Triapine + Chemotherapy/Radiation for Cervical and Vaginal Cancers

Recruiting at 409 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: Antiretrovirals, Investigational agents

Disqualifiers: Active malignancy, Uncontrolled illness, Pregnancy, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 7 weeks

450 Participants Needed

Trial Summary

What is the purpose of this trial?

This randomized phase III trial studies radiation therapy and cisplatin with triapine to see how well they work compared to the standard radiation therapy and cisplatin alone in treating patients with newly diagnosed stage IB2, II, or IIIB-IVA cervical cancer or stage II-IVA vaginal cancer. Radiation therapy uses high energy protons to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Triapine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether radiation therapy and cisplatin are more effective with triapine in treating cervical or vaginal cancer.

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

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are HIV-positive and on antiretroviral therapy, you are not eligible to participate due to potential interactions with the trial drug, triapine.

What data supports the effectiveness of the drug combination Triapine and Cisplatin for treating cervical and vaginal cancers?

Cisplatin is a key drug in treating advanced cervical cancer, showing significant response rates when used alone or with radiation therapy. Studies have shown that combining cisplatin with radiation can improve survival in patients with advanced cervical cancer, suggesting its potential effectiveness in combination therapies. ^{1 2 3 4 5}

Is the combination of Triapine and Cisplatin with radiation therapy safe for treating cervical and vaginal cancers?

Studies have shown that combining Cisplatin with radiation therapy is generally safe for treating cervical cancer, with common side effects including nausea, vomiting, and anemia (low red blood cell count). The overall toxicity was considered acceptable, suggesting it is safe to use in larger studies. ^{5 6 7 8 9}

What makes the Triapine + Cisplatin treatment unique for cervical and vaginal cancers?

The Triapine + Cisplatin treatment is unique because it combines Triapine, which inhibits an enzyme crucial for DNA repair, with Cisplatin and radiation, enhancing the treatment's ability to damage cancer cells and improve outcomes without significant additional toxicity. ^{2 10 11 12 13}

Research Team

Charles A Leath

Principal Investigator

NRG Oncology

Eligibility Criteria

This trial is for patients with advanced-stage cervical or vaginal cancer, specifically stages IB2, II, or IIIB-IVA. Participants must have adequate organ function (e.g., hemoglobin >10 g/dL, creatinine ≤1.5 mg/dL), no severe allergies to triapine, not be breastfeeding, and cannot have HIV or other conditions that would interfere with the study drugs.

Inclusion Criteria

Patient is not actively breastfeeding (or has agreed to discontinue breastfeeding before the initiation of protocol therapy)

Absolute neutrophil count > 1,500/uL

Platelets > 100,000/uL

Exclusion Criteria

I have been diagnosed with G6PD deficiency.

I do not have any major health issues that are not under control.

Patient is receiving another investigational agent for the treatment of cancer

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cisplatin and radiation therapy, with or without triapine, over a period of approximately 7 weeks

7 weeks

Daily visits for radiation therapy, weekly visits for chemotherapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

1 and 3 months post-treatment, every 3 months for 2 years, then every 6 months for 3 years

Treatment Details

Interventions

• Cisplatin
• Triapine

Trial Overview The trial is testing if adding Triapine to standard chemotherapy (Cisplatin) and radiation therapy improves outcomes in treating advanced cervical and vaginal cancers. It's a phase III study where some patients will receive the usual treatment while others will get the new combination including Triapine.

Participant Groups

Group I: Arm II (cisplatin, IMRT or RT, brachytherapy, triapine) Experimental Treatment 6 Interventions

Patients receive cisplatin and undergo EBRT followed by brachytherapy as in Arm I. Patients also receive triapine IV over 2 hours on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33. Treatment continues in the absence of disease progression or unacceptable toxicity.

Group II: Arm I (cisplatin, IMRT or RT, brachytherapy) Active Control 6 Interventions

Patients receive cisplatin IV over 90 minutes on days 2, 9, 16, 23, 30, (and day 36 or 37 at the treating physician's discretion). Patients then undergo EBRT (either conventional RT or IMRT) QD 5 days a week for 25 fractions followed by LDR or HDR brachytherapy according to institution's standards. Treatment continues in the absence of disease progression or unacceptable toxicity.

Cisplatin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

NRG Oncology

Collaborator

Trials

242

Recruited

105,000+

Findings from Research

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]

A study involving 10 patients with advanced cervical cancer evaluated the safety of combining cisplatin with radiation therapy, finding that most adverse effects were mild (grade 2 or less), with nausea/vomiting being the most common issue.

Despite some cases of anemia being noted as a serious concern, the overall toxicity of the treatment was deemed acceptable, suggesting that larger studies can be conducted to further assess the efficacy of this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advanced cervical cancer therapy: concurrent radiation therapy and cisplatin chemotherapy for advanced cervical cancer--a toxicity report. Suggs, CL., Lee, JC., Lewis, GC., et al.[2013]

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 24 patients with advanced-stage cervical cancer, triapine combined with cisplatin and radiation therapy demonstrated a low 3-year pelvic locoregional relapse rate of 4%, indicating its potential effectiveness in treatment.

The treatment resulted in high disease-free survival (80%) and overall survival (82%) rates over a median follow-up of 3.4 years, suggesting that triapine is a safe and promising option for patients with untreated cervical cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Disease Control with Triapine-Based Radiochemotherapy for Patients with Stage IB2-IIIB Cervical Cancer. Kunos, CA., Sherertz, TM.[2021]

References

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

The role of cisplatin in the management of advanced squamous cell cancer of the cervix. [2013]

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

Propensity score matching analysis to comparing cisplatin versus nedaplatin based doublet agent concurrent chemoradiotherapy for locally advanced cervical cancer. [2023]

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

Phase III trial comparing radical radiotherapy with and without cisplatin chemotherapy in patients with advanced squamous cell cancer of the cervix. [2022]

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

Cisplatin in advanced cancer of the cervix: an update. [2013]

5. England pubmed.ncbi.nlm.nih.gov

Phase I study with weekly cisplatin-paclitaxel and concurrent radiotherapy in patients with carcinoma of the cervix uteri. [2020]

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

Advanced cervical cancer therapy: concurrent radiation therapy and cisplatin chemotherapy for advanced cervical cancer--a toxicity report. [2013]

7. Singapore pubmed.ncbi.nlm.nih.gov

Radiation therapy with concomitant and adjuvant cisplatin and paclitaxel in high-risk cervical cancer: long-term follow-up. [2020]

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

Potentiation of radiotherapy by cis-dichlorodiammine platinum (II) in advanced cervical carcinoma. [2019]

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

Long-term follow-up of a randomized trial comparing concurrent single agent cisplatin, cisplatin-based combination chemotherapy, or hydroxyurea during pelvic irradiation for locally advanced cervical cancer: a Gynecologic Oncology Group Study. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Long-Term Disease Control with Triapine-Based Radiochemotherapy for Patients with Stage IB2-IIIB Cervical Cancer. [2021]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Randomized Phase II Trial of Triapine-Cisplatin-Radiotherapy for Locally Advanced Stage Uterine Cervix or Vaginal Cancers. [2020]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Triapine Radiochemotherapy in Advanced Stage Cervical Cancer. [2020]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Phase I Trial of Triapine-Cisplatin-Paclitaxel Chemotherapy for Advanced Stage or Metastatic Solid Tumor Cancers. [2020]