Nelfinavir + Chemoradiation for Vulvar Cancer

Overseen By Lilie L Lin

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Anti-arrhythmics, Ergot derivatives, Sedatives, others

Disqualifiers: Metastases, Severe infection, Pregnancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the best dose and understand the side effects of adding nelfinavir, an antiviral drug, to a treatment plan that includes cisplatin (a chemotherapy drug) and radiation therapy for vulvar cancer. The focus is on patients whose cancer has spread to nearby tissues or lymph nodes and cannot be surgically removed. The study explores whether combining these treatments can be more effective than the standard approach. Ideal participants are those diagnosed with vulvar cancer that cannot be surgically removed and have not yet received treatment.

As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you cannot take certain drugs like anti-arrhythmics, ergot derivatives, and some sedatives during the trial. It's best to discuss your current medications with the trial team.

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

A previous study found that nelfinavir, a drug commonly used to treat HIV, improved the effectiveness of cancer treatments. When added to standard treatments like the chemotherapy drug cisplatin and radiation therapy, it made cancer cells more responsive. Cisplatin treats various cancers and is generally well-tolerated, though it can cause side effects like nausea and kidney problems. External beam radiation therapy (EBRT) uses high-energy rays to target cancer cells and has effectively treated vulvar cancer, though it may cause skin irritation and tiredness.

This trial is in its early stages and primarily aims to assess the safety of nelfinavir when combined with cisplatin and EBRT. Early phase trials often have limited safety data, but researchers will closely monitor any serious side effects. Since nelfinavir is already approved for other uses, this provides some reassurance about its safety. However, because it’s being used in a new way here, monitoring for any new side effects is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for vulvar cancer, which typically include surgery, radiation, and chemotherapy, this new approach incorporates nelfinavir, an HIV medication, into the mix. Nelfinavir is thought to enhance the effectiveness of radiation therapy by making cancer cells more sensitive to it. This combination aims to improve treatment outcomes by attacking the cancer from multiple angles, potentially offering better results than the current standard of care. Researchers are excited because this could mean more effective treatment options with possibly fewer side effects.

What evidence suggests that this trial's treatments could be effective for vulvar cancer?

Research has shown that nelfinavir can make cancer cells more responsive to chemotherapy and radiation. Although typically used to treat HIV, studies suggest nelfinavir might also help fight cancer. In this trial, participants will receive a combination of nelfinavir, cisplatin, and external beam radiation therapy. This combination aims to stop tumor growth and shrink tumors in vulvar cancer. While specific data on this combination for vulvar cancer is still being gathered, it appears promising based on nelfinavir's effectiveness in improving treatment for other cancers. ^{6 7 8 9 10}

Who Is on the Research Team?

Lilie L. Lin

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with locally advanced vulvar cancer that can't be surgically removed. Eligible participants have not had prior treatment, are in good enough health to undergo therapy (ECOG/GOG status 0-2), and have proper organ function. They must not be pregnant, HIV positive, or have other conditions like severe infections or diabetes that aren't well-managed.

Inclusion Criteria

Hematoxylin & eosin (H & E) stained slide showing documentation of the primary invasive cancer is required

Absolute neutrophil count (ANC) >= 1,500/microliter (performed within 28 days from signing consent form)

Platelet count >= 100,000/microliter (performed within 28 days from signing consent form)

Exclusion Criteria

I am pregnant and do not plan to terminate the pregnancy before starting treatment.

Patients who have circumstances that will not permit completion of this study or the required follow-up

My diabetes is not well-managed even with medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nelfinavir orally twice daily for up to 8 weeks. Starting week 2, they also receive cisplatin intravenously once weekly and undergo external beam radiation therapy for 5 consecutive days each week during weeks 2-8.

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment completion every 3-6 months for 1 year.

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• External Beam Radiation Therapy
• Nelfinavir

Trial Overview The study is testing the combination of nelfinavir (an antiviral drug), cisplatin (a chemotherapy drug), and external beam radiation therapy to see if they're more effective together than just cisplatin and radiation alone for treating vulvar cancer.

How Is the Trial Designed?

Group I: Treatment (nelfinavir, cisplatin, EBRT) Experimental Treatment 3 Interventions

Patients receive nelfinavir PO BID for up to 8 weeks. Starting week 2, patients also receive cisplatin IV over 60-90 minutes once weekly during weeks 2-8. Patients undergo EBRT for 5 consecutive days between weeks 2-8. 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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Cisplatin, approved for testicular cancer treatment, has shown significant gastrointestinal and renal toxicities, but modern antiemetic therapies and hydration have greatly reduced these side effects.

Recent studies have expanded our understanding of cisplatin's pharmacology and mechanism of action, leading to ongoing research into dosage variations, administration methods, and the development of new cisplatin analogues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drugs five years later. Cisplatin. Loehrer, PJ., Einhorn, LH.[2019]

In a phase 1 trial involving 13 patients with locally advanced cervical cancer, the combination of nelfinavir (NFV) and chemoradiation (CRT) was found to be well tolerated, with the higher dose of 1250 mg twice daily established as the recommended phase 2 dose due to fewer toxicities.

