Various Treatments for Endometrial Cancer

(CAN-STAMP Trial)

Overseen By Amit Oza, MD

Age: 18+

Sex: Female

Trial Phase: Phase 2 & 3

Sponsor: University Health Network, Toronto

Must not be taking: Investigational agents, Antiretrovirals

Disqualifiers: Mixed serous tumors, Carcinosarcoma, Brain metastases, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 5 weeks for EBRT, 3 fractions for brachytherapy, daily for niraparib

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores treatments for endometrial cancer, specifically targeting women with serous types or p53 gene changes. For women in the early stages, the trial compares the effectiveness of two radiation therapies to determine which better prevents cancer recurrence. In advanced cases, it tests a new medication, Niraparib (a type of targeted therapy), to assess its ability to slow cancer progression. Women diagnosed with these specific cancer types who have undergone surgery might be suitable candidates for this trial. As a Phase 2 and Phase 3 trial, it measures treatment effectiveness in a smaller group and represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking advancements in cancer care.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are receiving other investigational agents or have been treated with certain types of radiotherapy recently.

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

Research has shown that treatments for endometrial cancer vary in safety levels.

For external beam radiation therapy (EBRT), studies have found it generally safe with a low risk of serious side effects. However, there is a small chance it could increase the risk of other cancers, such as non-Hodgkin lymphoma, over time.

Vaginal high-dose rate brachytherapy is well-tolerated, with patients experiencing few side effects both immediately and long-term, making it a reliable option for many.

Niraparib, also used for ovarian cancer, has been studied in large groups of women and found effective and safe. Most patients tolerate it well, especially when doses are adjusted to individual needs.

Overall, these treatments have been researched for safety and have shown positive results, making them promising options for those considering clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments in this trial for endometrial cancer because they explore different approaches compared to standard chemotherapy or radiation. Unlike traditional methods, Niraparib, an investigational agent, is a PARP inhibitor taken orally, which targets cancer cells more precisely based on their DNA repair weaknesses. The trial also compares different radiation techniques, like high-dose rate brachytherapy, which delivers radiation directly to the tumor site, potentially reducing side effects. Additionally, the trial studies the effects of pelvic external beam radiation therapy (EBRT) in early-stage treatment, offering a more targeted and possibly less invasive option. Together, these treatments could provide more personalized and effective care options for endometrial cancer patients.

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

This trial will evaluate various treatments for endometrial cancer. External beam radiation therapy (EBRT), which participants may receive, has been shown in studies to help women with high-intermediate risk endometrial cancer live longer. It effectively targets cancer cells in early-stage endometrial cancer using precise radiation. Another treatment option in this trial is the investigational drug niraparib. Research indicates that niraparib can significantly extend the time during which the cancer does not worsen for some patients. Specifically, studies suggest that for patients with certain genetic markers, niraparib can nearly halve the risk of cancer progression or death. These treatments show promise for improving outcomes in endometrial cancer. ^{2 3 6 7 8}

Who Is on the Research Team?

Amit Oza, MD

Principal Investigator

Princess Margaret Cancer Centre

Are You a Good Fit for This Trial?

This trial is for women with serous or p53 abnormal endometrial cancer who've had optimal surgery, have a performance status ≤2, and available tissue samples. They must understand the consent form, not have received prior treatment for this cancer, and agree to contraception. Exclusions include previous chemotherapy for endometrial cancer, certain mixed tumors, recent radiotherapy affecting bone marrow, uncontrolled illnesses that affect study compliance, known brain metastases unless stable post-treatment over 1 month, pregnancy, active HIV or Hepatitis B/C on therapy.

Inclusion Criteria

Ability to understand and willing to sign a written informed consent document.

Life expectancy of greater than 3 months.

My TP53 test results are ready for review.

Exclusion Criteria

I have brain complications from cancer but am stable without steroids or seizure meds for 7 days.

I do not have HIV, Hepatitis B, or C, or I am not on antiretroviral therapy.

History of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either pelvic EBRT or vaginal brachytherapy in the early stage cohort, or investigational agent niraparib in the advanced stage cohort

5 weeks for EBRT, 3 fractions for brachytherapy, daily for niraparib

Follow-up

Participants are monitored for disease recurrence or progression and overall survival

3-5 years

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Cisplatin
• External Beam Radiation
• Niraparib
• Paclitaxel

Trial Overview

The trial tests if external beam radiation (EBRT) improves disease-free survival compared to vaginal brachytherapy after chemotherapy in early-stage patients. For advanced stages, it examines whether maintenance with Niraparib increases progression-free survival. It's an umbrella two-arm phase II trial where participants are randomly assigned to treatments.

