Triapine + Chemotherapy/Radiation for Cervical and Vaginal Cancers

Not currently recruiting at 422 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding the drug triapine to the standard treatment of radiation and chemotherapy (cisplatin) improves outcomes for patients with certain types of cervical and vaginal cancer. The researchers aim to determine if this combination more effectively stops tumor growth than the current standard treatment. Patients recently diagnosed with stage IB2, II, or IIIB-IVA cervical cancer, or stage II-IVA vaginal cancer, who have not had surgery as a treatment option, might find this trial suitable. 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 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.

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

Earlier research has shown that triapine, when combined with cisplatin and radiation, is well-tolerated by patients with cervical and vaginal cancers. One study found that adding triapine to cisplatin and radiation treatment was manageable and led to positive outcomes in women with these cancers. This suggests that triapine can be safely included with traditional treatments like cisplatin and radiation without causing severe side effects. Although researchers continue to study triapine, these findings provide promising evidence of its safety when used with other cancer treatments. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the combination of triapine with chemotherapy and radiation for cervical and vaginal cancers because it introduces a unique approach to treatment. Unlike the standard cisplatin-based chemoradiation, this treatment adds triapine, which targets a different pathway by inhibiting ribonucleotide reductase, an enzyme critical for DNA synthesis in cancer cells. This dual-action approach not only aims to enhance the effectiveness of existing treatments but also potentially reduces the likelihood of cancer cells developing resistance. By incorporating triapine, there's hope for more efficient eradication of cancer cells, potentially improving patient outcomes.

What evidence suggests that this trial's treatments could be effective for cervical and vaginal cancers?

This trial will compare two treatment approaches for cervical and vaginal cancers. In one arm, participants will receive cisplatin with radiation therapy and brachytherapy. In the other arm, participants will receive the same regimen with the addition of triapine. Research has shown that triapine, when combined with cisplatin and radiation therapy, may aid in treating these cancers. Studies have found that triapine can enhance the effectiveness of other cancer treatments by inhibiting enzymes necessary for cancer cell growth. In one study, patients who received triapine with cisplatin and radiation had an 83% survival rate after 30 months. However, another study found that adding triapine did not significantly improve results compared to standard treatments. This mixed evidence suggests potential benefits, but more research is needed to confirm its effectiveness. ^{1 3 5 6 7}

Who Is on the Research Team?

Charles A Leath

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

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.

Patient is receiving another investigational agent for the treatment of cancer

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4260802/

Radiochemotherapy plus 3-aminopyridine-2 ... The addition of 3-AP to cisplatin radiochemotherapy was tolerable and produced high rates of clinical and metabolic responses in women with cervical and vaginal ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0006295299004190

Triapine (3-aminopyridine-2-carboxaldehyde ... The findings demonstrate the superiority of Triapine over hydroxyurea as an anticancer agent and further suggest that prevention by Triapine of repair of DNA ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5949312/

Triapine Radiochemotherapy in Advanced Stage Cervical ... Overall survival estimates after triapine–cisplatin–radiation treatment was 83% (95% CI, 63–92%) at 30 months and 59% (95% CI, 39–74%) at 60 ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0090825825000769

Results from NRG-GY006, a phase III randomized trial The addition of triapine to chemoradiation did not improve outcomes. IMRT was utilized and was able to undergo near real time QA to allow treatment plan ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02595879

Triapine With Chemotherapy and Radiation Therapy in ... Triapine may stop the growth of cancer cells by blocking an enzyme needed for cell growth. Cisplatin is a drug used in chemotherapy that kills cancer cells by ...

6. asco.org asco.org/abstracts-presentations/ABSTRACT74945

Phase II trial of pelvic radiation, weekly cisplatin, and 3- ... Background: This on-going clinical trial assesses the safety and clinical activity of 3x weekly intravenous 3-aminopyridine-2-carboxaldehyde ...

7. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2019.01067/full

Randomized Phase II Trial of Triapine-Cisplatin ... For the intention-to-treat groups, the rate of clinical complete response was 92% (12 of 13 patients) in the triapine group and 62% (8 of 13 ...