Evaluation of Carboplatin/Paclitaxel With and Without Trastuzumab (Herceptin) in Uterine Serous Cancer

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ClinicalTrials.gov Identifier: NCT01367002

Recruitment Status : Completed

First Posted : June 6, 2011

Results First Posted : April 18, 2023

Last Update Posted : May 17, 2023

View this study on Beta.ClinicalTrials.gov

Sponsor:

Collaborator:

Genentech, Inc.

Information provided by (Responsible Party):

Yale University

Study Description

Brief Summary:

The primary objective of this study is to estimate whether the addition of trastuzumab to paclitaxel and carboplatin chemotherapy improves progression free survival when compared to paclitaxel and carboplatin alone in Uterine Serous Papillary Carcinoma (USPC) patients overexpressing Her2/neu at 3+ level by immunohistochemistry (IHC)or positive by fluorescence in situ hybridization (FISH).

Condition or disease	Intervention/treatment	Phase
Endometrial Cancer	Drug: Carboplatin/Paclitaxel Drug: Trastuzumab	Phase 2

Detailed Description:

The purpose of this study is to perform a randomized Phase II evaluation of Carboplatin/Paclitaxel with or without Trastuzumab (Herceptin) in patients with HER2/neu+ advanced stage/recurrent disease with an emphasis on determining the progression free survival in USPC patients and assessing immunologic markers predictive of trastuzumab response.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	61 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Randomized Phase II Evaluation of Carboplatin/Paclitaxel With and Without Trastuzumab (Herceptin) in HER2/Neu+ Patients With Advance/Recurrent Uterine Serous Papillary Carcinoma
Study Start Date :	June 2011
Actual Primary Completion Date :	June 30, 2022
Actual Study Completion Date :	June 30, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Paclitaxel Carboplatin Trastuzumab

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Carboplatin/Paclitaxel Chemotherapy	Drug: Carboplatin/Paclitaxel Paclitaxel 175 mg/m2 will administered intravenously every 21 days for 6 cycles. Carboplatin AUC 5 will be administered intravenously every 21 days for 6 cycles. 100% of patients will receive Carboplatin/Paclitaxel. Other Names: Taxus brevifolia cis-Diammine
Experimental: Trastuzumab Monoclonal antibody	Drug: Trastuzumab Paclitaxel 175 mg/m2 will be administered intravenously every 21 days for 6 cycles. Carboplatin AUC 5 will be administered intravenously every 21 days for 6 cycles. On day 1, an 8 mg/kg loading dose of trastuzumab will be administered over a 90 minute period. Beginning on day 21, patients will receive 6mg/kg of trastuzumab, administered intravenously every 21 days and continued indefinitely every 21 days after 6 cycles of cytotoxic therapy are completed and until progression of the disease or prohibitive toxicities occur. 50% of patients will receive Carboplatin/Paclitaxel with the addition of Trastuzumab. Other Name: Herceptin

Arm

Intervention/treatment

Active Comparator: Carboplatin/Paclitaxel

Chemotherapy

Drug: Carboplatin/Paclitaxel

Paclitaxel 175 mg/m2 will administered intravenously every 21 days for 6 cycles. Carboplatin AUC 5 will be administered intravenously every 21 days for 6 cycles. 100% of patients will receive Carboplatin/Paclitaxel.

Other Names:

Taxus brevifolia
cis-Diammine

Experimental: Trastuzumab

Monoclonal antibody

Drug: Trastuzumab

Paclitaxel 175 mg/m2 will be administered intravenously every 21 days for 6 cycles. Carboplatin AUC 5 will be administered intravenously every 21 days for 6 cycles. On day 1, an 8 mg/kg loading dose of trastuzumab will be administered over a 90 minute period. Beginning on day 21, patients will receive 6mg/kg of trastuzumab, administered intravenously every 21 days and continued indefinitely every 21 days after 6 cycles of cytotoxic therapy are completed and until progression of the disease or prohibitive toxicities occur. 50% of patients will receive Carboplatin/Paclitaxel with the addition of Trastuzumab.

