- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02135419
Treatment in Preventing Anal Cancer in Patients With HIV and Anal High-Grade Lesions (ANCHOR)
ANCHOR Study: Anal Cancer/HSIL Outcomes Research Study
The randomized phase of the trial compared topical or ablative treatment with active monitoring in preventing anal cancer in patients with human immunodeficiency virus (HIV) and high-grade squamous intraepithelial lesions (HSIL). Anal HSIL is tissue in the anal canal that has been damaged by infection with human papillomavirus (HPV) and is at risk for turning into anal cancer.
The ANCHOR Data Safety Monitoring Board (DSMB) determined that the primary study endpoint was completed, based on the data and statistical analysis presented to them on 07SEP2021.
In the post-randomization phase of this trial, all enrolled participants are offered treatment for HSIL and/or follow-up, at the participant's choice.
Study Overview
Status
Conditions
Detailed Description
PRIMARY OBJECTIVES: The primary objective of this study has been completed for efficacy.
I. To determine the effectiveness of treating anal HSIL to reduce the incidence of anal cancer in human immunodeficiency virus (HIV)-infected men and women.
SECONDARY OBJECTIVES:
I. To determine the safety of infrared coagulation (IRC), electrocautery, imiquimod, laser and 5- fluorouracil treatments for anal HSIL.
II. To assess the responsiveness (sensitivity to change) and clinical significance of the ANCHOR Health-Related Symptom Index (A-HRSI) subscales by comparing change scores within groups of participants as defined by participant responses to the participant global impression of change (PGIC) item. (completed FEB2020)
TERTIARY OBJECTIVES:
Collect clinical specimens and data to create a bank of well-annotated specimens that will enable correlative science:
I. Identification of viral factors in HSIL progression to cancer; II. Identification of host factors in HSIL progression to cancer; III. Identify host and viral biomarkers of progression from HSIL to cancer; IV. Identify medical history and behavioral risk factors for HSIL progression to cancer.
QUALITY OF LIFE OBJECTIVES (completed FEB2022) I. Primary QOL Objective: To compare arms in terms of changes in physical symptoms and impacts from T2 to T3, adjusting for T1.
ANCILLARY (COVID SUPPLEMENT) SUBSTUDY OBJECTIVES:
I. Determine the prevalence of SARS-CoV-2 detection in anal and oropharyngeal swabs among people living with HIV (PLWH) being screened for and enrolled in the ANCHOR study.
II. Determine the relationship between prevalent anal SARS-CoV-2 positivity, anal HPV infection, and anal high-grade squamous intraepithelial lesions (HSIL).
III. Determine the 6-month incidence of SARS-CoV-2 detection in anal and oropharyngeal swabs among participants in the active monitoring arm being assessed for the first time for treatment and individuals already enrolled in the COVID substudy under protocol version 15.0.
IV. Determine the relationship between prevalent or incident SARS-CoV-2 detection and regression of anal HPV infection or HSIL among active monitoring arm participants already enrolled in the COVID substudy under protocol version 15.0, and those who continue the protocol and who choose not to be treated at visit 101.
OUTLINE: The randomized strategy to study the efficacy of HSIL treatment to reduce the risk of progression to anal cancer, as compared to active monitoring, was discontinued for all participants.
Patients are randomized to 1 of 2 treatment arms. (accrual closed SEP2021)
ARM I: Patients are directed to receive either topical or ablative treatment at the discretion of the clinician. Patients receiving topical treatment apply topical imiquimod intra-anally, peri-anally or both thrice weekly for up to 16 weeks, or topical 5-fluorouracil twice daily for 5 days every 2 weeks for up to 16 weeks. Patients receiving ablative treatment using infrared coagulation, hyfrecation/electrocautery, or laser. Patients may undergo excision under anesthesia if the clinician believes none of the other treatment approaches will be effective. The number and timing of such treatments will be at the discretion of the investigator. Patients with persistent HSIL should continue a protocol-approved treatment or a new protocol treatment should be considered.
