Chemo-Radiation for Early-Stage Cervical Cancer

No longer recruiting at 135 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: Radiation Therapy Oncology Group

Disqualifiers: Neuroendocrine histology, Distant metastases, Others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 12

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of combining chemotherapy and radiation therapy, focusing on whether additional chemotherapy improves treatment for early-stage cervical cancer. Participants will receive either standard chemotherapy (including drugs like Carboplatin and Cisplatin) and radiation therapy or an extra round of chemotherapy after initial treatment. This study targets individuals who recently underwent surgery for high-risk, early-stage cervical cancer and may have high-risk features, such as positive pelvic or para-aortic nodes, where cancer cells may spread. It suits those who have had a radical hysterectomy within the past 70 days and seek post-surgery treatment options. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, you cannot have had prior systemic chemotherapy for cervical cancer or prior pelvic radiotherapy that overlaps with the trial's treatment areas.

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

Research has shown that cisplatin, a chemotherapy drug, is generally safe for treating early-stage cervical cancer. Studies have found it can cause side effects like nausea and kidney problems, but these are usually manageable. Serious side effects might occur, but they are less common.

When combined with carboplatin and paclitaxel, the safety profile remains similar. One study found that this combination can cause side effects like low blood cell counts and tiredness, but these are usually temporary and treatable.

Overall, these treatments have been used in cancer care for a long time, providing extensive safety information. However, individual reactions vary, so discussing specific risks with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for early-stage cervical cancer because they combine standard chemoradiotherapy with additional chemotherapy agents, which could enhance effectiveness. Arm I uses cisplatin with radiation, which is a traditional approach, but Arm II adds carboplatin and paclitaxel after radiation. This combination could potentially improve outcomes by targeting the cancer cells more aggressively. The addition of carboplatin and paclitaxel might help prevent disease progression more effectively than just using cisplatin and radiation alone.

What evidence suggests that this trial's treatments could be effective for early-stage cervical cancer?

Studies have shown that using cisplatin with radiation therapy, which participants in this trial may receive, effectively treats cervical cancer. This combination helps patients live longer and prevents the cancer from worsening. Another group of participants in this trial will receive additional treatment with carboplatin and paclitaxel following the cisplatin and radiation therapy. Research suggests that adding these two drugs might also be effective, as they work together to kill cancer cells and inhibit their growth. Early results indicate this approach is safe and could be a strong treatment option. Both treatment combinations in this trial show promise in fighting cervical cancer. ^{3 6 7 8 9}

Who Is on the Research Team?

Anuja Jhingran, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with high-risk early-stage cervical cancer who've had a radical hysterectomy. Eligible participants must have certain types of cervical cancer, no distant metastases, and their major organs functioning well. They should not have received prior chemotherapy or pelvic radiotherapy for the current cancer and must not have severe active co-morbidities.

Inclusion Criteria

Hemoglobin ≥ 10.0 g/dL

Serum creatinine ≤ 1.5 mg/dL

My cancer does not have neuroendocrine features.

Exclusion Criteria

I do not have a severe lung condition that would stop me from joining the study.

I have had previous radiation treatment to my pelvis.

I have not been hospitalized for heart issues in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemoradiotherapy

Patients undergo standard EBRT or IMRT to the pelvis once daily 5 days a week for 5-6 weeks with concurrent cisplatin IV once weekly for 6 weeks.

5-6 weeks

5 visits per week (in-person)

Adjuvant Chemotherapy

Patients receive paclitaxel and carboplatin IV every 21 days for 4 cycles, starting 4-6 weeks after chemoradiotherapy.

12 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

5 years

Every 3 months for 2 years, every 6 months for 3 years, then annually

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Cisplatin
• Paclitaxel
• Pelvic Radiation Therapy

Trial Overview

The study is testing how effective chemotherapy (cisplatin, paclitaxel, carboplatin) combined with pelvic radiation therapy is compared to the same treatment plus additional chemotherapy in treating high-risk early-stage cervical cancer post-surgery.

How Is the Trial Designed?

Group I: Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel Experimental Treatment 6 Interventions

Chemoradiotherapy as in arm I, followed 4-6 weeks later by paclitaxel IV \[135 mg/m2, with maximum body surface area (BSA) of 2.0 m\^2 over 3 hours\] and carboplatin IV \[area under the curve (AUC) 5 over 30 minutes\] on day 1 of 21-day cycle for 4 cycles in the absence of disease progression or unacceptable toxicity.

