Herceptin Hylecta or Phesgo + Chemotherapy for Uterine Cancer

Recruiting at 435 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP2C8, CYP3A4

Disqualifiers: Uncontrolled hypertension, Cardiovascular disease, Lung disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 37

Duration: 18-30 weeks

360 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new methods to treat HER2 positive endometrial cancer by adding targeted therapies to standard chemotherapy. Researchers aim to determine if combining Herceptin Hylecta or Phesgo with paclitaxel and carboplatin can more effectively shrink tumors and prevent cancer recurrence. The trial seeks participants with HER2 positive endometrial cancer who have not previously received chemotherapy for it. Those within eight weeks of primary surgery may be suitable candidates for this study. As a Phase 3 trial, it represents the final step before FDA approval, providing an opportunity to access potentially effective treatments early.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but you must stop any hormonal therapy at least one week before joining. Also, you cannot take strong CYP2C8 or CYP3A4 inhibitors or inducers within 14 days before joining.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that Herceptin Hylecta and Phesgo, when combined with chemotherapy drugs like paclitaxel and carboplatin, yield promising safety results. Herceptin Hylecta, a mix of trastuzumab and hyaluronidase, has already received approval for certain breast cancers, indicating it has passed safety checks for that use. Studies have found that adding trastuzumab to chemotherapy for uterine cancer patients did not significantly increase side effects compared to chemotherapy alone.

Phesgo, which combines pertuzumab, trastuzumab, and hyaluronidase, has been studied in breast cancer patients. These studies found it was generally well-tolerated, with most side effects being mild to moderate, such as tiredness or nausea, while serious side effects were less common.

Both Herceptin Hylecta and Phesgo are designed for longer retention in the body and are administered by injection under the skin. This method can be more convenient and quicker than traditional IV treatments. Overall, evidence suggests these treatments are reasonably safe to use with standard chemotherapy, with manageable side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for uterine cancer because they integrate innovative drug combinations with new delivery methods. Herceptin Hylecta and Phesgo combine trastuzumab with hyaluronidase, allowing for faster subcutaneous injections, which can be more convenient and comfortable compared to traditional intravenous delivery. Additionally, Phesgo includes pertuzumab, which targets HER2-positive cancer cells, potentially enhancing the treatment's effectiveness. These features could offer a more efficient and patient-friendly alternative to standard treatments like chemotherapy, which typically involve lengthy IV sessions.

What evidence suggests that this trial's treatments could be effective for HER2 positive endometrial cancer?

This trial will compare the effectiveness of different treatment combinations for HER2 positive endometrial cancer. Studies have shown that adding Herceptin Hylecta, which participants in Arm II may receive, or Phesgo, which participants in Arm III may receive, to the usual chemotherapy drugs, paclitaxel and carboplatin, can help shrink tumors. These treatments target specific proteins called HER2 receptors on cancer cells, stopping their growth and signaling the immune system to destroy them. Earlier research using trastuzumab, a key component of both Herceptin Hylecta and Phesgo, showed benefits in treating advanced stages of HER2 positive cancers. Combining these treatments with chemotherapy aims to lower the risk of cancer recurrence. Overall, these findings offer strong hope for better outcomes in managing this type of cancer. ^{2 6 7 8 9}

Who Is on the Research Team?

Britt K Erickson

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

This trial is for adults with HER2 positive endometrial serous carcinoma or carcinosarcoma who've had surgery within the last 8 weeks. They should not have received prior treatments for their cancer and must be in good health with proper organ function. Women of childbearing potential must test negative for pregnancy, and those with HIV or hepatitis B/C need controlled viral loads.

Inclusion Criteria

My tumor is HER2 positive according to the latest guidelines.

Platelets >= 100,000/mcl

My cancer can be measured by scans or may not be visible on scans.

Exclusion Criteria

I haven't taken strong medication that affects drug metabolism in the last 14 days or longer.

I have not had a heart attack or unstable heart pain in the last 6 months.

I have not had radiation therapy for endometrial cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive paclitaxel and carboplatin, with or without trastuzumab/hyaluronidase-oysk or pertuzumab/trastuzumab/hyaluronidase-zzxf, every 3 weeks for 6 cycles. Additional cycles may be given if disease is stable or partially responsive.

18-30 weeks

6-10 visits (in-person)

Maintenance

Patients receive maintenance therapy with trastuzumab/hyaluronidase-oysk or pertuzumab/trastuzumab/hyaluronidase-zzxf every 3 weeks for up to 1 year, extendable to 3 years if stable or partially responsive.

1-3 years

17-52 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up every 3 months for 2 years, then every 6 months for 3 years.

5 years

14 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Paclitaxel
• Pertuzumab
• Trastuzumab

Trial Overview The study tests adding Herceptin Hylecta (trastuzumab/hyaluronidase-oysk) or Phesgo (pertuzumab/trastuzumab/hyaluronidase-zzxf) to standard chemotherapy (paclitaxel/carboplatin). These drugs target specific receptors on tumor cells to block growth signals and mark them for immune destruction, potentially shrinking tumors more effectively.

How Is the Trial Designed?

Group I: Arm III (paclitaxel, carboplatin, Phesgo) Experimental Treatment 9 Interventions

See Detailed Description.

Group II: Arm II (paclitaxel, carboplatin, Herceptin Hylecta) Experimental Treatment 9 Interventions

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. Cycles repeat 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 and CT throughout the study. Additionally patients may optionally undergo blood sample collection throughout the study, vaginal brachytherapy on study, and urine sample collection prior to treatment.

Group III: Arm I (paclitaxel, carboplatin) Active Control 7 Interventions

Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30-60 minutes on day 1 of each cycle. Cycles repeat 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 and CT throughout the study. Additionally, patients may optionally undergo blood sample collection throughout the study, vaginal brachytherapy on study, and urine sample collection prior to treatment.

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

NRG Oncology

Collaborator

Trials

242

Recruited

105,000+

Published Research Related to This Trial

The combination of paclitaxel and carboplatin showed promising activity in treating endometrial cancer resistant to standard therapies, with 63% of evaluable patients experiencing a significant reduction in tumor size.

While the treatment had acceptable toxicity levels, with some patients experiencing grade 3 or 4 hematologic issues, further follow-up is needed to assess long-term survival outcomes and the overall effectiveness of this regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A trial of outpatient paclitaxel and carboplatin for advanced, recurrent, and histologic high-risk endometrial carcinoma: preliminary report. Price, FV., Edwards, RP., Kelley, JL., et al.[2016]

In a study of 39 patients with metastatic or recurrent endometrial carcinoma, the combination of paclitaxel, topotecan, and carboplatin resulted in a 60% objective clinical response rate, indicating significant efficacy in treating this cancer.

The treatment was associated with manageable toxicity, with only 13% of patients experiencing severe thrombocytopenia and 10% experiencing severe neutropenia, suggesting that the regimen is relatively safe for outpatient use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel, topotecan, and carboplatin in metastatic endometrial cancinoma: a Hellenic Co-operative Oncology Group (HeCOG) study. Papadimitriou, CA., Fountzilas, G., Bafaloukos, D., et al.[2015]

In a pilot study of 15 patients with uterine serous carcinoma, topotecan showed promising results as a treatment, with 80% of patients completing the protocol and a median progression-free survival of 25 months.

Despite some serious side effects like grade 3 neutropenia and anemia, the outcomes were encouraging, with 9 out of 11 first-line patients alive at follow-up and 5 being disease-free, suggesting that topotecan may be a viable option for this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study of topotecan in the treatment of serous carcinoma of the uterus. Chambers, JT., Rutherford, TJ., Schwartz, PE., et al.[2019]

In a phase II trial involving 61 patients with advanced or recurrent uterine serous carcinoma, adding trastuzumab to carboplatin-paclitaxel significantly improved progression-free survival from 8.0 months to 12.6 months, indicating enhanced treatment efficacy.

The combination treatment was well tolerated, with no significant differences in toxicity between the two groups, suggesting that trastuzumab can be safely integrated into the treatment regimen for patients with HER2/neu-positive uterine serous carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Phase II Trial of Carboplatin-Paclitaxel Versus Carboplatin-Paclitaxel-Trastuzumab in Uterine Serous Carcinomas That Overexpress Human Epidermal Growth Factor Receptor 2/neu. Fader, AN., Roque, DM., Siegel, E., et al.[2022]

In a study of 47 patients with advanced endometrial cancer, the combination of paclitaxel, carboplatin, and amifostine resulted in a total response rate of 40%, with a median progression-free survival of 7 months and median overall survival of 14 months.

The treatment was generally well tolerated, with manageable toxicity; although 79% of patients experienced Grade 3/4 neutropenia, there were no severe cases of febrile neutropenia, indicating a favorable safety profile for this chemotherapy regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel and carboplatin with amifostine in advanced, recurrent, or refractory endometrial adenocarcinoma: a phase II study of the Southwest Oncology Group. Scudder, SA., Liu, PY., Wilczynski, SP., et al.[2015]

The recommended dosage for TEC chemotherapy (paclitaxel, epirubicin, and carboplatin) was established as tolerable, showing a response rate of 74% and a median overall survival of 37 months for patients with advanced primary endometrial carcinoma.

Adjuvant TEC therapy significantly improved prognosis compared to radiation therapy in completely resected stage III endometrial cancer cases, indicating its effectiveness as both a remission-induction and adjuvant treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy for endometrial carcinoma (GOGO-EM1 study): TEC (paclitaxel, epirubicin, and carboplatin) is an effective remission-induction and adjuvant therapy. Egawa-Takata, T., Ueda, Y., Kuragaki, C., et al.[2015]

In a study of 18 patients with advanced or recurrent endometrial cancer, the combination of carboplatin and paclitaxel showed a high overall response rate of 63%, with 35% achieving a complete response.

The treatment demonstrated minimal toxicity, as no patients experienced severe side effects like neutropenia or significant vomiting, and the median survival time was 27 months, indicating it is a promising option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin and paclitaxel for the treatment of advanced or recurrent endometrial cancer. Akram, T., Maseelall, P., Fanning, J.[2015]

In a study of 24 patients with metastatic or recurrent endometrial cancer, the combination of tislelizumab with carboplatin-paclitaxel showed a promising objective response rate of 62.5%, indicating effective treatment for this challenging condition.

The treatment was found to be safe, with no allergic reactions or treatment-related deaths reported, although half of the patients experienced moderate to severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab Combined with Carboplatin-Paclitaxel for Treatment of Metastatic or Recurrent Endometrial Cancer: a Retrospective Clinical Study. Gao, FF., Zhang, XL., Chen, JL., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05256225

NCT05256225 | Testing the Addition of Herceptin Hylecta ... 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 ...

2. nrgoncology.org nrgoncology.org/Home/News/Post/testing-the-addition-of-trastuzumab-or-trastuzumabpertuzumab-to-the-usual-chemotherapy-for-her2-positive-uterine-serous-or-carcinosarcoma-nrg-gy026

Testing the addition of trastuzumab or ... Phase II data has demonstrated a benefit from adding trastuzumab (a monoclonal antibody directed at HER2)in HER2 positive advanced and recurrent ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-01540

Testing the addition of Herceptin Hylecta or Phesgo to ... 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 ...

4. phesgo.com phesgo.com/about-phesgo/clinical-trial-results.html

Clinical trial results with PHESGO® (pertuzumab ... The combined results of the study showed that there were no major differences between PHESGO and IV PERJETA + Herceptin. *Some patients in the trial were given ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12215578/

Drug discovery in advanced and recurrent endometrial cancer The study reported an ORR of 14.3% (95% CI 8.8–21.4), with a median PFS of 5.6 months (95% CI 3.7–6.3) and a median OS of 10.6 months (95% CI 8.9–14.9) [70].

6. nrgoncology.org nrgoncology.org/Clinical-Trials/Protocol/nrg-gy026?filter=nrg-gy026

NRG-GY026 A Phase II/III Study Of Paclitaxel/Carboplatin Alone Or Combined With Either Trastuzumab And Hyaluronidase-Oysk (Herceptin Hylecta) Or Pertuzumab, Trastuzumab, ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS5641

Phase II/III study of paclitaxel/carboplatin alone or ... Phase II data demonstrated a benefit in adding trastuzumab in HER2 positive advanced and recurrent uterine serous carcinoma. Dual anti-HER2 ...

8. aetna.com aetna.com/cpb/medical/data/300_399/0313.html

Trastuzumab (Herceptin and biosimilars) ... ... trastuzumab, carboplatin and paclitaxel is similar to historical data using carboplatin and paclitaxel alone. The investigators reported, however, that ...

9. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2019/761106Orig1s000MultidisciplineR.pdf

Multi-Discipline Review - accessdata.fda.gov HERCEPTIN HYLECTA is indicated for adjuvant treatment of adults with HER2 overexpressing node positive or node negative (ER/PR negative or with one high risk ...