Herceptin Hylecta or Phesgo + Chemotherapy for Uterine Cancer

Recruiting at 402 trial locations

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP2C8, CYP3A4

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

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of 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.

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.

What data supports the effectiveness of the drug combination Herceptin Hylecta or Phesgo with chemotherapy for uterine cancer?

Research shows that adding trastuzumab (a component of Herceptin Hylecta or Phesgo) to carboplatin and paclitaxel significantly increased the time patients with advanced or recurrent uterine serous carcinoma lived without their cancer getting worse, compared to using carboplatin and paclitaxel alone. ^{1 2 3 4 5}

Is the combination of Herceptin Hylecta or Phesgo with chemotherapy safe for treating uterine cancer?

The combination of paclitaxel and carboplatin, which are part of the chemotherapy regimen, has been studied for safety in treating endometrial cancer. These studies found that while the treatment is active against tumors, it can cause significant side effects like hematologic toxicity (blood-related side effects) and neuropathy (nerve damage). There was also one possible treatment-related death reported, indicating that while generally manageable, the treatment does carry some risks. ^{1 3 4 5 6}

What makes the drug combination of Herceptin Hylecta or Phesgo with chemotherapy unique for uterine cancer?

This treatment is unique because it combines targeted therapies (Herceptin Hylecta or Phesgo) with chemotherapy drugs (Carboplatin and Paclitaxel), which are known to be effective in other cancers, but not yet standard for uterine cancer. The inclusion of targeted therapies like Pertuzumab and Trastuzumab, which specifically target cancer cell growth, offers a novel approach compared to traditional chemotherapy alone. ^{1 3 4 7 8}

Research Team

Britt K Erickson

Principal Investigator

NRG Oncology

Eligibility Criteria

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.

Trial Timeline

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)

Treatment Details

Interventions

• Carboplatin (Chemotherapy)
• Paclitaxel (Chemotherapy)
• Pertuzumab (Monoclonal Antibodies)
• Trastuzumab (Monoclonal Antibodies)

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.

Participant Groups

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

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 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 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. 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 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. 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 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 Canada for the following indications:

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+

Findings from Research

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 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]

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 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]

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]

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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Paclitaxel, topotecan, and carboplatin in metastatic endometrial cancinoma: a Hellenic Co-operative Oncology Group (HeCOG) study. [2015]

2. United States 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. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

A trial of outpatient paclitaxel and carboplatin for advanced, recurrent, and histologic high-risk endometrial carcinoma: preliminary report. [2016]

4. Germany pubmed.ncbi.nlm.nih.gov

Tislelizumab Combined with Carboplatin-Paclitaxel for Treatment of Metastatic or Recurrent Endometrial Cancer: a Retrospective Clinical Study. [2022]

5. United States 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. [2015]

6. United States pubmed.ncbi.nlm.nih.gov

Carboplatin and paclitaxel for the treatment of advanced or recurrent endometrial cancer. [2015]

7. Germany 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. [2015]

8. England pubmed.ncbi.nlm.nih.gov

A pilot study of topotecan in the treatment of serous carcinoma of the uterus. [2019]