ARM II: Patients undergo active monitoring with HRA examinations and anal cytology every 6 months. Every 12 months, patients undergo biopsies of visible lesions.
Participants on both arms are to be followed for up to 5 years after randomization of the last participant.
Post-randomization phase: Individuals in the treatment arm may continue treatment, and participants in the active monitoring arm are offered treatment. If upon assessment participants continue to have HSIL but do not intend to get treatment, they will be monitored for the potential for disease progression to anal cancer.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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San Juan, Puerto Rico, 00936
- University of Puerto Rico
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California
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Los Angeles, California, United States, 90095
- UCLA School of Nursing
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Los Angeles, California, United States, 90035
- UCLA CARE Clinic
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Palm Springs, California, United States, 92262
- DAP Health
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San Francisco, California, United States, 94115
- University of California at San Francisco Anal Dysplasia Clinic
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Colorado
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Aurora, Colorado, United States, 80045
- University of Colorado Hospital
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Denver, Colorado, United States, 80204
- Denver public Health
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District of Columbia
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Washington, District of Columbia, United States, 20009
- Dupont Circle Physicians Group
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Washington, District of Columbia, United States, 20006
- Capital Digestive Care
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Florida
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Miami, Florida, United States, 33136
- ACC Clinic, Jackson Hospital
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Miami, Florida, United States, 33136
- University of Miami Miller School of Medicine - Sylvester Cancer Center
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Georgia
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Atlanta, Georgia, United States, 30303
- Grady Health System
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Illinois
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Chicago, Illinois, United States, 60614
- Anal Dysplasia Clinic MidWest
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Louisiana
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New Orleans, Louisiana, United States, 70112
- University Medical Center New Orleans
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New Orleans, Louisiana, United States, 70119
- CrescentCare Health
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Massachusetts
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Boston, Massachusetts, United States, 02118
- Boston Medical Center
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Boston, Massachusetts, United States, 02215
- Fenway Health
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New Jersey
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Newark, New Jersey, United States, 07103
- Rutgers University New Jersey Medical School
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New York
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Bronx, New York, United States, 10461
- Montefiore - Albert Einstein College of Medicine
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New York, New York, United States, 10011
- Laser Surgery Care
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New York, New York, United States, 10010
- Cornell Clinical Trials Unit, Chelsea Center
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North Carolina
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Winston-Salem, North Carolina, United States, 27157
- Wake Forest Baptist Health
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Washington
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Seattle, Washington, United States, 98104
- Harborview Medical Center
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Seattle, Washington, United States, 98101
- Virginia Mason Medical Center
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Seattle, Washington, United States, 98104
- The Polyclinic
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- HIV positive. Documentation of HIV-1 infection by means of any one of the following: 1) Documentation of HIV diagnosis in the medical record by a licensed health care provider; 2) Documentation of receipt of ART by a licensed health care provider (receipt of at least two agents is required); 3) HIV-1 RNA detection by a licensed HIV-1 RNA assay demonstrating >1000 RNA copies/mL; or, 4) Any licensed HIV screening antibody and/or HIV antibody/antigen combination assay confirmed by a second licensed HIV assay such as a HIV-1 Western blot confirmation or HIV rapid multispot antibody differentiation assay.