Other Name: Herceptin

Outcome Measures

Primary Outcome Measures :

Progression Free Survival Differences Between Treatment Arms. [ Time Frame: 6 years ]
Progression free survival differences between treatment arms.

Secondary Outcome Measures :

To Assess the Safety Profile of Trastuzumab in USPC Patients by CTCAE v4.0 [ Time Frame: 6 years ]
To assess the safety profile of trastuzumab in USPC patients by CTCAE v4.0. Presented are counts of those that experience any Serious Adverse Events or All Other Adverse Events.
To Assess Objective Response Rate (ORR) [ Time Frame: 6 years ]
To assess objective response rate (ORR)
To Assess Overall Survival (OS) [ Time Frame: 6 years ]
To assess overall survival (OS), presented are the number of participants that survived through the duration of the study period.

Eligibility Criteria

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Ages Eligible for Study:	Child, Adult, Older Adult
Sexes Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients must have advanced (stage III-IV) or recurrent histologically confirmed USPC with measurable disease.
Patients must harbor a tumor HER2/neu+ based upon IHC staining score of 3+ or 2+ with confirmed gene amplification by FISH

Exclusion Criteria:

Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancers, significant history of cardiac disease, uncontrolled hypertension, unstable medical issue, brain leptomeningeal, prior therapy with trastuzumab, uncontrolled seizure disorder, seropositive for HIV, active hepatitis, hemorrhagic diathesis or requiring supplemental oxygen.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01367002

Locations

Show 20 study locations

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United States, Arizona
St. Joseph's Hospital and Medical Center
Phoenix, Arizona, United States, 85013
University of Arizona Cancer Center
Tucson, Arizona, United States, 85724
United States, California
John Muir Clinical Research Center
Concord, California, United States, 94520
Women's Cancer Research Foundation
Newport Beach, California, United States, 92663
United States, Colorado
Penrose St. Francis Hospital
Colorado Springs, Colorado, United States, 80907
United States, Connecticut
Danbury Hospital
Danbury, Connecticut, United States, 06810
University of Connecticut Health Center
Farmington, Connecticut, United States, 06030
The Hospital of Central Connecticut
New Britain, Connecticut, United States, 06050
Smilow Cancer Hospital at Yale New Haven
New Haven, Connecticut, United States, 06510
United States, Illinois
The University of Chicago Medicine
Chicago, Illinois, United States, 60637
United States, Maryland
Greater Baltimore Medical Center
Baltimore, Maryland, United States, 21204
Walter Reed National Military Medical Center
Bethesda, Maryland, United States, 20889-5600
Holy Cross Hospital
Silver Spring, Maryland, United States, 20910
University of Maryland Medical Center
Silver Spring, Maryland, United States, 20910
United States, New Jersey
Jersey Shore University Medical Center
Neptune, New Jersey, United States, 07753
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10461
United States, North Carolina
Duke University School of Medicine
Durham, North Carolina, United States, 27710
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
The Ohio State University
Hilliard, Ohio, United States, 43026
United States, Virginia
University of Virginia
Charlottesville, Virginia, United States, 22908

Sponsors and Collaborators

Yale University

Genentech, Inc.

Investigators

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Principal Investigator:	Alessandro D Santin, M.D.	Yale University

Study Documents (Full-Text)

Documents provided by Yale University:

Study Protocol and Statistical Analysis Plan [PDF] May 6, 2020

More Information

Publications of Results:

Fader AN, Roque DM, Siegel E, Buza N, Hui P, Abdelghany O, Chambers SK, Secord AA, Havrilesky L, O'Malley DM, Backes F, Nevadunsky N, Edraki B, Pikaart D, Lowery W, ElSahwi KS, Celano P, Bellone S, Azodi M, Litkouhi B, Ratner E, Silasi DA, Schwartz PE, Santin AD. Randomized Phase II Trial of Carboplatin-Paclitaxel Versus Carboplatin-Paclitaxel-Trastuzumab in Uterine Serous Carcinomas That Overexpress Human Epidermal Growth Factor Receptor 2/neu. J Clin Oncol. 2018 Jul 10;36(20):2044-2051. doi: 10.1200/JCO.2017.76.5966. Epub 2018 Mar 27.

