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Trial record 1 of 1 for:    05256225
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Testing the Addition of Trastuzumab or Trastuzumab/Pertuzumab to the Usual Chemotherapy for HER2 Positive Endometrial Serous Carcinoma or Carcinosarcoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05256225
Recruitment Status : Recruiting
First Posted : February 25, 2022
Last Update Posted : December 1, 2022
Sponsor:
Collaborator:
NRG Oncology
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This phase II/III trial tests whether adding trastuzumab and hyaluronidase-oysk (Herceptin HylectaTM) or pertuzumab, trastuzumab and hyaluronidase-zzxf (PhesgoTM) to the usual chemotherapy (paclitaxel and carboplatin) works to shrink tumors in patients with HER2 positive endometrial serous carcinoma or carcinosarcoma. Trastuzumab and pertuzumab are monoclonal antibodies and forms of targeted therapy that attach to specific molecules (receptors) on the surface of tumor cells, known as HER2 receptors. When trastuzumab or pertuzumab attach to HER2 receptors, the signals that tell the cells to grow are blocked and the tumor cell may be marked for destruction by the body's immune system. Hyaluronidase is an endoglycosidase. It helps to keep pertuzumab and trastuzumab in the body longer, so that these medications will have a greater effect. Hyaluronidase also allows trastuzumab and trastuzumab/pertuzumab to be given by injection under the skin and shortens their administration time compared to trastuzumab or pertuzumab alone. Paclitaxel is a taxane and in a class of medications called antimicrotubule agents. It stops cancer cells from growing and dividing and may kill them. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Giving Herceptin Hylecta or Phesgo in combination with paclitaxel and carboplatin may shrink the tumor and prevent the cancer from coming back in patients with HER2 positive endometrial serous carcinoma or carcinosarcoma.

Condition or disease Intervention/treatment Phase
Endometrial Serous Adenocarcinoma Uterine Corpus Carcinosarcoma Drug: Carboplatin Procedure: Echocardiography Drug: Hyaluronidase-zzxf/Pertuzumab/Trastuzumab Procedure: Multigated Acquisition Scan Drug: Paclitaxel Other: Quality-of-Life Assessment Drug: Trastuzumab/Hyaluronidase-oysk Phase 2 Phase 3

Show Show detailed description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 525 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II/III Study of Paclitaxel/Carboplatin Alone or Combined With Either Trastuzumab and Hyaluronidase-Oysk (HERCEPTIN HYLECTA) or Pertuzumab, Trastuzumab, and Hyaluronidase-Zzxf (PHESGO) in HER2 Positive, Stage I-IV Endometrial Serous Carcinoma or Carcinosarcoma
Actual Study Start Date : August 12, 2022
Estimated Primary Completion Date : October 31, 2027
Estimated Study Completion Date : October 31, 2027


Arm Intervention/treatment
Active Comparator: Arm I (paclitaxel, carboplatin)

Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease after completion of cycle 6 may receive 4 additional cycles of this treatment at the discretion of the treating physician.

Patients undergo ECHO or MUGA scan at end of treatment and every 6 months for 2 years.

Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carboplatinum
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo

Procedure: Echocardiography
Undergo ECHO
Other Name: EC

Procedure: Multigated Acquisition Scan
Undergo MUGA
Other Names:
  • Blood Pool Scan
  • Equilibrium Radionuclide Angiography
  • Gated Blood Pool Imaging
  • MUGA
  • Radionuclide Ventriculography
  • RNVG
  • SYMA Scanning
  • Synchronized Multigated Acquisition Scanning

Drug: Paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Experimental: Arm II (paclitaxel, carboplatin, Herceptin Hylecta)

Patients receive paclitaxel IV over 3 hours, carboplatin IV over 30-60 minutes, and trastuzumab/hyaluronidase-oysk SC over 2-5 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease after completion of cycle 6 may receive 4 additional cycles of this treatment at the discretion of the treating physician.

MAINTENANCE: Patients receive trastuzumab/hyaluronidase-oysk SC over 2-5 minutes on day 1 of each cycle. Cycles repeat every 3 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients with SD or PR may continue maintenance therapy for up to 3 years from the start of treatment.

Patients undergo ECHO or MUGA scan at end of treatment and every 6 months for 2 years.

Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carboplatinum
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo

Procedure: Echocardiography
Undergo ECHO
Other Name: EC

Procedure: Multigated Acquisition Scan
Undergo MUGA
Other Names:
  • Blood Pool Scan
  • Equilibrium Radionuclide Angiography
  • Gated Blood Pool Imaging
  • MUGA
  • Radionuclide Ventriculography
  • RNVG
  • SYMA Scanning
  • Synchronized Multigated Acquisition Scanning

Drug: Paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Drug: Trastuzumab/Hyaluronidase-oysk
Given SC
Other Names:
  • Herceptin Hylecta
  • Trastuzumab and Hyaluronidase-oysk
  • Trastuzumab and Recombinant Human Hyaluronidase PH20
  • Trastuzumab and rHuPH20
  • Trastuzumab-Hyaluronidase-oysk

Experimental: Arm III (paclitaxel, carboplatin, Phesgo)

Patients receive paclitaxel IV over 3 hours, carboplatin IV over 30-60 minutes, and pertuzumab/trastuzumab/hyaluronidase-zzxf SC over 5-8 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease after completion of cycle 6 may receive 4 additional cycles of this treatment at the discretion of the treating physician.

MAINTENANCE: Patients receive pertuzumab/trastuzumab/ hyaluronidase-zzxf SC over 5 minutes on day 1. Cycles repeat every 3 weeks for up to 1 year in absence of disease progression or unacceptable toxicity. Patients with SD or PR may continue maintenance for up to 3 years from the start of treatment.

Patients undergo ECHO or MUGA scan at end of treatment and every 6 months for 2 years.

Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carboplatinum
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo

Procedure: Echocardiography
Undergo ECHO
Other Name: EC

Drug: Hyaluronidase-zzxf/Pertuzumab/Trastuzumab
Given SC
Other Names:
  • Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf
  • Pertuzumab/Trastuzumab/Hyaluronidase-zzxf
  • Phesgo

Procedure: Multigated Acquisition Scan
Undergo MUGA
Other Names:
  • Blood Pool Scan
  • Equilibrium Radionuclide Angiography
  • Gated Blood Pool Imaging
  • MUGA
  • Radionuclide Ventriculography
  • RNVG
  • SYMA Scanning
  • Synchronized Multigated Acquisition Scanning

Drug: Paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment




Primary Outcome Measures :
  1. Progression free survival (Phase II) [ Time Frame: From study entry to time of progression or death, whichever occurs first, or date of last contact if neither progression nor death has occurred, assessed up to 5 years from randomization ]
    At the end of Phase 2 analysis, if both experimental arms demonstrate superiority to the reference, the experimental arms will be compared to each other.

  2. Incidence of dose limiting toxicities (Phase II) [ Time Frame: Up to end of cycle 3 (week 12) ]
    A dose limiting toxicity is any treatment-related adverse event requiring permanent discontinuation of the experimental therapy prior to the completion of treatment cycle 3.

  3. Overall survival (Phase III) [ Time Frame: From study entry to time of death or the date of last contact, assessed up to 5 years from randomization ]
    If both experimental arms demonstrate superiority to the reference arm, the experimental arms will be compared to each other.


Secondary Outcome Measures :
  1. Objective response rate (ORR) [ Time Frame: Within 12 months of initiating maintenance therapy ]
    Defined as the binomial proportion of evaluable patients with a best overall response of complete response (CR) or partial response (PR) (by Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) within 12 months of initiating maintenance therapy. Responses reported by the treating physician will be used for these analyses. The ORR estimates by treatment arm will be supported by their 2-sided, 95% Wilson-Score confidence intervals (Wilson, 1927; Agresti, 1998). The relative odds of response in each experimental group (vs the reference group) will be estimated using a multivariable logistic regression model specified with main effects for the treatment groups and covariate adjustments for the stratification factors reported at baseline.

  2. Duration of objective response [ Time Frame: From documentation of either PR or CR until disease progression or death, whichever is observed first, assessed up to 5 years from randomization ]
    Treatment group differences in response duration will be graphed using Kaplan-Meier methods and compared using logrank tests, stratified by the minimization factors defined at randomization. The relative hazards of progression or death in each experimental group (vs the reference group) will be estimated using a multivariable proportional hazards regression model specified with main effects for the treatment indicators and covariate adjustments for the stratification factors reported at baseline.