Nelfinavir sensitized cervical cancer cells to radiation, leading to increased tumor suppression and apoptosis, with 10 out of 11 evaluable patients remaining disease-free at a median follow-up of 50 months, indicating promising efficacy for further studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 trial of nelfinavir added to standard cisplatin chemotherapy with concurrent pelvic radiation for locally advanced cervical cancer. Garcia-Soto, AE., McKenzie, ND., Whicker, ME., et al.[2022]

In a study of 16 women with recurrent vulvar carcinoma, the combination of cisplatin and vinorelbine showed a 40% objective response rate, with 27% achieving complete responses, indicating its efficacy as a treatment option.

The treatment was well-tolerated, with a median progression-free survival of 10 months and overall survival of 19 months, suggesting it is a viable option for patients who have not previously received chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cisplatin and vinorelbine chemotherapy in recurrent vulvar carcinoma. Cormio, G., Loizzi, V., Gissi, F., et al.[2018]

In a study of 29 patients with locally advanced vulvar cancer treated with chemoradiation, those receiving mitomycin C/5-FU showed a higher clinical complete response rate (64.3%) compared to those treated with cisplatin (41.7%), although this difference was not statistically significant.

The overall survival rate was numerically better for the mitomycin C/5-FU group (59.7%) compared to the cisplatin group (31.7%), suggesting that mitomycin C/5-FU may be a more effective option for younger, healthier patients, despite both treatments having similar recurrence-free survival rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of cisplatin and mitomycin C/5-FU as radiosensitisers in the treatment of locally advanced vulvar cancer: results of a retrospective, observational, single-institutional cohort study. Linz, VC., Schwanbeck, C., Krajnak, S., et al.[2023]

In a study of 58 patients with locally-advanced vulvar carcinoma, the combination of radiation therapy and weekly cisplatin chemotherapy resulted in a high complete clinical response rate of 64%, with 78% of those undergoing surgery also achieving a complete pathological response.

The treatment was generally well-tolerated, with common side effects including leukopenia and radiation dermatitis, indicating that while there are some adverse effects, the overall toxicity was acceptable compared to the efficacy observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of radiation therapy and weekly cisplatin chemotherapy for the treatment of locally-advanced squamous cell carcinoma of the vulva: a gynecologic oncology group study. Moore, DH., Ali, S., Koh, WJ., et al.[2022]

Satraplatin is an orally bioavailable platinum anticancer drug that shows comparable antitumor activity to cisplatin but with a more manageable side-effect profile, making it a promising alternative to traditional intravenous platinum treatments.

Currently undergoing a Phase III trial for hormone-refractory prostate cancer, satraplatin has demonstrated efficacy in various cancers and may provide a new treatment option with fewer serious toxicities than existing platinum-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Satraplatin: an orally available platinum analog for the treatment of cancer. Choy, H.[2022]

In a study of 24 patients with vulvar cancer treated with various forms of radiotherapy, the overall response rate was 55%, with a 5-year disease-free survival rate of 42.2% and an overall survival rate of 46.2%.

Patients who underwent lymph node dissection along with radiotherapy experienced significantly higher rates of severe late complications (50%), while those treated with primary radiotherapy alone had a much lower rate of late complications (16.6%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment outcome in patients with vulvar cancer: comparison of concurrent radiotherapy to postoperative radiotherapy. Lee, J., Kim, SH., Kim, G., et al.[2021]

In two cases of metastatic squamous cell vulvar cancer treated with a cisplatin-gemcitabine chemotherapy regimen, no response was observed, highlighting the limited efficacy of this treatment approach.

There is currently no standard treatment for advanced vulvar cancer, and the authors suggest that exploring new agents may be more beneficial than using combinations of older chemotherapy drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cisplatin-gemcitabine as palliative chemotherapy in advanced squamous vulvar carcinoma: report of two cases. Santeufemia, DA., Capobianco, G., Re, GL., et al.[2022]

CI-973 shows promising efficacy in preclinical models, demonstrating activity comparable or superior to cisplatin and carboplatin, and is effective against cisplatin-resistant cancer cell lines.

In a phase I trial with 28 patients, CI-973 exhibited a favorable safety profile with no renal or auditory toxicity, although mild to moderate nausea and vomiting were common; the maximum tolerated dose was determined to be 290 mg/m2 for patients with good performance status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I clinical evaluation of [SP-4-3(R)]-[1,1-cyclobutanedicarboxylato(2-)](2-methyl-1,4- butanediamine-N,N1) platinum in patients with metastatic solid tumors. Theriault, RL., Cohen, IA., Esparza, L., et al.[2019]

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]

This study proposes a phase II clinical trial to evaluate the combination of pembrolizumab with cisplatin-sensitized radiation therapy in women with unresectable or metastatic vulvar cancer, aiming to enhance anti-tumor immune responses and improve patient outcomes.

