- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00002593
S9415 Chemotherapy in Patients With Stage II or III Colon Cancer That Has Been Surgically Removed
Phase III Randomized Trial of 5-FU/Leucovorin/Levamisole Versus 5-FU Continuous Infusion/Levamisole as Adjuvant Therapy for High-Risk Resectable Colon Cancer
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving drugs in different ways may kill more cancer cells.
PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy given in different ways in treating patients with surgically removed stage II or stage III colon cancer at high risk of recurrence.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
OBJECTIVES: I. Compare overall and disease free survival in patients with completely resected stage II or III colon cancer randomized to adjuvant chemotherapy with bolus fluorouracil and leucovorin calcium with levamisole vs continuous infusion fluorouracil with levamisole.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to center, T stage (T1 vs T2 vs T3 vs T4a), N stage (N0 vs N1 vs N2-3), and time from surgery until registration (21-28 vs 29-35 days). Patients are randomized to one of two treatment arms. Arm I: Patients receive leucovorin calcium IV immediately followed by fluorouracil IV on days 1 through 5 of weeks 1, 5, 9, 14, 19, and 24, and oral levamisole 3 times a day for 3 days on days 1-3. Courses repeat every 2 weeks for 6 months. Arm II: Patients receive levamisole as in arm I plus fluorouracil by continuous IV infusion for 8 weeks. Treatment with fluorouracil repeats every 10 weeks for 3 courses. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed at 9 months and 12 months, then every 6 months for 4 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 1,500 patients will be accrued for the study over approximately 5.5 years.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Saskatchewan
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Regina, Saskatchewan, Canada, S4S 6X3
- Saskatchewan Cancer Agency
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San Juan, Puerto Rico, 00927-5800
- Veterans Affairs Medical Center - San Juan
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Pretoria, South Africa, 0001
- Pretoria Academic Hospital
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Arizona
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Scottsdale, Arizona, United States, 85259-5404
- CCOP - Scottsdale Oncology Program
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California
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Palo Alto, California, United States, 94304
- Veterans Affairs Medical Center - Palo Alto
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San Francisco, California, United States, 94115-0128
- UCSF Cancer Center and Cancer Research Institute
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Stanford, California, United States, 94305-5408
- Stanford University Medical Center
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Colorado
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Denver, Colorado, United States, 80209-5031
- CCOP - Colorado Cancer Research Program, Inc.
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District of Columbia
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Washington, District of Columbia, United States, 20307-5000
- Walter Reed Army Medical Center
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Florida
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Miami, Florida, United States, 33136
- Sylvester Cancer Center, University of Miami
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Georgia
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Atlanta, Georgia, United States, 30322
- Emory University Hospital - Atlanta
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Decatur, Georgia, United States, 30033
- Veterans Affairs Medical Center - Atlanta (Decatur)
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Illinois
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Chicago, Illinois, United States, 60637
- University of Chicago Cancer Research Center
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Chicago, Illinois, United States, 60611
- Robert H. Lurie Comprehensive Cancer Center, Northwestern University
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Chicago, Illinois, United States, 60611
- Veterans Affairs Medical Center - Chicago (Lakeside)
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Peoria, Illinois, United States, 61602
- CCOP - Illinois Oncology Research Association
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Urbana, Illinois, United States, 61801
- CCOP - Carle Cancer Center
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Iowa
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Cedar Rapids, Iowa, United States, 52403-1206
- CCOP - Cedar Rapids Oncology Project
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Des Moines, Iowa, United States, 10309-1016
- CCOP - Iowa Oncology Research Association
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Sioux City, Iowa, United States, 51101-1733
- Siouxland Hematology-Oncology
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Louisiana
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New Orleans, Louisiana, United States, 70121
- CCOP - Ochsner
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Massachusetts
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Boston, Massachusetts, United States, 02215
- Beth Israel Deaconess Medical Center
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Boston, Massachusetts, United States, 02115
- Dana-Farber Cancer Institute
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Worcester, Massachusetts, United States, 01655
- University of Massachusetts Memorial Medical Center
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Michigan
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Kalamazoo, Michigan, United States, 49007-3731
- CCOP - Kalamazoo
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Minnesota
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Duluth, Minnesota, United States, 55805
- CCOP - Duluth
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Minneapolis, Minnesota, United States, 55455
- University of Minnesota Cancer Center
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Rochester, Minnesota, United States, 55905
- Mayo Clinic Cancer Center
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Saint Cloud, Minnesota, United States, 56303
- CentraCare Clinic
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Saint Louis Park, Minnesota, United States, 55416
- CCOP - Metro-Minnesota
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Missouri
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Saint Louis, Missouri, United States, 63110
- Barnes-Jewish Hospital
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Nebraska
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Omaha, Nebraska, United States, 68131
- CCOP - Missouri Valley Cancer Consortium
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Nevada
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Las Vegas, Nevada, United States, 89106
- CCOP - Southern Nevada Cancer Research Foundation