  3. Incidence of adverse events (AEs) [ Time Frame: Up to 5 years from randomization ]
    The nature, frequency, and degree of toxicity will be tabulated at the System Organ Class and AE-specific term levels using Common Terminology Criteria (CTCAE) version 5.0. Each patient will be represented according to the maximum grade observed for each term. Tabulations will show the number and percentage of patients by maximum grade, within the treatment group received, regardless of the randomized treatment assignment.

  4. HER2 expression [ Time Frame: Up to 5 years from randomization ]
    Correlation of HER2 immunohistochemistry (IHC) expression and in situ hybridization (ISH) amplification with clinical outcome and response to HER2 targeted therapies will be explored.

  5. Quality of life [ Time Frame: Up to 5 years from randomization ]
    Measured by Functional Assessment of Cancer Therapy - Endometrial Trial Outcome Index (FACT-En-TOI).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Federation of Gynecology and Obstetrics (FIGO) 2009 stage IA-IVB, non-recurrent, chemotherapy (chemo)-naive, HER2-positive endometrial serous carcinoma or endometrial carcinosarcoma
  • Histologic confirmation of the original primary tumor is required. Submission of surgical pathology report (or endometrial biopsy pathology report in patients who never undergo hysterectomy) is required
  • Patients must be within 8 weeks of primary surgery (or endometrial biopsy in patients who never undergo hysterectomy) at the time of study registration
  • Patients may have measurable disease, non-measurable disease, or no measurable disease. In patients with measurable disease, lesions will be defined and monitored by RECIST v 1.1. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be >= 10 mm when measured by computed tomography (CT) or magnetic resonance imaging (MRI). Lymph nodes must be >= 15 mm in short axis when measured by CT or MRI
  • For patients with uterine-confined (stage I) disease, the tumor must be invasive into the myometrium. Any amount of myoinvasion is acceptable for eligibility. Patients with non-invasive disease, endometrial intraepithelial carcinoma alone, or disease confined to a polyp will be excluded
  • Additionally, patients must have the following histologic types to be eligible:

    • Serous adenocarcinoma (may include =< 10% non-serous histology)
    • Carcinosarcoma with serous epithelial component (only the serous component needs to be HER2 positive; may include =< 10% non-serous histology)
    • In cases where determination of serous is equivocal or challenging, aberrant p53 immunohistochemistry (IHC) (defined as overexpression of p53 compared to internal controls) will be sufficient for inclusion
  • All patients must have tumors that are HER2 positive as defined by American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) 2018 Breast Cancer guidelines (https://documents.cap.org/documents/algorithim-evaluation-her2.pdf. In general HER2 positivity is defined as any of the following:

    • 3+ immunohistochemistry (IHC),
    • 2+ IHC with positive in situ hybridization (ISH)
    • Average HER2 copy number >= 6.0 signals/cell
    • Average HER2 copy number >= 4.0 and < 6.0 signals/cell, with concurrent IHC 3+
    • HER2/CEP17 ratio >= 4.0 signals/cell
    • HER2/CEP 17 ratio >= 2.0 and < 4.0, with concurrent IHC 3+ IHC and ISH testing will be done locally, at each participating institution and interpreted by local pathologists. Alternatively, patients could be eligible if next generation sequencing (NGS) demonstrates HER2 (ERBB2) amplification. NGS testing can be performed through any designated labs as per the National Cancer Institute (NCI) MATCH/NCI Combo-MATCH trial (https://ecog-acrin.org/nci-match-eay131-designated-labs).

Pathology report showing results of institutional HER2 testing (or NGS testing results) must be submitted.

Sites must submit all results available (IHC, ISH, and NGS)

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
  • Age >= 18
  • Platelets >= 100,000/mcl (within 14 days prior to registration)
  • Absolute neutrophil count (ANC) >= 1,500/mcl (within 14 days prior to registration)
  • Creatinine =< 1.5 x institutional/laboratory upper limit of normal (ULN) or estimated Glomerular filtration rate (eGFR) >= 50 mL/min using either the Cockcroft-Gault equation, the Modification of Diet in Renal Disease Study, or as reported in the comprehensive metabolic panel/basic metabolic panel (eGFR). (within 14 days prior to registration)
  • Total serum bilirubin level =< 1.5 x ULN (patients with known Gilbert's disease who have bilirubin level =< 3 x ULN may be enrolled) (within 14 days prior to registration)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN (within 14 days prior to registration)
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial
  • Although the uterus will have been removed in the vast majority of patients, for patients of child-bearing potential: negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test is required. Patients will be considered of non-reproductive potential if they are either:

    • Postmenopausal (defined as at least 12 months with no menses without an alternative medical cause; in women < 45 years of age, a high follicle stimulating hormone [FSH] level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. In the absence of 12 months of amenorrhea, a single FSH measurement is insufficient); OR
    • Have had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy or bilateral tubal ligation/occlusion at least 6 weeks prior to registration
    • Have a congenital or acquired condition that prevents childbearing
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. NOTE: Patients with prior anthracycline exposure are NOT eligible
  • Patients with evidence of chronic hepatitis B virus (HBV) infection must have an undetectable HBV viral load on suppressive therapy, if indicated
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
  • Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
  • The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information

Exclusion Criteria:

  • Prior Therapy:

    • Patients must NOT have received prior chemotherapy, biologic therapy, or targeted therapy for treatment of endometrial carcinoma
    • Patients must NOT have received prior radiation therapy for treatment of endometrial carcinoma. Prior radiation includes external beam pelvic radiation therapy, external beam extended field pelvic/para-aortic radiation therapy, and/or intravaginal brachytherapy

      • NOTE: Vaginal brachytherapy for treatment of endometrial cancer is permitted during study treatment. Planned use of vaginal brachytherapy must be declared at time of registration
    • Patients may have received prior hormonal therapy for treatment of endometrial carcinoma. All hormonal therapy must be discontinued at least one week prior to registration
  • Patients may not have a planned interval cytoreduction or hysterectomy, prior to documentation of progression, after study registration
  • Patients may not have planned external beam radiotherapy, prior to documentation of progression, after study registration
  • Significant cardiovascular disease including:

    • Uncontrolled hypertension, defined as systolic > 150 mm Hg or diastolic > 90 mm Hg despite antihypertensive medications
    • Myocardial infarction or unstable angina within 6 months prior to registration
    • New York Heart Association functional classification II, III or IV
    • Serious cardiac arrhythmia requiring medication. This does not include asymptomatic, atrial fibrillation with controlled ventricular rate
  • Significant lung disease: dyspnea at rest grade 2 or greater (resulting from extensive tumor involvement or other causes), pneumonitis grade 2 or greater, interstitial lung disease grade 2 or greater, idiopathic pulmonary fibrosis, cystic fibrosis, Aspergillosis, active tuberculosis, or history of opportunistic infections (pneumocystis pneumonia or cytomegalovirus pneumonia)
  • Patients with uncontrolled intercurrent illness including, but not limited to: ongoing or active infection (except for uncomplicated urinary tract infection), uncontrolled interstitial lung disease, symptomatic congestive heart failure, or psychiatric illness/social situations that would limit compliance with study requirements
  • Treatment with strong CYP2C8 or CYP3A4 inhibitors or inducers within 14 days or 5 drug-elimination half-lives, whichever is longer, prior to registration
  • Women who are unwilling to discontinue nursing

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): NCT05256225


Locations
Show Show 93 study locations
Sponsors and Collaborators
National Cancer Institute (NCI)
NRG Oncology
Investigators
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Principal Investigator: Britt K Erickson NRG Oncology
Layout table for additonal information
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT05256225    
Other Study ID Numbers: NCI-2022-01540
NCI-2022-01540 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
NRG-GY026 ( Other Identifier: NRG Oncology )
NRG-GY026 ( Other Identifier: CTEP )
U10CA180868 ( U.S. NIH Grant/Contract )
First Posted: February 25, 2022    Key Record Dates
Last Update Posted: December 1, 2022
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page
URL: https://grants.nih.gov/policy/sharing.htm

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Cystadenocarcinoma, Serous
Carcinosarcoma
Mixed Tumor, Mullerian
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Cystadenocarcinoma
Neoplasms, Cystic, Mucinous, and Serous
Neoplasms, Complex and Mixed
Sarcoma
Neoplasms, Connective and Soft Tissue
Paclitaxel
Carboplatin
Trastuzumab
Albumin-Bound Paclitaxel
Pertuzumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological