Chemotherapy + Fertility-Sparing Surgery for Cervical Cancer

(CoNteSSa Trial)

Recruiting at 3 trial locations

Overseen By Stephanie Lheureux

Age: 18 - 65

Sex: Female

Trial Phase: Academic

Sponsor: University Health Network, Toronto

Must not be taking: Investigational agents

Disqualifiers: Other cancers, Brain metastases, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: 4

90 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will include patients with invasive cervical cancer that wish to keep their fertility as much as possible in the future after treatment. Patients who receive surgery alone may experience long-term side effects including infertility. The purpose of this research study is to determine whether giving neo-adjuvant chemotherapy prior to surgery can maintain fertility in patients with invasive cervical cancer. The neo-adjuvant chemotherapy will consist of a platinum-based chemotherapy drug cisplatin or carboplatin, with a chemotherapy drug called paclitaxel. These are common chemotherapy drugs used in the treatment of women with cervical cancers.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on investigational agents or treatments for other cancers, you may not be eligible to participate.

What data supports the effectiveness of the chemotherapy drugs used in the trial for cervical cancer?

Research shows that the combination of paclitaxel and carboplatin or cisplatin is effective in treating advanced or recurrent cervical cancer, with studies indicating it can help manage the disease, although it may have significant side effects. ^{1 2 3 4 5}

Is the combination of chemotherapy drugs like paclitaxel and carboplatin or cisplatin safe for treating cervical cancer?

Research shows that the combination of paclitaxel with either carboplatin or cisplatin is generally safe for treating cervical cancer, though it can cause side effects like gastrointestinal issues and bone marrow suppression. Carboplatin is noted to have milder kidney-related side effects compared to cisplatin, making it a potentially safer option. ^{1 4 5 6 7}

What makes the chemotherapy and fertility-sparing surgery treatment for cervical cancer unique?

This treatment combines chemotherapy with fertility-sparing surgery, which is different from standard treatments that often involve more aggressive surgery or radiation that can affect fertility. The use of carboplatin, cisplatin, and paclitaxel in this context aims to treat the cancer while preserving the patient's ability to have children. ^{2 3 5 7 8}

Research Team

Stephanie Lheureux

Principal Investigator

Princess Margaret Cancer Centre

Eligibility Criteria

This trial is for premenopausal women with FIGO 2018 Stage IB2 cervical cancer who wish to preserve fertility and haven't had prior cancer treatments. They should have a good performance status, no uncontrolled infections, measurable disease per RECIST 1.1, and normal organ/marrow function. Participants must agree to use contraception.

Inclusion Criteria

I am premenopausal and want to keep my ability to have children.

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

My organ and bone marrow functions are normal.

Exclusion Criteria

My cancer has grown or remained larger than 2cm despite chemotherapy.

I couldn't complete 3 cycles of initial cancer treatment before surgery.

You have had allergic reactions to medications that are similar to paclitaxel, carboplatin, or cisplatin, or other drugs being used in the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neo-Adjuvant Chemotherapy

Participants receive platinum-based chemotherapy (cisplatin or carboplatin) with paclitaxel for three 21-day cycles

9 weeks

3 visits (in-person, one per cycle)

Surgery

Participants undergo trachelectomy if responding to treatment; otherwise, adjuvant treatment or hysterectomy may be performed

1-2 weeks

1 visit (in-person)

Adjuvant Treatment

Participants may receive additional chemotherapy and radiotherapy or undergo a hysterectomy based on post-surgery assessment

Varies

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

• Carboplatin
• Cisplatin
• Paclitaxel
• Trachelectomy

Trial Overview The study tests if neoadjuvant chemotherapy (cisplatin or carboplatin plus paclitaxel) before fertility-sparing surgery can maintain fertility in patients with invasive cervical cancer. It aims to see if this approach reduces long-term infertility risks compared to surgery alone.

Participant Groups

Group I: Neo-Adjuvant Chemotherapy, Surgery, and Adjuvant Chemotherapy Experimental Treatment 4 Interventions

Participants will receive neo-adjuvant treatment cisplatin or carboplatin with paclitaxel, intravenously, either once every cycle or once a week, for three (21-day) cycles. After neo-adjuvant treatment, depending on their status, participants may have the trachelectomy done. Adjuvant treatment may include standard chemotherapy and radiotherapy, or a hysterectomy may need to be done.

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+

Hotel Dieu Hospital

Collaborator

Trials

21

Recruited

20,000+

The Netherlands Cancer Institute

Collaborator

Trials

308

Recruited

216,000+

Findings from Research

In a multicenter phase II trial involving 68 patients with locally advanced cervical cancer, concurrent chemoradiotherapy (CCRT) using weekly cisplatin and paclitaxel resulted in a high complete response rate of 76.5%.

The treatment demonstrated favorable long-term outcomes, with 2-year progression-free survival at 83.8% and overall survival at 92.7%, while maintaining manageable safety profiles with a 25% rate of late complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of concurrent chemoradiotherapy with weekly cisplatin and paclitaxel in patients with locally advanced uterine cervical cancer: The JACCRO GY-01 trial. Umayahara, K., Takekuma, M., Hirashima, Y., et al.[2016]

In a phase II study involving 31 women with early-stage cervical cancer, the combination of carboplatin and paclitaxel as postoperative concurrent chemoradiotherapy (CCRT) followed by consolidation chemotherapy was well tolerated, with 83.9% of patients completing the treatment.