- Biopsy-proven HSIL at baseline
- At least one focus of HSIL must be identified that is not within a condyloma that may be treated after enrollment into the study
- For females, documentation that the participant is being followed for cervical cytology (if having a cervix) and/or HPV testing per current ASCCP guidelines, and visual examination of the vulva, vagina, and cervix to rule out cancer/suspicion for cancer within 12 months prior to enrollment
- Eastern Cooperative Oncology Group (ECOG) performance status <= 1 (Karnofsky >= 70%)
- Life expectancy of greater than 5 years
- Absolute neutrophil count: >= 750/mm^3
- Platelets: >= 75,000/mm^3
- Hemoglobin >= 9.0 g/dL
- Women of childbearing potential must have a negative urine pregnancy test within 7 days of initiating study treatment if they have been randomized to the treatment arm; all women of childbearing potential must agree to use a reliable birth control method (oral contraceptive pills, intrauterine device, Nexplanon, DepoProvera, or permanent sterilization, etc., or another acceptable method as determined by the investigator) during the entire period of the trial (5 years or more), and must not intend to become pregnant during study participation and for 3 months after treatment is discontinued; all participants must be willing to comply with an acceptable birth control regimen as determined by the Investigator
- Men randomized to the treatment arm should not father a baby while receiving topical treatment during this study. Men who could father a child must agree to use at least one form of birth control during or continued abstinence from heterosexual intercourse if receiving topical treatment during the study, and for 2 weeks after stopping topical treatment.
- Ability to understand and the willingness to sign a written informed consent document
- Participant is willing to be randomized and able to comply with the protocol
- Clinician is comfortable with either following patient for up to 5 years without therapy or treating patient for up to 5 years
Exclusion Criteria:
- Inability to provide informed consent
- Patients who are receiving any other immunomodulatory investigational agents (replacement doses of steroids for adrenal insufficiency or treatment with prednisone ≤5 mg/day is permitted) within the 4 weeks before randomization enrollment, other than investigational antiretroviral agents for HIV, or investigational or approved agents for Hepatitis C.
- History of anal cancer, penile, vulvar, vaginal or cervical cancer, or signs of these cancers at baseline.
- Treatment or removal of HSIL less than 6 months prior to randomization.
- Participant has symptoms related to HSIL and would benefit more from immediate treatment than from entry into the study and potential for randomization to active monitoring arm
- Current systemic chemotherapy or radiation therapy that potentially causes bone marrow suppression that would preclude safe treatment of HSIL
- Participants who only have a single HSIL lesion that is likely to be removed entirely with the initial screening biopsy
- Warts so extensive that they preclude the clinician from determining the extent and location of HSIL
- Participant plans to relocate away from the study site to a location without an ANCHOR study site during study participation
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Arm I (treatment)
Patients are directed to receive either topical or ablative treatment at the discretion of the clinician.
Patients receiving topical treatment apply imiquimod intra-anally, peri-anally or both thrice weekly for up to 16 weeks, fluorouracil twice daily for 5 days every 2 weeks for up to 16 weeks, or trichloroacetic acid every 3 weeks up to 12 weeks.
Patients receiving ablative treatment using infrared photocoagulation therapy, hyfrecation/electrocautery (thermal ablation therapy), or laser therapy.
Patients may undergo excision under anesthesia if the clinician believes none of the other treatment approaches will be effective.
The number and timing of such treatments will be at the discretion of the investigator.
Patients with persistent HSIL should continue a protocol-approved treatment or a new protocol treatment should be considered.
All participants will have samples collected for laboratory biomarker analysis.
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Correlative studies
Applied topically
Other Names:
Applied topically
Other Names:
Undergo infrared coagulation
Other Names:
Undergo hyfrecation/electrocautery therapy
Undergo laser therapy
Other Names:
Undergo active monitoring (High Resolution Anoscopy [HRA]) with biopsies
Other Names:
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Active Comparator: Arm II (active monitoring) (closed since SEP2021)
Patients undergo active monitoring with examinations for clinical observation every 6 months.
Every 12 months, patients undergo biopsies of visible lesions.
Patients have cytology sampling performed at every visit.
All participants will have samples collected for laboratory biomarker analysis.