How Is the Trial Designed?

Group I: Early Stage Cohort - Arm B1 Experimental Treatment 2 Interventions

Vaginal high-dose rate brachytherapy 21 Gy in 3 fractions, prescribed to 5mm (i.e. 100% isodose at 5mm) from the cylinder/applicator surface and top along the upper third to half of the vagina (minimum 3cm, maximum 4cm).

Group II: Early Stage Cohort - Arm A Experimental Treatment 1 Intervention

Pelvic EBRT at 45Gy in 25 fractions, in 1.8Gy fractions daily, 5 days per week

Group III: Advanced Stage Cohort Arm D1 Experimental Treatment 1 Intervention

Investigational agent (niraparib), orally, at a dose of 200 mg, or 300 mg, once daily, based on baseline platelet count and weight.

Group IV: Advanced Stage Cohort Arm C Active Control 1 Intervention

Observation

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?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Published Research Related to This Trial

A patient with recurrent metastatic endometrial cancer achieved complete remission after 8 months of treatment with a combination of paclitaxel and carboplatin, which has lasted for 22 months.

This case suggests that the paclitaxel and carboplatin regimen could be a promising treatment option for patients with recurrent endometrial cancer, especially when other therapies have failed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged remission of endometrial cancer with paclitaxel and carboplatin. Vasuratna, A., Kudelka, AP., Edwards, CL., et al.[2019]

In a phase II study involving 66 patients with advanced and recurrent endometrial carcinoma, the combination of carboplatin and paclitaxel achieved an overall response rate of 67%, indicating a promising efficacy compared to previous treatments.

Despite the encouraging response rates, the median response duration was only 14 months, and the main toxicities included hematologic issues and sensory neuropathy, highlighting the need for further research to improve long-term outcomes and manage side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of primary advanced and recurrent endometrial carcinoma with a combination of carboplatin and paclitaxel-long-term follow-up. Sorbe, B., Andersson, H., Boman, K., et al.[2018]

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 28 patients with advanced endometrial adenocarcinoma, the paclitaxel/carboplatin regimen showed a higher response rate (77.8%) compared to the traditional CAP regimen (64.3%), indicating its effectiveness as a treatment option.

The paclitaxel/carboplatin group experienced significantly fewer severe toxicities, such as thrombocytopenia and gastrointestinal issues, compared to the CAP group, suggesting a better safety profile for the newer regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel/carboplatin versus cyclophosphamide/adriamycin/cisplatin as postoperative adjuvant chemotherapy for advanced endometrial adenocarcinoma. Hidaka, T., Nakamura, T., Shima, T., et al.[2015]

Endometrial cancer has a better prognosis when detected early, but for recurrent or metastatic cases, the median survival is only about 12 months, highlighting the need for effective treatment options.

Recent trials show that combining doxorubicin, cisplatin, and paclitaxel significantly improves response rates and overall survival compared to the standard doxorubicin plus cisplatin regimen, suggesting a more effective approach for treating advanced endometrial cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy in endometrial cancer. Obel, JC., Friberg, G., Fleming, GF.[2007]

The combination of triweekly carboplatin and weekly paclitaxel is feasible and effective for treating women with advanced or recurrent endometrial cancer, with 78% of patients completing at least 3 cycles of therapy.

Among patients with measurable disease, 87% showed a positive response to treatment, and quality of life scores significantly improved after 3 cycles, indicating both efficacy and a positive impact on patient well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A feasibility study of carboplatin and weekly paclitaxel combination chemotherapy in endometrial cancer: a Kansai Clinical Oncology Group study (KCOG0015 trial). Ito, K., Tsubamoto, H., Itani, Y., 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]

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 randomized phase II trial involving 349 patients with advanced endometrial cancer, the addition of novel agents to standard therapy (paclitaxel and carboplatin) did not significantly improve progression-free survival (PFS) compared to historical controls.

However, the combination of paclitaxel, carboplatin, and bevacizumab showed a significant increase in overall survival (OS) compared to controls, indicating that while PFS was not enhanced, the treatment may still offer long-term benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of frontline paclitaxel/carboplatin/bevacizumab, paclitaxel/carboplatin/temsirolimus, or ixabepilone/carboplatin/bevacizumab in advanced/recurrent endometrial cancer. Aghajanian, C., Filiaci, V., Dizon, DS., et al.[2023]

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