The treatment resulted in high efficacy, with 3-year progression-free survival (PFS) at 88.5% and overall survival (OS) at 93.8%, significantly outperforming historical controls that used single platinum agents or extended-field radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of postoperative concurrent carboplatin and paclitaxel combined with intensity-modulated pelvic radiotherapy followed by consolidation chemotherapy in surgically treated cervical cancer patients with positive pelvic lymph nodes. Mabuchi, S., Isohashi, F., Yokoi, T., et al.[2017]

Carboplatin-paclitaxel is an effective treatment for advanced or recurrent cervical cancer, showing a 20% partial response and 20% complete response rate in a study of 25 women, with a median overall survival of 21 months.

The treatment was well tolerated, with 84% of doses delivered on time and 96% at full dose, although common toxicities included anemia and neutropenia, highlighting the need for monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin and paclitaxel for advanced and recurrent cervical carcinoma: the British Columbia Cancer Agency experience. Tinker, AV., Bhagat, K., Swenerton, KD., et al.[2022]

In a study of 15 patients with recurrent or persistent cervical carcinoma, the combination of paclitaxel and carboplatin (PC) showed a 60% overall clinical response rate, with 27% achieving a complete response and 33% a partial response.

The median survival for patients treated with PC was 17 months, and the treatment had an acceptable toxicity profile, with significant side effects like neutropenia and neuropathy occurring in a minority of patients, suggesting that carboplatin may be a safer alternative to cisplatin in this regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel and carboplatin for recurrent or persistent cancer of the cervix. Sit, AS., Kelley, JL., Gallion, HH., et al.[2019]

In a study of 70 patients with locally advanced cervical cancer, neoadjuvant chemotherapy using paclitaxel and carboplatin or cisplatin resulted in a high overall response rate of 72.9%, with 20% achieving a complete response and 52.9% showing a partial response.

The treatment improved surgical resection rates, with 95.7% of patients undergoing surgery, and demonstrated tolerable side effects, making it a promising option for patients in the neoadjuvant setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Neoadjuvant chemotherapy with paclitaxel and cisplantin or carboplatin for patients with locally advanced uterine cervical cancer]. Zhang, R., Li, B., Bai, P., et al.[2015]

In a study of 116 patients with advanced or recurrent cervical cancer, the combination of paclitaxel and carboplatin (TC) showed similar overall survival and disease-control rates compared to paclitaxel and cisplatin (TP), indicating comparable efficacy.

The TC regimen was associated with significantly lower rates of severe gastrointestinal toxicity and shorter hospital stays, suggesting that TC may be a safer and more tolerable alternative to TP for treating this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective analysis of cisplatin/carboplatin plus paclitaxel in advanced or recurrent cervical cancer. Song, D., Kong, W., Zhang, T., et al.[2019]

In a study involving 635 patients with locally advanced squamous cervical cancer, cisplatin-based chemoradiation showed a superior 5-year disease-free survival (DFS) rate of 76.7% compared to 69.3% for neoadjuvant chemotherapy followed by surgery.

Patients receiving neoadjuvant chemotherapy experienced fewer delayed toxicities, particularly in bladder and vaginal areas, suggesting a potential safety advantage despite the lower DFS compared to chemoradiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant Chemotherapy Followed by Radical Surgery Versus Concomitant Chemotherapy and Radiotherapy in Patients With Stage IB2, IIA, or IIB Squamous Cervical Cancer: A Randomized Controlled Trial. Gupta, S., Maheshwari, A., Parab, P., et al.[2022]

In a study of 38 patients with locally advanced cervical cancer, a neoadjuvant chemotherapy regimen combining cisplatin, ifosfamide, and paclitaxel resulted in an overall response rate of 84%, with 34% achieving complete or optimal partial responses after treatment.

The treatment was associated with manageable side effects, including significant neutropenia in 71% of patients, indicating that while the regimen is effective, careful monitoring for toxicity is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant chemotherapy with cisplatin, ifosfamide and paclitaxel for locally advanced squamous-cell cervical cancer. Zanetta, G., Lissoni, A., Pellegrino, A., et al.[2020]

References

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

Phase II study of concurrent chemoradiotherapy with weekly cisplatin and paclitaxel in patients with locally advanced uterine cervical cancer: The JACCRO GY-01 trial. [2016]

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

A phase II study of postoperative concurrent carboplatin and paclitaxel combined with intensity-modulated pelvic radiotherapy followed by consolidation chemotherapy in surgically treated cervical cancer patients with positive pelvic lymph nodes. [2017]

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

Carboplatin and paclitaxel for advanced and recurrent cervical carcinoma: the British Columbia Cancer Agency experience. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Paclitaxel and carboplatin for recurrent or persistent cancer of the cervix. [2019]

5. China pubmed.ncbi.nlm.nih.gov

[Neoadjuvant chemotherapy with paclitaxel and cisplantin or carboplatin for patients with locally advanced uterine cervical cancer]. [2015]

6. England pubmed.ncbi.nlm.nih.gov

A retrospective analysis of cisplatin/carboplatin plus paclitaxel in advanced or recurrent cervical cancer. [2019]

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

Neoadjuvant Chemotherapy Followed by Radical Surgery Versus Concomitant Chemotherapy and Radiotherapy in Patients With Stage IB2, IIA, or IIB Squamous Cervical Cancer: A Randomized Controlled Trial. [2022]

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

Neoadjuvant chemotherapy with cisplatin, ifosfamide and paclitaxel for locally advanced squamous-cell cervical cancer. [2020]