The trial is designed to be accessible, allowing patients to receive standard care locally while monitoring for adverse effects and conducting translational studies to assess immune activation, addressing the lack of effective immunotherapy options for this rare cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2 study of combined chemo-immunotherapy with cisplatin-pembrolizumab and radiation for unresectable vulvar squamous cell carcinoma. Yeku, O., Russo, AL., Lee, H., et al.[2021]

In a study using the ME180 cervical cancer cell line, it was found that irradiation significantly decreased the sensitivity of the cells to carboplatin (CBDCA), suggesting that CBDCA may not be effective when given during radiation treatment.

In contrast, nedaplatin (NEP) showed increased sensitivity when administered 8 hours before or after irradiation, indicating that NEP could be a more effective option for concurrent chemoradiotherapy in cervical cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation reduces carboplatin sensitivity and enhances nedaplatin sensitivity in cervical squamous cell carcinoma in vitro. Tanaka, T., Yukawa, K., Umesaki, N.[2020]

This phase-III trial will evaluate the effectiveness of nelfinavir, a protease inhibitor, in improving disease-free survival (DFS) in patients with locally advanced cervical cancer, with a total of 348 participants planned over an 8-year duration.

The study aims to compare DFS between patients receiving standard chemoradiation and those receiving nelfinavir alongside chemoradiation, while also assessing locoregional control, overall survival, and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent chemoradiation and brachytherapy alone or in combination with nelfinavir in locally advanced cervical cancer (NELCER): study protocol for a phase III trial. Chopra, S., Goda, JS., Mittal, P., et al.[2022]

In a phase II trial involving 12 patients with advanced squamous carcinoma of the vulva, concurrent treatment with cisplatin and 5-fluorouracil (5-FU) alongside radiation therapy resulted in a complete tumor response in 67% of patients, with 75% response in stage III and 50% in stage IV cases.

The treatment was well-tolerated, with no treatment-related deaths and no grade 4 toxicity reported, although some patients experienced grade 2 and 3 side effects, indicating that this approach could be a safe alternative to radical surgery for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent cisplatin and 5-fluorouracil chemotherapy and radiation therapy for advanced-stage squamous carcinoma of the vulva. Berek, JS., Heaps, JM., Fu, YS., et al.[2019]

Citations

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Nelfinavir, Cisplatin, and External Beam Radiation Therapy for ... This phase I trial studies the side effects and best dose of nelfinavir when given together with cisplatin and external beam radiation therapy in treating ...

2. mdanderson.org mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2019-0629.html

A Phase I Study of Nelfinavir and Cisplatin chemotherapy ... Giving nelfinavir, cisplatin, and external beam radiation therapy may work better than giving only cisplatin and external beam radiation therapy in treating ...

3. withpower.com withpower.com/trial/nelfinavir-chemoradiation-for-vulvar-cancer-4e94b

Nelfinavir + Chemoradiation for Vulvar Cancer This phase I trial studies the side effects and best dose of nelfinavir when given together with cisplatin and external beam radiation therapy in treating ...

4. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.33449

Phase 1 trial of nelfinavir added to standard cisplatin ... Nelfinavir (NFV), an HIV-1 protease inhibitor, has been shown to sensitize cancer cells to chemoradiation (CRT). The objectives of this ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8391130/

Role of Chemotherapy in Vulvar Cancers: Time to Rethink ... The 2-year overall survival was 36% [23]. A further study reported on the outcome of radiotherapy and 5-fluorouracil alone or in combination ...

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A Phase II Trial of Cisplatin, Gemcitabine, and Intensity ... Weekly C and G concurrent with IMRT sufficiently improved CPR in women with locally advanced vulvar squamous cell carcinoma not amenable to surgical resection.

7. esmoiotech.org esmoiotech.org/article/S2590-0188(23)00237-X/fulltext

102P Interim safety analysis of a phase II trial of cisplatin ... Patients with unresectable or metastatic disease have relatively poor outcomes. Cisplatin and radiation (cis-RT) have been reported to have anti-tumor ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04430699

Cisplatin+Pembrolizumab+RT in Vulvar Cancer This is a single-arm phase 2 clinical trial involving women with unresectable, incompletely resected, recurrent, or metastatic vulva squamous cell carcinoma.

9. translational-medicine.biomedcentral.com translational-medicine.biomedcentral.com/articles/10.1186/s12967-020-02523-5

A phase 2 study of combined chemo-immunotherapy with ... Unresectable or metastatic vulvar cancer has relatively poor outcomes despite chemotherapy-sensitized radiation therapy and combination ...

10. sciencedirect.com sciencedirect.com/science/article/pii/S1048891X24006030

Definitive chemoradiation or radiation therapy alone for the ... 10 Patients with an overall treatment time of 105 days or greater had a median overall survival of 45.4 months, whereas those with an overall treatment time of ...