Group II: Arm I: Cisplatin/Radiation Therapy Active Control 4 Interventions

Standard external beam radiation therapy (EBRT) or intensity-modulated radiation therapy (IMRT) to the pelvis once daily 5 days a week for 5-6 weeks as 45 Gy in 25 fractions or 50.4 Gy in 28 fractions (1.8 Gy/fraction). Concurrent cisplatin IV over one hour once weekly for 6 weeks as 40 mg/m\^2, maximum dose 70 mg. A brachytherapy boost following radiation therapy is optional.

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?

Radiation Therapy Oncology Group

Lead Sponsor

Trials

191

Recruited

64,900+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

NRG Oncology

Collaborator

Trials

242

Recruited

105,000+

Published Research Related to This Trial

The maximum-tolerated dose (MTD) of paclitaxel when combined with cisplatin and pelvic radiotherapy for cervical cancer patients was determined to be 50 mg/m2 per week, with diarrhea identified as the main dose-limiting toxicity.

In a study of 18 patients, the combination treatment resulted in a high overall response rate of 92.3%, with 7 complete and 5 partial responses, indicating that this regimen could be an effective option for treating locally advanced cervical cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study with weekly cisplatin-paclitaxel and concurrent radiotherapy in patients with carcinoma of the cervix uteri. Pignata, S., Frezza, P., Tramontana, S., et al.[2020]

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 I trial involving 21 patients with locally advanced cervical cancer, the maximum tolerated dose (MTD) of weekly paclitaxel in combination with cisplatin was determined to be 40 mg/m², indicating a safe dosage for further studies.

The combination of weekly paclitaxel and cisplatin alongside radiation therapy was feasible and showed an acceptable toxicity profile, with significant side effects like grade 3 proctitis and vaginitis occurring at higher doses of paclitaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maximum tolerated dose and early response - results of a phase I trial of paclitaxel and cisplatin with radiation therapy in carcinoma of the cervix. Prasad, E., Viswanathan, PN., Rangad, VF., et al.[2015]

The combination of weekly paclitaxel and cisplatin during radiation therapy shows promising efficacy in 'high-risk' cervical cancer patients, with an overall survival rate of 68% at a median follow-up of 58 months.

While hematologic toxicity was common, it was manageable and did not frequently cause treatment delays; however, significant late complications occurred in 52% of patients, indicating the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation therapy with concomitant and adjuvant cisplatin and paclitaxel in high-risk cervical cancer: long-term follow-up. Argenta, PA., Ghebre, R., Dusenbery, KE., et al.[2020]

In a study of 271 patients with high-risk cervical cancer, sequential treatment with paclitaxel and carboplatin followed by radiation showed a 5-year survival rate of 85.8%, compared to 78.9% for simultaneous cisplatin-based radiochemotherapy, although the difference was not statistically significant (P = 0.25).

The sequential treatment resulted in lower rates of severe hematological toxicity and early treatment termination compared to the simultaneous approach, suggesting it may be a safer alternative when immediate postoperative radiation is not feasible.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized phase III adjuvant study in high-risk cervical cancer: simultaneous radiochemotherapy with cisplatin (S-RC) versus systemic paclitaxel and carboplatin followed by percutaneous radiation (PC-R): a NOGGO-AGO Intergroup Study. Sehouli, J., Runnebaum, IB., Fotopoulou, C., et al.[2023]

The study established that the maximum tolerated dose (MTD) for carboplatin in combination with weekly paclitaxel is AUC 2.5, indicating a safe dosage for further testing in phase II trials.

Weekly chemoradiotherapy with paclitaxel and carboplatin is feasible and shows promising efficacy, with a 2-year progression-free survival (PFS) rate of 80% and overall survival (OS) rate of 86% in patients with locally advanced cervical cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I clinical trial of weekly paclitaxel, weekly carboplatin, and concurrent radiotherapy for primary cervical cancer. Rao, GG., Rogers, P., Drake, RD., et al.[2015]

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Cisplatin (intravenous route) - Side effects & uses

Cisplatin is an antineoplastic agent (cancer medicine). It interferes with the growth of cancer cells, which are eventually destroyed by the body.