Testing the Addition of Trastuzumab or Trastuzumab/Pertuzumab to the Usual Chemotherapy for HER2 Positive Endometrial Serous Carcinoma or Carcinosarcoma

Active:	Yes
Cancer Type:	Uterine Cancer	NCT ID:	NCT05256225
Trial Phases:	Phase II Phase III	Protocol IDs:	NRG-GY026 (primary) NRG-GY026 NCI-2022-01540
Eligibility:	18 Years and older, Female	Study Type:	Treatment
Study Sponsor:	NRG Oncology
NCI Full Details:	http://clinicaltrials.gov/show/NCT05256225

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.

Objectives

PRIMARY OBJECTIVES:
I. To evaluate the efficacy of trastuzumab and hyaluronidase-oysk (HERCEPTIN HYLECTA) and pertuzumab, trastuzumab, and hyaluronidase-zzxf (PHESGO) in combination with paclitaxel/carboplatin in patients with HER2 positive endometrial serous carcinoma or carcinosarcoma. (Phase II)
II. To evaluate the efficacy of trastuzumab and hyaluronidase-oysk (HERCEPTIN HYLECTA) and pertuzumab, trastuzumab, and hyaluronidase-zzxf (PHESGO) in combination with paclitaxel/carboplatin in patients with HER2 positive endometrial serous carcinoma or carcinosarcoma. (Phase III)

SECONDARY OBJECTIVES:
I. To evaluate the overall response rate (ORR) in patients with measurable disease.
II. To evaluate the duration of objective response in patients with measurable disease as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
III. To determine the nature, frequency and degree of toxicity as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 5.0 for each treatment arm.
IV. To compare quality of life (QOL), as measured by Functional Assessment of Cancer Therapy - Endometrial Trial Outcome Index (FACT-En-TOI), in the experimental versus control arms.
V. To compare patient-reported treatment-associated symptoms (diarrhea and rash) as measured with the Patient Reported Outcomes (PRO) - CTCAE, patient-reported fatigue as measured with the Patient Reported Outcomes Measurement Information System (PROMIS)-Fatigue short form, and other concerning side effects of treatment as measured by the item ‘bothered by side effect’, in the FACT-En TOI, respectively, in the experimental and control arms.
VI. To assess the correlation of HER2 immunohistochemistry (IHC) expression and in situ hybridization (ISH) amplification with clinical outcome and response to HER2 targeted therapies.

EXPLORATORY OBJECTIVE:
I. To explore time to sustained deterioration in quality of life, as measured by a drop in the FACT-En-TOI by 6 or more points lasting for more than one PRO time point, in the experimental and control arms.

OUTLINE: Patients are randomized to 1 of 3 arms.

ARM I: Patients receive paclitaxel intravenously (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 stable disease (SD) or partial response (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.

ARM II: Patients receive paclitaxel IV over 3 hours, carboplatin IV over 30-60 minutes, and trastuzumab/hyaluronidase-oysk subcutaneously (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.

ARM III: 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 echocardiography (ECHO) or multigated acquisition scan (MUGA) and computed tomography (CT) throughout the study and optionally undergo blood sample collection prior to treatment and prior to the first cycle of maintenance therapy and urine sample collection prior to treatment.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Treatment Sites in Georgia

Bluffton Campus at St. Joseph's/Candler
100 Buckwalter Place Blvd
Bluffton, SC 29110

St. Joseph's /Candler Health System, INC
5353 Reynolds Street
Savannah, GA 31405
912-819-5723

St. Joseph's /Candler Health System, INC
11705 Mercy Blvd
Savannah, GA 31419

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