respiratory Tract Infections Reclassified

751 studies on the registry are indexed under Respiratory Tract Infections; 114 are open to participants now.

This study's enrollment of 21 is below the median of 200 across 540 interventional studies indexed under Respiratory Tract Infections.

Browse Respiratory Tract Infections studies →

Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,556 studies on the registry; 336 are open to participants now.

Of its 411 completed or terminated interventional studies of FDA-regulated products, 373 (91%) have results posted.

Compared within Respiratory Tract Infections, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Respiratory Tract Diseases. The counts are of registry records indexed under each term, refreshed daily. How we classify →

05

Who can participate

Ages eligible
18 Years to 120 Years
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

  • Age >= 18 years old.
  • confirmed diagnosis of RRP.
  • Individuals must require procedure(s) to remove papillomatous disease per standard of care.(not required for re-treatment)
  • A history of 2 or more surgeries within 12 months prior to treatment initiation in order to control laryngeal and/or tracheal RRP (not required for re-treatment).
  • At least one of the following (not required for re-treatment):

    • A Derkay score of 8 or greater
    • per 1.1 (participants with pulmonary RRP only)
    • Tracheal involvement with RRP that has required two or more clinical interventions in the last 12 months (two or more clinical interventions)
    • Tracheostomy.
  • performance status of 0-1.
  • Individuals must have adequate organ and marrow function as defined below:

    • White blood cells (WBC): >2,000/microL
    • (ANC): >=1,500/microL
    • : >9.0 g/dL
    • : >=100,000/microL
    • Total : \<=1.5 mg/dL, except in participants with Gilbert s Syndrome who must have a total bilirubin less than 3.0 mg/dL
    • (AST) /Alanine aminotransferase (ALT): \<=2.5 X institutional (ULN)
    • Creatinine: within normal institutional limits

OR

(CrCl): >=60 mL/min/1.73 m\^2 for participants with creatinine levels above institutional normal (calculated using the Cockcroft-Gault formula).

  • (PT) /International normalized ratio (INR) and Partial thromboplastin time (PTT): \<=1 X institutional ULN. In participants on anticoagulation, coagulation tests should be within a therapeutic range.
  • Urinalysis: Urine dipstick \< 2+ proteinuria. In participants with >=2+ proteinuria on dipstick urinalysis should undergo a 24-hour urine collection and must demonstrate \<=1g of protein in 24 hours to be eligible

    • Individuals must have received their last systemic therapy for RRP > 4 weeks or 5 half-lives, whichever is longer, prior to treatment initiation, except for systemic bevacizumab which must be > 1 year prior to treatment initiation (not applicable for re-treatment)
    • Individuals able to become pregnant and their partners must agree to use highly effective method of (hormonal, intrauterine device (IUD), surgical sterilization ) for the duration of bevacizumab treatment and up to 6 months after completion of bevacizumab treatment. NOTE: Abstinence, defined as no heterosexual sexual intercourse when this is in line with the preferred and usual lifestyle of the individual is also acceptable.
    • Breastfeeding individuals must be willing to discontinue breastfeeding from study treatment initiation through 6 months after bevacizumab treatment discontinuation.
    • All individuals must have the ability to understand and willingness to sign a written .
    • All individuals must be willing to undergo mandatory during the study (not applicable for re-treatment).

Exclusion criteria

EXCLUSION CRITERIA:

  • History of significant (i.e., active) cardiovascular disease or thromboembolic event: cerebral vascular accident/stroke (within 6 months prior to treatment initiation), myocardial infarction (within 6 months prior to treatment initiation), unstable angina, congestive heart failure (>= Classification Class II), or serious cardiac arrhythmia requiring medication as assessed by .
  • History of abdominal fistula or gastrointestinal perforation within 6 months prior to treatment initiation.
  • Major surgery within 4 weeks prior to treatment initiation.
  • Non-healing wound, active ulcer, or untreated bone fracture.
  • History of hemoptysis (>2.5 mL of bright red blood per episode) within 1 month prior to treatment initiation.
  • Evidence of bleeding diathesis or significant coagulopathy (with or without current therapeutic anticoagulation).
  • Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to treatment initiation.
  • Inadequately controlled hypertension (defined as systolic blood pressure (BP) >150 mmHg and/or diastolic blood pressure > 100 mmHg), an average of 3 BP readings on 2 sessions will be used to measure blood pressure if initial reading indicates inadequately controlled hypertension. NOTE: Anti-hypertensive therapy to achieve blood pressures below these parameters is allowed.
  • Prior history of hypertensive crisis or hypertensive encephalopathy.
  • Persisting toxicity related to prior therapy of Grade >1 per (CTCAE) v 5.0. NOTE: alopecia, sensory neuropathy Grade \<=2 are acceptable.
  • Known active alcohol or drug abuse.
  • History of allergy to study drug components.
  • Pregnancy (confirmed with Beta-Human chorionic gonadotropin (Beta-HCG) serum or urine pregnancy test in performed at screening).
  • Uncontrolled intercurrent illness or situation that would limit compliance with study requirements.
Terms in these criteria, in plain language(19)

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.

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.

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.

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).

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.

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.

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.

Creatinine clearance (CrCl)

How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.

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.

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.

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.

Biopsy and archival tissue

A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.

Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.

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.

ECG (electrocardiogram)

A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.

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.

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.

06

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
21 participants (actual)

Study arms

  • Experimental
    Arm 1

    Bevacizumab treatment course

    Drug: Bevacizumab

Interventions

  • 10 mg/kg IV every three weeks for 3 cycles and then every 6 weeks for a total treatment course of 11 cycles for approximately 1 year total.

07

What researchers measure

Primary outcomes

  1. To determine the percentage of participants with an increase in their surgery-free interval during treatment with systemic bevacizumab.

    Determined by measuring the mean duration between successive clinically indicated surgeries in the 12 months during treatment for that participant and determining whether that duration is longer than the mean duration between successive clinically indicated surgeries in the 12 months prior to treatment by one month or more. This fraction of participants who are classified as having a success will be reported along with a 95% confidence interval.

    Time frame: 1 year

Secondary outcomes

  1. Rate of pulmonary RRP partial response (PR) and complete response (CR) by RECIST 1.1 in participants with pulmonary disease.

    The fraction of participants with a pulmonary RRP partial response and a pulmonary RRP complete response will be reported in all treated pulmonary participants, along with 95% confidence intervals for each.

    Time frame: 6 weeks after completion of treatment

  2. Recurrence free interval after treatment

    Time to recurrence of papillomatous disease after completion of treatment will be recorded and reported descriptively.

    Time frame: Weeks 6, 12, 24 and remote assessment (if needed)

  3. The safety of systemic bevacizumab in participants with aggressive RRP

    Evaluation of safety will be done as follows: each participant will be evaluated for safety and toxicity, and the fraction of participants experiencing AEs will be reported by type and grade of AE

    Time frame: 42 days after the study agent was last administered

  4. The rate of papilloma regrowth by determining the percentage of participants with an increase in their surgery-free interval after treatment with systemic bevacizumab

    The rate of papilloma regrowth will be determined by measuring the mean duration between successive clinically indicated surgeries in the 12 months after treatment for that participant and determining whether that duration is longer than the mean duration between successive clinically indicated surgeries in the 12 months prior to treatment by one month or more. This fraction of participants who are classified as having a success will be reported along with a 95% confidence interval.

    Time frame: Weeks 6, 12, 24 after completion of treatment, every 3 months after that with the last evaluation performed at 1 year after completion of study treatment

08

Study locations

1 site
  • National Institutes of Health Clinical Center
    Bethesda, Maryland 20892, United States
09

References and documents

Individual participant data

Plan to share: Yes — All collected IPD will be shared.

Supporting information: Study protocol, Statistical analysis plan, Informed consent form

Time frame: Clinical data available during the study and indefinitely.

Access criteria: Data from this study may be requested by contacting the PI.

10

Timeline

2 registry updates since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Started Aug 2023 (actual). Primary completion is estimated for Jul 2027, 47 months after the start.

Of 32 phase 2 interventional studies under Respiratory Tract Infections, half reached primary completion within 11 months of starting (the median), counting those still running; a quarter within 8 and three quarters within 25. This study's planned 47 months is above that.

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

Registered
Apr 1, 2023
First posted
Apr 4, 2023
StartActual
Aug 2, 2023
Primary completionEst.
Jul 31, 2027
CompletionEst.
Jan 1, 2029
Last update
Nov 3, 2026
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.
Minor edits
Nothing that changes what the study is or who can join. Edited: description
2 updates, last Nov 3, 2026
Show all 2 updates
  1. Nov 3, 2026
    Minor edits only
    + 1 other change: description
  2. Oct 29, 2026
    Minor edits only
    + 1 other change: description

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

11

Registry details

Key details

Study ID
NCT05797246
Responsible party
Sponsor
First posted
Apr 4, 2023
Start date
Aug 2, 2023
Primary completion
Jul 31, 2027 (estimated)
Completion
Jan 1, 2029 (estimated)
Last update
Nov 3, 2026

Study contacts

Scott M Norberg, D.O.
principal investigator · National Cancer Institute (NCI)

Oversight

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

Not currently enrolling

This study is active, not recruiting, as verified in Jan 2026. You cannot join it, but the record below documents what was studied.

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Studies of the drug tested here: Bevacizumab

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