Fader AN, Roque DM, Siegel E, Buza N, Hui P, Abdelghany O, Chambers S, Secord AA, Havrilesky L, O'Malley DM, Backes FJ, Nevadunsky N, Edraki B, Pikaart D, Lowery W, ElSahwi K, Celano P, Bellone S, Azodi M, Litkouhi B, Ratner E, Silasi DA, Schwartz PE, Santin AD. Randomized Phase II Trial of Carboplatin-Paclitaxel Compared with Carboplatin-Paclitaxel-Trastuzumab in Advanced (Stage III-IV) or Recurrent Uterine Serous Carcinomas that Overexpress Her2/Neu (NCT01367002): Updated Overall Survival Analysis. Clin Cancer Res. 2020 Aug 1;26(15):3928-3935. doi: 10.1158/1078-0432.CCR-20-0953. Epub 2020 Jun 29.

Other Publications:

Santin AD, Bellone S, Gokden M, Palmieri M, Dunn D, Agha J, Roman JJ, Hutchins L, Pecorelli S, O'Brien T, Cannon MJ, Parham GP. Overexpression of HER-2/neu in uterine serous papillary cancer. Clin Cancer Res. 2002 May;8(5):1271-9.

Santin AD, Bellone S, Siegel ER, Palmieri M, Thomas M, Cannon MJ, Kay HH, Roman JJ, Burnett A, Pecorelli S. Racial differences in the overexpression of epidermal growth factor type II receptor (HER2/neu): a major prognostic indicator in uterine serous papillary cancer. Am J Obstet Gynecol. 2005 Mar;192(3):813-8. doi: 10.1016/j.ajog.2004.10.605.

Santin AD, Bellone S, Van Stedum S, Bushen W, De Las Casas LE, Korourian S, Tian E, Roman JJ, Burnett A, Pecorelli S. Determination of HER2/neu status in uterine serous papillary carcinoma: Comparative analysis of immunohistochemistry and fluorescence in situ hybridization. Gynecol Oncol. 2005 Jul;98(1):24-30. doi: 10.1016/j.ygyno.2005.03.041.

Santin AD. Letter to the Editor referring to the manuscript entitled: "Phase II trial of trastuzumab in women with advanced or recurrent HER-positive endometrial carcinoma: a Gynecologic Oncology Group study" recently reported by Fleming et al., (Gynecol Oncol., 116;15-20;2010). Gynecol Oncol. 2010 Jul;118(1):95-6; author reply 96-7. doi: 10.1016/j.ygyno.2010.01.043. Epub 2010 Feb 20. No abstract available.

Schwartz PE. The management of serous papillary uterine cancer. Curr Opin Oncol. 2006 Sep;18(5):494-9. doi: 10.1097/01.cco.0000239890.36408.75.

Cirisano FD Jr, Robboy SJ, Dodge RK, Bentley RC, Krigman HR, Synan IS, Soper JT, Clarke-Pearson DL. The outcome of stage I-II clinically and surgically staged papillary serous and clear cell endometrial cancers when compared with endometrioid carcinoma. Gynecol Oncol. 2000 Apr;77(1):55-65. doi: 10.1006/gyno.2000.5737.

Goff BA, Kato D, Schmidt RA, Ek M, Ferry JA, Muntz HG, Cain JM, Tamimi HK, Figge DC, Greer BE. Uterine papillary serous carcinoma: patterns of metastatic spread. Gynecol Oncol. 1994 Sep;54(3):264-8. doi: 10.1006/gyno.1994.1208.

Randall ME, Filiaci VL, Muss H, Spirtos NM, Mannel RS, Fowler J, Thigpen JT, Benda JA; Gynecologic Oncology Group Study. Randomized phase III trial of whole-abdominal irradiation versus doxorubicin and cisplatin chemotherapy in advanced endometrial carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol. 2006 Jan 1;24(1):36-44. doi: 10.1200/JCO.2004.00.7617. Epub 2005 Dec 5.

Burke TW, Gershenson DM, Morris M, Stringer CA, Levenback C, Tortolero-Luna G, Baker VV. Postoperative adjuvant cisplatin, doxorubicin, and cyclophosphamide (PAC) chemotherapy in women with high-risk endometrial carcinoma. Gynecol Oncol. 1994 Oct;55(1):47-50. doi: 10.1006/gyno.1994.1245.

Levenback C, Burke TW, Silva E, Morris M, Gershenson DM, Kavanagh JJ, Wharton JT. Uterine papillary serous carcinoma (UPSC) treated with cisplatin, doxorubicin, and cyclophosphamide (PAC). Gynecol Oncol. 1992 Sep;46(3):317-21. doi: 10.1016/0090-8258(92)90224-7.

Ball HG, Blessing JA, Lentz SS, Mutch DG. A phase II trial of paclitaxel in patients with advanced or recurrent adenocarcinoma of the endometrium: a Gynecologic Oncology Group study. Gynecol Oncol. 1996 Aug;62(2):278-81. doi: 10.1006/gyno.1996.0227.

Lincoln S, Blessing JA, Lee RB, Rocereto TF. Activity of paclitaxel as second-line chemotherapy in endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2003 Mar;88(3):277-81. doi: 10.1016/s0090-8258(02)00068-9.

Fleming GF, Brunetto VL, Cella D, Look KY, Reid GC, Munkarah AR, Kline R, Burger RA, Goodman A, Burks RT. Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol. 2004 Jun 1;22(11):2159-66. doi: 10.1200/JCO.2004.07.184.

Ramondetta L, Burke TW, Levenback C, Bevers M, Bodurka-Bevers D, Gershenson DM. Treatment of uterine papillary serous carcinoma with paclitaxel. Gynecol Oncol. 2001 Jul;82(1):156-61. doi: 10.1006/gyno.2001.6211.

Creasman WT, Morrow CP, Bundy BN, Homesley HD, Graham JE, Heller PB. Surgical pathologic spread patterns of endometrial cancer. A Gynecologic Oncology Group Study. Cancer. 1987 Oct 15;60(8 Suppl):2035-41. doi: 10.1002/1097-0142(19901015)60:8+3.0.co;2-8.

Tymon-Rosario J, Siegel ER, Bellone S, Harold J, Adjei N, Zeybek B, Mauricio D, Altwerger G, Menderes G, Ratner E, Clark M, Andikyan V, Huang GS, Azodi M, Schwartz PE, Fader AN, Santin AD. Trastuzumab tolerability in the treatment of advanced (stage III-IV) or recurrent uterine serous carcinomas that overexpress HER2/neu. Gynecol Oncol. 2021 Oct;163(1):93-99. doi: 10.1016/j.ygyno.2021.07.033. Epub 2021 Aug 6.

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Responsible Party:	Yale University
ClinicalTrials.gov Identifier:	NCT01367002
Other Study ID Numbers:	1012007786
First Posted:	June 6, 2011 Key Record Dates
Results First Posted:	April 18, 2023
Last Update Posted:	May 17, 2023
Last Verified:	May 2023

Keywords provided by Yale University:


Uterine serous papillary carcinoma Type II endometrial cancer HER2/neu Paclitaxel, Carboplatin, Trastuzumab

Additional relevant MeSH terms:

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Endometrial Neoplasms Uterine Neoplasms Genital Neoplasms, Female Urogenital Neoplasms Neoplasms by Site Neoplasms Uterine Diseases Genital Diseases, Female Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Urogenital Diseases	Genital Diseases Paclitaxel Carboplatin Trastuzumab Antineoplastic Agents, Phytogenic Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Immunological

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