Clinical trial NCT01367002: Evaluation of Carboplatin/Paclitaxel With and Without Trastuzumab (Herceptin) in Uterine Serous Cancer
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Endometrial Cancer
Keywords: Uterine serous papillary carcinoma
Type II endometrial cancer
HER2/neu
Paclitaxel, Carboplatin, Trastuzumab
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2011-06-06
Enrollment: 61
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Eligibility 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.

Primary outcomes:
measure: Progression Free Survival Differences Between Treatment Arms.
timeFrame: 6 years
Secondary outcomes:
measure: To Assess the Safety Profile of Trastuzumab in USPC Patients by CTCAE v4.0
timeFrame: 6 years
measure: To Assess Objective Response Rate (ORR)
timeFrame: 6 years
measure: To Assess Overall Survival (OS)
timeFrame: 6 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: St. Joseph's Hospital and Medical Center
state: Arizona
city: Tucson
country: United States
facility: University of Arizona Cancer Center
state: Arizona
city: Concord
country: United States
facility: John Muir Clinical Research Center
state: California
city: Newport Beach
country: United States
facility: Women's Cancer Research Foundation
state: California
city: Colorado Springs
country: United States
facility: Penrose St. Francis Hospital
state: Colorado
city: Danbury
country: United States
facility: Danbury Hospital
state: Connecticut
city: Farmington
country: United States
facility: University of Connecticut Health Center
state: Connecticut
city: New Britain
country: United States
facility: The Hospital of Central Connecticut
state: Connecticut
city: New Haven
country: United States
facility: Smilow Cancer Hospital at Yale New Haven
state: Connecticut
city: Chicago
country: United States
facility: The University of Chicago Medicine
state: Illinois
city: Baltimore
country: United States
facility: Greater Baltimore Medical Center
state: Maryland
city: Bethesda
country: United States
facility: Walter Reed National Military Medical Center
state: Maryland
city: Silver Spring
country: United States
facility: Holy Cross Hospital
state: Maryland
city: Silver Spring
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Neptune
country: United States
facility: Jersey Shore University Medical Center
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Durham
country: United States
facility: Duke University School of Medicine
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Hilliard
country: United States
facility: The Ohio State University
state: Ohio
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
Study officials:
affiliation: Yale University
name: Alessandro D Santin, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.