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Correlative studies
Undergo active monitoring (High Resolution Anoscopy [HRA]) with biopsies
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Anal Cancer Incidence
Time Frame: Time from randomization to diagnosis of anal cancer, assessed up to 5 years post randomization
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Anal cancer incidence is calculated as the number of anal cancer cases detected per 100,000 person years
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Time from randomization to diagnosis of anal cancer, assessed up to 5 years post randomization
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of Adverse Events for Each Treatment
Time Frame: Up to 5 years after randomization
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Participants who had at least one adverse event (serious or non-serious)
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Up to 5 years after randomization
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Change in Physical Symptom Score From Baseline (2-7 Days Post Randomization) Until 4 Weeks Post Randomization
Time Frame: 4 weeks post randomization
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The physical symptom score is made up of the sum of responses to whether or not the participant had any of the 9 physical symptoms: anal pain, pain other than anal pain, pain during bowel movements, constipation, bleeding from anus, itching in/around the anus, discharge (wetness) in anal area, burning sensations in the anal area, and urgency for bowel movements.
Responses are 0- not at all, 1-a little bit, 2-somewhat, 3-quite a bit, 4-very much.
Thus physical symptom score ranges from 0 to 36.
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4 weeks post randomization
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Viral Factors in HSIL Progression to Cancer
Time Frame: Up to 5 years after randomization
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Descriptive statistics will be used to describe the integration locus of HPV In the invasive cancers and whether they differ from those of the overlying HSIL.
Descriptive statistics will also be used to determine if the loci differ in HSIL that have progressed and concurrent HSIL biopsies that did not progress.
In each case only tissues that contain HPV 16 will be analyzed.
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Up to 5 years after randomization
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Host Factors in HSIL Progression to Cancer
Time Frame: Up to 5 years after randomization
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Linear models will be fitted for each gene.
Moderated t-statistics, fold-change and the associated p values will be calculated for each gene.
Since thousands of genes will be tested, false discovery rate (FDR)-adjusted values will be calculated using the Benjamini-Hochberg method.
FDR values indicate the expected fraction of falsely declared differentially expressed (DE) genes among the total set of declared DE genes, i.e.
FDR = 0.15 would indicate that 15% of the declared DE genes were expected to be false due to experimental noise instead of actual differential expression.
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Up to 5 years after randomization
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Host and Viral Biomarkers of Progression From HSIL to Cancer
Time Frame: Up to 5 years after randomization
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Biomarkers that are correlated with progression from anal HSIL to anal cancer
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Up to 5 years after randomization
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Behavioral Risk Factors for HSIL Progression to Cancer
Time Frame: Up to 5 years after randomization
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For each risk factor of interest, Fisher's exact test or Pearson's chi-square test will be used to determine if there is an association.
Factors associated with invasive anal cancer at the 0.10 significance level will be incorporated into a logistic regression model to determine if they are independently associated with invasive anal cancer.
Cox regression analyses will also be used to evaluate the association between risk factors and time to diagnosis of invasive anal cancer.
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Up to 5 years after randomization
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ANCHOR Study Health-Related Symptom Index (A-HRSI) Scale Responsiveness (Sensitivity to Change)
Time Frame: A-HRSI and self-reported Patient Global Impression of Change (PGIC) scale and ECOG Performance Status (ECOG PS) item were administered at time of enrollment (T1) up until time of trial randomization (T2), and 71-112 days post-randomization (T3).
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Participants at follow-up timepoints were categorized into two sets of three groups based on PGIC and ECOG PS responses ("worse," "no change," "better"), with the primary responsiveness analysis using these three groups in a one-way analysis of variance (ANOVA).
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A-HRSI and self-reported Patient Global Impression of Change (PGIC) scale and ECOG Performance Status (ECOG PS) item were administered at time of enrollment (T1) up until time of trial randomization (T2), and 71-112 days post-randomization (T3).
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Quality of Life Assessment Measured by the A-HRSI (Validated Tool)
Time Frame: A-HRSI completion occurred at 3 time points: Pre-randomization (T1), within 2-7 days (T2) and at 4 weeks of treatment/randomization (T3).
