Health Trials

Testing the Addition of Herceptin Hylecta or Phesgo to the Usual Chemotherapy for HER2 Positive Endometrial Serous Carcinoma or Carcinosarcoma

ConditionsEndometrial CarcinomaEndometrial Clear Cell AdenocarcinomaEndometrial Dedifferentiated CarcinomaEndometrial Endometrioid AdenocarcinomaEndometrial Mixed Cell AdenocarcinomaEndometrial Serous AdenocarcinomaEndometrial Undifferentiated CarcinomaUterine Corpus Malignant Mixed Mesodermal (Mullerian) Tumor
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexFemale
Age18+
SponsorNational Cancer Institute (NCI)

About this trial

This phase III trial tests whether adding trastuzumab and hyaluronidase-oysk (Herceptin Hylecta \[TM\]) or pertuzumab, trastuzumab and hyaluronidase-zzxf (Phesgo \[TM\]) to the usual chemotherapy (paclitaxel and carboplatin) works to shrink tumors in patients with HER2 positive endometrial cancer. 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 tumor 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 cancer.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Serous

Other endometrial cancers (including clear cell, endometrioid, mixed epithelial, dedifferentiated/undifferentiated)

Carcinosarcoma

NOTE: Endometrial cancers that are mismatch repair deficient (dMMR) by IHC are not eligible

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

  • Biospecimen Collection

    Procedure/Surgery

    Undergo blood and urine sample collection

  • Carboplatin

    Drug

    Given IV

  • Computed Tomography

    Procedure/Surgery

    Undergo CT

  • Echocardiography Test

    Procedure/Surgery

    Undergo ECHO

  • High-Dose-Rate Vaginal Cuff Brachytherapy

    Radiation

    Undergo vaginal brachytherapy

  • Hyaluronidase-zzxf/Pertuzumab/Trastuzumab

    Drug

    Given SC

  • Multigated Acquisition Scan

    Procedure/Surgery

    Undergo MUGA

  • Paclitaxel

    Drug

    Given IV

  • Survey Administration

    Other intervention

    Ancillary studies

  • Trastuzumab/Hyaluronidase-oysk

    Drug

    Given SC

Treatment groups

360 Participants
are divided into 3 treatment groups
Group A: Arm I (paclitaxel, carboplatin)Active comparator 7 interventions
Group B: Arm II (paclitaxel, carboplatin, Herceptin Hylecta)Experimental treatment 9 interventions
Group C: Arm III (paclitaxel, carboplatin, Phesgo)Experimental treatment 9 interventions

Trial outcomes

Primary outcomes

1

Progression free survival

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.

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
2

Overall survival

If both experimental arms demonstrate superiority to the reference arm, the experimental arms will be compared to each other.

Time frame
From study entry to time of death or the date of last contact, assessed up to 5 years from randomization
3

Incidence of dose limiting toxicities

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.

Time frame
Up to end of cycle 3 (week 12)

Secondary outcomes

1

Objective response rate (ORR)

Defined as the binomial proportion of evaluable patients with a best overall response of complete response or partial response (by Response Evaluation Criteria in Solid Tumors 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 (versus \[vs\] 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.

Time frame
Within 12 months of initiating maintenance therapy
2

Duration of objective response

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.

Time frame
From documentation of either partial response or complete response until disease progression or death, whichever is observed first, assessed up to 5 years from randomization
3

Incidence of adverse events (AEs)

The nature, frequency, and degree of toxicity will be tabulated at the System Organ Class and AE-specific term levels using Common Terminology Criteria 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.

Time frame
Up to 5 years from randomization
4

HER2 expression

Correlation of HER2 immunohistochemistry expression and in situ hybridization amplification with clinical outcome and response to HER2 targeted therapies will be explored.

Time frame
Up to 5 years from randomization

Other outcomes

1

QoL deterioration

The deterioration in QoL will be measured by a drop of \>= 6 points in the FACT-En TOI score from baseline and lasting for more than one patient reported outcome time point in experimental and control arms.

Time frame
Baseline up to 5 years

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

National Cancer Institute (NCI)

Lead sponsor

NRG Oncology

Collaborator

Source ClinicalTrials.gov
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