Chemoradiotherapy for Advanced Vulvar Cancer

(GROINSS-VIII Trial)

Recruiting at 26 trial locations

Overseen By Maaike H Oonk, MD PhD

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: University Medical Center Groningen

Must not be taking: Anticonvulsants, Steroids

Disqualifiers: Other carcinomas, Pelvic radiotherapy, others

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

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

Compensation: Varies

Number of Visits: 5

Duration: 5-6 weeks

157 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment approach for advanced vulvar cancer. Instead of surgically removing lymph nodes, patients will receive a combination of cisplatin (a chemotherapy drug) and targeted radiotherapy. This approach may suit those with a specific type of vulvar cancer and a sentinel lymph node showing cancer spread greater than 2mm, but without large or multiple tumors. Participants should have a single tumor under 4cm, good kidney and liver function, and no history of certain other cancers or heart issues. The trial aims to determine if this treatment can effectively manage the cancer while avoiding surgery. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that using cisplatin with radiotherapy is generally well-tolerated, though it can cause some side effects. Studies have found this combination effective for treating vulvar cancer. However, about half to all patients might experience side effects, ranging from mild to severe, though most can be managed.

For radiotherapy, research indicates it effectively controls cancer in the treated area and reduces the chance of recurrence. While some patients may experience severe long-term side effects, these are uncommon.

Overall, both treatments have been used in various cancer treatments before, so their safety is fairly well understood. Participants should still be aware of possible side effects and discuss these with their healthcare team. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the chemoradiotherapy treatment combining cisplatin and radiotherapy for advanced vulvar cancer because it offers a targeted approach that could enhance effectiveness. Unlike standard treatments, which often involve surgery or standalone radiotherapy, this method uses cisplatin to sensitize cancer cells, making them more susceptible to the effects of radiation. This synergistic approach aims to deliver a higher dose of radiotherapy directly to the tumor while minimizing damage to surrounding healthy tissue. By potentially improving the precision and efficacy of treatment, this combination could offer better outcomes for patients with advanced stages of vulvar cancer.

What evidence suggests that chemoradiotherapy could be an effective treatment for advanced vulvar cancer?

Research has shown that using cisplatin with radiotherapy effectively treats vulvar cancer. In this trial, participants will receive a combination of cisplatin and radiotherapy as part of the chemoradiation treatment arm. One study found that this method significantly reduced or eliminated cancer in many patients. Another study reported that 71% of patients were still alive after three years, and 65% experienced no cancer recurrence with this treatment. These findings suggest that combining chemotherapy and radiation, known as chemoradiation, can be a promising option for advanced vulvar cancer. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with a specific type of vulvar cancer (SCC) that's less than 4cm, not spread to large lymph nodes or other body parts. Participants must have small metastases in sentinel lymph nodes and be healthy enough overall to give consent and follow the study plan.

Inclusion Criteria

Written informed consent

Patients are able to understand requirements of study, provide written informed consent and comply with the study and follow-up procedures

Absolute neutrophil count ≥ 1.5 x 109 /L

Exclusion Criteria

My tumor cannot be removed with surgery and is larger than 4cm.

I haven't had any cancer except for basal cell skin cancer in the last 5 years.

I have had radiation treatment in my pelvic area.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive chemoradiation with a total dose of 56 Gy over 5-6 weeks, combined with weekly cisplatin 40 mg/m2

5-6 weeks

5 visits (in-person) for chemotherapy administration

Follow-up

Participants are monitored for groin recurrence and quality of life for two years after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• Radiotherapy

Trial Overview Patients with certain vulvar cancer will receive chemoradiation therapy instead of surgery to remove groin lymph nodes. The treatment includes Cisplatin, a chemotherapy drug, combined with radiotherapy aimed at reducing cancer spread.

How Is the Trial Designed?

Group I: Chemoradiation Experimental Treatment 2 Interventions

Inguinofemoral radiotherapy (48-50 Gy in 1.8 Gy daily fractions, with a boost dose to the involved inguinal site for a total equivalent dose of 56 Gy over 5-6 weeks, preferably with simultaneous integrated boost technique) combined with weekly cisplatin 40 mg/m2 intravenously on days 1, 8, 15, 22 and 29

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?

University Medical Center Groningen

Lead Sponsor

Trials

770

Recruited

1,101,000+

NRG Oncology

Collaborator

Trials

242

Recruited

105,000+

Dutch Cancer Society

Collaborator

Trials

118

Recruited

77,500+

Published Research Related to This Trial

A phase II study involving 55 patients with locally advanced squamous cell carcinoma of the cervix showed that combining cisplatin (CDDP) with radiotherapy resulted in a high overall response rate of 96%, with 87% achieving complete response.