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New York
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Albany, New York, United States, 12208
- Veterans Affairs Medical Center - Albany
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Bronx, New York, United States, 10461
- Albert Einstein Comprehensive Cancer Center
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Buffalo, New York, United States, 14263-0001
- Roswell Park Cancer Institute
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Manhasset, New York, United States, 11030
- North Shore University Hospital
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New York, New York, United States, 10029
- Mount Sinai Medical Center, NY
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Rochester, New York, United States, 14642
- University of Rochester Cancer Center
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Syracuse, New York, United States, 13210
- State University of New York - Upstate Medical University
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North Carolina
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Chapel Hill, North Carolina, United States, 27599-7295
- Lineberger Comprehensive Cancer Center, UNC
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Winston-Salem, North Carolina, United States, 27104-4241
- CCOP - Southeast Cancer Control Consortium
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Winston-Salem, North Carolina, United States, 27157-1082
- Comprehensive Cancer Center of Wake Forest University Baptist Medical Center
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North Dakota
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Bismarck, North Dakota, United States, 58501
- Quain & Ramstad Clinic, P.C.
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Grand Forks, North Dakota, United States, 58201
- Altru Health Systems
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Ohio
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Cleveland, Ohio, United States, 44106-5065
- Ireland Cancer Center
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Toledo, Ohio, United States, 43623-3456
- CCOP - Toledo Community Hospital Oncology Program
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Pennsylvania
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Danville, Pennsylvania, United States, 17822-2001
- CCOP - Geisinger Clinical and Medical Center
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Philadelphia, Pennsylvania, United States, 19111
- Fox Chase Cancer Center
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Pittsburgh, Pennsylvania, United States, 15213
- University of Pittsburgh Cancer Institute
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Rhode Island
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Providence, Rhode Island, United States, 02903
- Rhode Island Hospital
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South Dakota
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Rapid City, South Dakota, United States, 57709
- Rapid City Regional Hospital
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Sioux Falls, South Dakota, United States, 57105-1080
- CCOP - Sioux Community Cancer Consortium
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Tennessee
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Memphis, Tennessee, United States, 38163
- University of Tennessee, Memphis Cancer Center
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Vermont
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Burlington, Vermont, United States, 05401-3498
- Vermont Cancer Center
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Wisconsin
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Madison, Wisconsin, United States, 53705
- Veterans Affairs Medical Center - Madison
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Madison, Wisconsin, United States, 53792
- University of Wisconsin Comprehensive Cancer Center
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Marshfield, Wisconsin, United States, 54449
- CCOP - Marshfield Medical Research and Education Foundation
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Milwaukee, Wisconsin, United States, 53226
- Medical College Of Wisconsin
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Milwaukee, Wisconsin, United States, 53295
- Veterans Affairs Medical Center - Milwaukee (Zablocki)
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
DISEASE CHARACTERISTICS: Histologically proven resectable stage II or III adenocarcinoma of the colon Caudal margin of the primary tumor must lie above the peritoneal reflection Must have pathologic confirmation of either N1-3 (stage III), or if N0, must have T3-T4 (stage II) with bowel obstruction or perforation Obstruction documented as: At least 75% colon or small bowel obstruction on x-ray and/or endoscopy Significant bowel dilatation surgically documented Significant obstruction described in the pathology report Perforation documented by gross operative/pathologic evidence of a colon wall defect with associated abscess or peritonitis Complete en bloc resection by laparotomy required No laparoscopic colectomy without prior surgery on protocol SWOG-9411 No gross or microscopic residual disease No distant peritoneal metastases (stage IV) even if grossly resectable No requirement to open the pelvic peritoneum to define the extent of disease No extrapelvic nodal metastasis unless resected en bloc with the primary tumor No distant metastases No other diagnosis of stage II-III colon cancer within the past 5 years May have undergone complete surgical resection at least 5 years prior to study Completely resected prior or synchronous stage 0-I colon cancer eligible
PATIENT CHARACTERISTICS: Age: Adult Performance status: SWOG 0-2 Hematopoietic: WBC (white blood cell) at least 3,500/mm3 Platelet count at least within the lower limit of normal Hepatic: Bilirubin no greater than 2 times upper limit of normal (ULN) AST (angiotensin sensitivity test) no greater than 2 times ULN Alkaline phosphatase no greater than 2 times ULN Renal: Creatinine no greater than 2 times ULN Other: No organic brain syndrome, Alzheimer's disease, or other altered mental status No second malignancy within 5 years except: Adequately treated nonmelanomatous skin cancer Adequately treated carcinoma in situ of the cervix Not pregnant or nursing Negative pregnancy test Effective contraception required of fertile patients
PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior fluorouracil or other chemotherapy for cancer No concurrent chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior or concurrent radiotherapy for cancer Surgery: Complete en bloc resection required (see Disease Characteristics)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: 5-FU/Leucovorin/Levamisole
levamisole hydrochloride: 50 mg every 8 hours x 3 days, PO, repeat every 14 days for 6 months; leucovorin calcium: 20 mg/m^2/day, IV, Days 1-5 of each cycle; 5-fluorouracil: 425 mg/m^2/day, IV, Days 1-5 of each cycle;
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Given IV as described in Arm Description
Other Names:
Given IV as described in Arm description.
