Chemotherapy + Fertility-Sparing Surgery for Cervical Cancer

(CoNteSSa Trial)

Recruiting at 2 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

31 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining chemotherapy with surgery can help preserve fertility in women with invasive cervical cancer. The treatment uses common chemotherapy drugs, such as cisplatin or carboplatin, along with paclitaxel, to shrink the tumor before surgery. Researchers aim to determine if this approach can maintain fertility more effectively than surgery alone, which often results in infertility. The trial seeks women who are premenopausal, have not received prior treatment, and wish to preserve their fertility. As an unphased trial, it offers a unique opportunity for women to contribute to research that could lead to fertility-preserving treatments.

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.

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

Research has shown that the combination of chemotherapy drugs cisplatin, carboplatin, and paclitaxel is generally well-tolerated by patients with cervical cancer. Studies have found that this drug combination can effectively treat advanced cervical cancer, with 40-50% of patients responding well. Additionally, when combined with radiation, carboplatin and paclitaxel tend to cause fewer side effects, making them a safer choice for many patients.

Regarding surgery, trachelectomy, a fertility-preserving procedure, has been found to be safe for patients. One study showed that the risk of cancer recurrence after trachelectomy was only about 3%. While some risks, such as miscarriage, exist, the surgery has shown promising results in preserving fertility and maintaining good cancer outcomes.

Overall, existing research suggests that the chemotherapy and surgical options in this study are both safe and effective, with manageable side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for cervical cancer because it combines chemotherapy with fertility-sparing surgery, offering a unique approach for patients who wish to preserve fertility. Unlike standard treatments that often involve a hysterectomy, this approach allows for the potential of keeping the uterus intact by using a trachelectomy. The chemotherapy regimen includes carboplatin, cisplatin, and paclitaxel, which are well-known for their effectiveness in reducing tumor size before surgery, potentially improving surgical outcomes and preserving fertility options.

What evidence suggests that this trial's treatments could be effective for maintaining fertility in cervical cancer patients?

In this trial, participants will receive a combination of cisplatin or carboplatin with paclitaxel as part of the neo-adjuvant chemotherapy regimen. Research has shown that using cisplatin or carboplatin with paclitaxel is a promising approach for treating cervical cancer. Studies have found that treatments based on cisplatin effectively manage cervical cancer and result in good survival rates. Although carboplatin is slightly less effective than cisplatin, it still performs well. Adding paclitaxel enhances the treatment's overall effectiveness.

For patients wishing to maintain their ability to have children, this trial includes the option of a radical trachelectomy. This procedure has shown promise, offering similar cancer-fighting results to more invasive surgeries like a hysterectomy but without removing reproductive organs. The combination of chemotherapy and surgery in this trial aims to treat cancer while preserving fertility. ^{4 6 7 8 9}

Who Is on the Research Team?

Stephanie Lheureux

Principal Investigator

Princess Margaret Cancer Centre

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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 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 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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/24486604/

A systematic review comparing cisplatin and carboplatin ... Introduction: The prognosis of advanced/recurrent cervical cancer patients is generally poor with 1-year survival ranging between 15 and 20%. Cisplatin (CDDP) ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2014.58.4391

The Open-Label Randomized Phase III Trial JCOG0505 Carboplatin has been reported to be a less effective platinum analog than cisplatin for cervical cancer,7–9 but these agents have not been ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S102845592400278X

The real-world efficacy and toxicity of first-line paclitaxel ... Nonetheless, along with these results, we demonstrated that paclitaxel-cisplatin-bevacizumab was effective for platinum-naïve primary stage IVB cervical cancer.

4. sgo.org sgo.org/news/drugshortages2/

SGO, FWC, and GOG-F* Communique Cisplatin and carboplatin should be reserved for cervical cancer treatment with curative intent, namely for those patients receiving concomitant ...

5. ejgo.net ejgo.net/articles/10.22514/ejgo.2023.109

Comparison of the clinical efficacy of paclitaxel + ... We conclude that the combination of paclitaxel and carboplatin was an effective treatment approach for cervical cancer patients, offering comparative advantages ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12227970/

Phase II Study to Evaluate the Safety and Efficacy ... Platinum and taxane together have been shown to be effective in treating advanced and recurrent cervical cancer, with 40–50% overall response rates [12]. A ...

7. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(24)01438-7/fulltext

an international, multicentre, randomised phase 3 trial The results of INTERLACE show that a short course of chemotherapy using 6 weeks of carboplatin and paclitaxel immediately before standard ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S1048891X2418838X

Efficacy And Safety Of Concurrent Chemoradiotherapy ... Conclusions Paclitaxel-carboplatin is an active combination with radiation in advanced cervical cancer. This combination has less toxic side effects, especially ...

9. asco.org asco.org/abstracts-presentations/ABSTRACT171304

Analysis of safety and outcome of the combination ... Cisplatin and C in combination with P are equally effective in terms of OS however CP seems to be better tolerated (Kiagawa R, et al; J Clin Oncol Jul 1, 2015: ...