The 5-year survival rates were promising, particularly for Stage III patients at 67%, indicating that CDDP combined with radiotherapy is a safe and effective treatment option for this cancer, with manageable toxicity and no treatment-related deaths.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mature results of a phase II trial of concomitant cisplatin/pelvic radiotherapy for locally advanced squamous cell carcinoma of the cervix. Fields, AL., Anderson, PS., Goldberg, GL., et al.[2013]

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]

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]

A phase II trial of cisdiammino-dichloro platinum (CDDP) showed significant effectiveness against testis embryonic carcinoma, ovarian carcinoma, and epidermoid cancers, particularly in head and neck and cervical cancers.

While CDDP demonstrates strong anti-cancer activity, it is associated with notable toxicity primarily affecting the digestive and renal systems, leading to its use in combination therapies for the indicated tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cis-diammino-dichloro-platinum therapy of cancers; phase II therapeutic trial]. Hayat, M., Bayssas, M., Brulé, G., et al.[2013]

In a Phase I study involving 40 patients with urologic and gynecologic cancers, cis-diamminedichloroplatinum(II) (CIS-DDP) was found to have manageable side effects, primarily nausea, vomiting, and anorexia, which resolved quickly after stopping the treatment.

The study indicated low levels of hematopoietic and renal toxicities, with no reported cases of hearing disturbances or tinnitus, suggesting a favorable safety profile for CIS-DDP at doses of 50 mg/m2 for single administration and 20 mg/m2/day for five consecutive days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Phase I study of a new antineoplastic agent, cis-diamminedichloroplatinum (II)]. [2013]

In a study of 10 patients with advanced vulvar cancer, treatment with neoadjuvant chemotherapy (paclitaxel and cisplatin) resulted in an 80% clinical response rate, with significant tumor shrinkage observed in most cases.

Despite some patients experiencing severe bone marrow toxicity (40% grade 3-4), this was manageable, and over half of the patients remained alive without disease after a median follow-up of 40 months, suggesting that this treatment approach is both effective and tolerable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of paclitaxel and cisplatin as the neoadjuvant treatment for locally advanced squamous cell carcinoma of the vulva. Raspagliesi, F., Zanaboni, F., Martinelli, F., et al.[2021]

A combination of prolonged continuous infusions of 5-fluorouracil and cisplatin with radiation therapy was well tolerated in 12 patients with advanced vulvar carcinoma, showing virtually no hematologic toxicity and no treatment breaks.

The treatment resulted in a high response rate, with 11 out of 12 patients achieving at least a partial clinical response, and 6 patients remaining disease-free for 17 to 37 months after treatment, indicating its efficacy for massive vulvar carcinomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged continuous infusion cisplatin and 5-fluorouracil with radiation for locally advanced carcinoma of the vulva. Eifel, PJ., Morris, M., Burke, TW., et al.[2022]

In a study involving eight patients with epidermoid carcinoma of the penis, cis-diamminedichloride platinum II (DDP) demonstrated effectiveness, with three out of six adequately treated patients showing an objective response.

One patient achieved complete remission lasting 7 months, while two others had partial remissions of 8 and 2 months, suggesting that DDP is a promising treatment option for penile carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cis-diamminedichloride platinum II (DDP) in the treatment of penile carcinoma. Sklaroff, RB., Yagoda, A.[2019]

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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.5511

Primary results of a phase 2 study of cisplatin-sensitized ... The study met its primary endpoint. Concurrent treatment with chemoradiation and pembrolizumab improved ORR and 6-month RFS in vulvar cancer.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/22079361/

A phase II trial of radiation therapy and weekly cisplatin ... Conclusions: This combination of radiation therapy plus weekly cisplatin successfully yielded high complete clinical and pathologic response rates with ...

3. 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 ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11585925/

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.

5. tro.amegroups.org tro.amegroups.org/article/view/7813/html

Analyses of treatment outcomes in advanced vulvar cancer Another study (18) in 2016 evaluated treatment outcomes of definitive CCRT in vulvar cancer. The 3-year OS was 71%, freedom from local recurrence was 65%, and ...

6. 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.

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

A phase 2 study of combined chemo-immunotherapy with ... Platinum-based combination chemotherapy for advanced or recurrent metastatic vulvar cancer has an overall response rate (ORR) of 40% [4], while ...

8. mdpi.com mdpi.com/2072-6694/17/14/2392

Immunotherapy and Advanced Vulvar Cancer Safety outcomes demonstrated manageable toxicity profiles, with treatment-related adverse events (AEs) occurring in 50.5% to 100% of patients. In 0% to 78.6% of ...