Other Names:
Given as described in arm description
Other Names:
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Active Comparator: Infusional 5-FU + Levamisole
levamisole hydrochloride : 50 mg every 8 hours x 3 days, PO, repeat every 14 days for 6 months; 5-fluorouracil: 250 mg/m^2/day, continuous infusion, daily for 56 days x 3 cycles of 8 weeks.
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Given IV as described in Arm Description
Other Names:
Given as described in arm description
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Compare effectiveness of bolus 5-FU, leucovorin, levamisole vs continuous infusion 5-FU, levamisole as adjuvant therapy for patients with colon cancer, measured in overall survival
Time Frame: At death
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At death
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
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Disease free survival
Time Frame: Until progression
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Until progression
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Chair: Elizabeth A. Poplin, MD, Rutgers Cancer Institute of New Jersey
- Study Chair: Robert J. Mayer, MD, FACP, Dana-Farber Cancer Institute
- Study Chair: Daniel G. Haller, MD, Abramson Cancer Center of the University of Pennsylvania
- Study Chair: Richard M. Goldberg, MD, Mayo Clinic
Publications and helpful links
General Publications
- Yothers G, Sargent DJ, Wolmark N, Goldberg RM, O'Connell MJ, Benedetti JK, Saltz LB, Dignam JJ, Blackstock AW; ACCENT Collaborative Group. Outcomes among black patients with stage II and III colon cancer receiving chemotherapy: an analysis of ACCENT adjuvant trials. J Natl Cancer Inst. 2011 Oct 19;103(20):1498-506. doi: 10.1093/jnci/djr310. Epub 2011 Oct 12.
- Poplin EA, Benedetti JK, Estes NC, Haller DG, Mayer RJ, Goldberg RM, Weiss GR, Rivkin SE, Macdonald JS. Phase III Southwest Oncology Group 9415/Intergroup 0153 randomized trial of fluorouracil, leucovorin, and levamisole versus fluorouracil continuous infusion and levamisole for adjuvant treatment of stage III and high-risk stage II colon cancer. J Clin Oncol. 2005 Mar 20;23(9):1819-25. doi: 10.1200/JCO.2005.04.169.
- Poplin E, Benedetti J, Estes N, et al.: Phase III randomized trial of bolus 5-FU/leucovorin/levamisole versus 5-FU continuous infusion/levamisole as adjuvant therapy for high risk colon cancer (SWOG 9415/INT-0153). [Abstract] Proceedings of the American Society of Clinical Oncology 19: A931, 2000.
- Leichman CG, Poplin E, Zalupski M, et al.: A pilot trial of infusion 5-fluorouracil with levamisole as adjuvant therapy for stage III colon cancer. [Abstract] Proceedings of the American Society of Clinical Oncology 14: A-460, 196, 1995.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms
- Neoplasms by Site
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Colonic Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Colorectal Neoplasms
- Colonic Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Protective Agents
- Micronutrients
- Adjuvants, Immunologic
- Vitamins
- Calcium-Regulating Hormones and Agents
- Antiparasitic Agents
- Antidotes
- Vitamin B Complex
- Antinematodal Agents
- Anthelmintics
- Fluorouracil
- Leucovorin
- Calcium
- Levoleucovorin
- Levamisole
Other Study ID Numbers
- CDR0000063773
- U10CA032102 (U.S. NIH Grant/Contract)
- SWOG-9415 (Other Identifier: SWOG)
- CLB-9498 (Other Identifier: CALGB)
- INT-0153 (Other Identifier: NCI)
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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