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

Description
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.

Objective
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. Efficacy will be determined via investigator assessed progression free survival (PFS) as assessed by RECIST 1.1. The two experimental arms (Arms 2 and 3) will be compared to the reference arm (Arm 1). If the experimental arms demonstrate superiority to the reference, the experimental arms will be compared to each other.
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. Efficacy will be determined via investigator assessed overall survival (OS). The two experimental arms (Arms 2 and 3) will be compared to the reference arm (Arm 1). If the experimental arms demonstrate superiority to the reference, the experimental arms will be compared to each other.
Secondary:
To evaluate the overall response rate (ORR) in patients with measurable disease. The ORR will be defined as the binomial proportion of evaluable patients with a best overall response of CR or PR (by RECIST 1.1) within 12 months of initiating maintenance therapy.
To evaluate the duration of objective response in patients with measurable disease as assessed by RECIST 1.1.
To determine the nature, frequency and degree of toxicity as assessed by CTCAE v.5.0 for each treatment arm.
To compare QOL, as measured by FACT-En-TOI, in the experimental versus control arms.
To compare patient-reported treatment-associated symptoms (diarrhea and rash) as measured with the PRO -CTCAE, patient-reported fatigue as measured with the PROMIS-Fatigue short form, and worry 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.
To assess the correlation of HER2 IHC expression and ISH amplification with clinical
NRG-GY026 - 11 - Version Date: July 11, 2022
outcome and response to HER2 targeted therapies.

Treatment Arm 1 (Control Arm):
Paclitaxel 175 mg/m2 IV over 3 hours Day 1
Carboplatin AUC 5 IV over approximately 30-60 minutes Day 1
Paclitaxel and Carboplatin will be administered every 3 weeks for a total of 6 cycles*

Arm 2
Paclitaxel 175 mg/m2 IV over 3 hours Day 1
Carboplatin AUC 5 IV over approximately 30-60 minutes Day 1
Trastuzumab and hyaluronidase-oysk (HERCEPTIN HYLECTA) 5mL Subq over 2-5
minutes, Day 1
Paclitaxel, Carboplatin and Trastuzumab and hyaluronidase-oysk (HERCEPTIN
HYLECTA) will be administered every 3 weeks for 6 cycles.*

Arm 3:
Please note the Loading Dose and Maintenance Doses (11-JULY-2022)
Cycle 1:
Paclitaxel 175 mg/m2 IV over 3 hours Day 1
Carboplatin AUC 5 IV over approximately 30-60 minutes Day 1
Pertuzumab, trastuzumab, and hyaluronidase-zzxf (PHESGO) LOADING DOSE 15mL
Subq over 5-8 minutes, Day 1
Cycles 2-6:
Paclitaxel 175 mg/m2 IV over 3 hours Day 1
Carboplatin AUC 5 IV over approximately 30-60 minutes Day 1
Pertuzumab, trastuzumab, and hyaluronidase-zzxf

Key Eligibility For full study eligibility, see this study's ClinicalTrials.gov record.

Applicable Disease Sites
Uterus

Participating Institutions
DN Greenwald Center; UW Cancer Center at ProHealth; UW Health Eastpark Medical Center; UW Health University Hospital