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

267 Participants Needed

Trial Summary

What is the purpose of this trial?

This is an umbrella, two-arm, multi-stage, phase II trial. The purpose of the trial in the early stage cohort is to determine if EBRT improves disease free survival (defined as the time from random assignment to disease recurrence or death from any cause) compared to vaginal brachytherapy after chemotherapy in women with serous or p53 aberrant endometrial cancer. The purpose of the trial in the advanced stage cohort is to determine if the maintenance with experimental treatment increases progression free survival, defined as the time from random assignment to disease progression or death from any cause.

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.

What data supports the effectiveness of the drug combination of carboplatin and paclitaxel for endometrial cancer?

Research shows that the combination of carboplatin and paclitaxel is effective in treating advanced or recurrent endometrial cancer, with a response rate of 67% and a complete response rate of 29%. However, the treatment can cause side effects like blood-related issues and nerve damage. ^{1 2 3 4 5}

Is the combination of carboplatin and paclitaxel generally safe for humans?

The combination of carboplatin and paclitaxel has been studied for endometrial cancer and is generally considered to have acceptable levels of toxicity, though some patients experienced severe side effects like grade 3 or 4 hematologic toxicity (blood-related side effects) and neuropathy (nerve damage). There was one possible treatment-related death reported, indicating that while generally safe, there are risks involved. ^{1 3 4 5 6}

How is the drug combination of Carboplatin, Cisplatin, Niraparib, and Paclitaxel unique for treating endometrial cancer?

This drug combination is unique because it includes both platinum compounds (Carboplatin and Cisplatin) and a taxane (Paclitaxel), which have shown improved response rates and survival in endometrial cancer. The addition of Niraparib, a PARP inhibitor, may offer further benefits, although its specific role in this combination for endometrial cancer is not well-established. ^{4 6 7 8 9}

Research Team

Amit Oza, MD

Principal Investigator

Princess Margaret Cancer Centre

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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 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 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]

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]

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]

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]

References

1. 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]

2. England pubmed.ncbi.nlm.nih.gov

Treatment of primary advanced and recurrent endometrial carcinoma with a combination of carboplatin and paclitaxel-long-term follow-up. [2018]

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

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

4. United States 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). [2015]

5. United States 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. [2023]

6. 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]

7. Australia pubmed.ncbi.nlm.nih.gov

Paclitaxel/carboplatin versus cyclophosphamide/adriamycin/cisplatin as postoperative adjuvant chemotherapy for advanced endometrial adenocarcinoma. [2015]

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

Prolonged remission of endometrial cancer with paclitaxel and carboplatin. [2019]

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

Chemotherapy in endometrial cancer. [2007]