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A-HRSI physical symptoms and physical impacts subscale change scores (T3 minus T2) using an analysis of covariance adjusting for the covariate baseline (T1) subscale to test for differences between arms at a one-sided 0.025 significance level with approximately 90% power.
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A-HRSI completion occurred at 3 time points: Pre-randomization (T1), within 2-7 days (T2) and at 4 weeks of treatment/randomization (T3).
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Joel Palefsky, MD, AIDS Malignancy Consortium
Publications and helpful links
General Publications
- Lee JY, Lensing SY, Berry-Lawhorn JM, Jay N, Darragh TM, Goldstone SE, Wilkin TJ, Stier EA, Einstein M, Pugliese JC, Palefsky JM; ANCHOR Investigators. Design of the ANal Cancer/HSIL Outcomes Research study (ANCHOR study): A randomized study to prevent anal cancer among persons living with HIV. Contemp Clin Trials. 2022 Feb;113:106679. doi: 10.1016/j.cct.2022.106679. Epub 2022 Jan 10.
- Palefsky JM, Lee JY, Jay N, Goldstone SE, Darragh TM, Dunlevy HA, Rosa-Cunha I, Arons A, Pugliese JC, Vena D, Sparano JA, Wilkin TJ, Bucher G, Stier EA, Tirado Gomez M, Flowers L, Barroso LF, Mitsuyasu RT, Lensing SY, Logan J, Aboulafia DM, Schouten JT, de la Ossa J, Levine R, Korman JD, Hagensee M, Atkinson TM, Einstein MH, Cracchiolo BM, Wiley D, Ellsworth GB, Brickman C, Berry-Lawhorn JM; ANCHOR Investigators Group. Treatment of Anal High-Grade Squamous Intraepithelial Lesions to Prevent Anal Cancer. N Engl J Med. 2022 Jun 16;386(24):2273-2282. doi: 10.1056/NEJMoa2201048.
- Barroso LF, Stier EA, Hillman R, Palefsky J. Anal Cancer Screening and Prevention: Summary of Evidence Reviewed for the 2021 Centers for Disease Control and Prevention Sexually Transmitted Infection Guidelines. Clin Infect Dis. 2022 Apr 13;74(Suppl_2):S179-S192. doi: 10.1093/cid/ciac044.
- Higashi RT, Rodriguez SA, Betts AC, Tiro JA, Luque AE, Rivera R, Barnes A. Anal cancer screening among women with HIV: provider experiences and system-level challenges. AIDS Care. 2022 Feb;34(2):220-226. doi: 10.1080/09540121.2021.1883512. Epub 2021 Feb 17.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- Virus Diseases
- Sexually Transmitted Diseases, Viral
- Sexually Transmitted Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Uterine Cervical Diseases
- Uterine Diseases
- Disease Attributes
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Intestinal Diseases
- DNA Virus Infections
- Intestinal Neoplasms
- Rectal Diseases
- Tumor Virus Infections
- Colorectal Neoplasms
- Precancerous Conditions
- Neoplasms, Squamous Cell
- Rectal Neoplasms
- Anus Diseases
- Uterine Cervical Dysplasia
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Genital Diseases
- Genital Diseases, Female
- Carcinoma in Situ
- Infections
- Communicable Diseases
- Carcinoma, Squamous Cell
- Anus Neoplasms
- Papillomavirus Infections
- Papilloma
- Squamous Intraepithelial Lesions of the Cervix
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Adjuvants, Immunologic
- Interferon Inducers
- Fluorouracil
- Imiquimod
Other Study ID Numbers
- AMC-A01 (Other Identifier: CTEP)
- UM1CA121947 (U.S. NIH Grant/Contract)
- U01CA121947 (U.S. NIH Grant/Contract)
- NCI-2014-00636 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- ANCHOR (Other Identifier: AIDS Malignancy Consortium)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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.
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