Chemoradiotherapy for Advanced Vulvar Cancer

(GROINSS-VIII Trial)

Recruiting at26 trial locations

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University Medical Center Groningen

Must not be taking: Anticonvulsants, Steroids

Disqualifiers: Other carcinomas, Pelvic radiotherapy, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing a combination of chemotherapy and radiation therapy for early-stage vulvar cancer patients with larger or multiple metastases. The goal is to find a less invasive but effective alternative to surgery. The treatment uses drugs and high-energy rays to kill cancer cells.

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.

What data supports the effectiveness of the treatment for advanced vulvar cancer?

Research shows that combining cisplatin with radiation therapy can be effective for treating advanced vulvar cancer, with many patients experiencing a reduction in tumor size and some remaining disease-free for months after treatment. ^{1 2 3 4 5}

Is chemoradiotherapy with cisplatin safe for humans?

Cisplatin, used in combination with radiotherapy, has been studied for various cancers and is generally safe for humans, though it can cause side effects like nausea, vomiting, and kidney issues. These side effects are often manageable with modern treatments and precautions. ^{3 6 7 8 9}

How does the chemoradiotherapy treatment for advanced vulvar cancer differ from other treatments?

This treatment combines cisplatin, a drug that makes cancer cells more sensitive to radiation, with radiotherapy to improve outcomes for advanced vulvar cancer, which lacks a standard treatment. Unlike other regimens, this approach aims to achieve a complete response by using cisplatin's radiosensitizing properties, potentially reducing the need for extensive surgery. ^{1 2 3 4 5}

Research Team

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Cisplatin (Alkylating agents)
• Radiotherapy (Radiation)

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.

Participant Groups

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 Canada, Japan for the following indications:

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+

Henk Heidekamp

University Medical Center Groningen

Chief Executive Officer since 2014

MSc in Toxicology and Nutrition from the Open University of the Netherlands

Paulina Snijders

University Medical Center Groningen

Chief Medical Officer since 2023

MD

NRG Oncology

Collaborator

Trials

242

Recruited

105,000+

Stephanie Gaillard

NRG Oncology

Chief Medical Officer

MD from Johns Hopkins University

Norman Wolmark

NRG Oncology

Chief Executive Officer since 2023

MD from Harvard Medical School

Dutch Cancer Society

Collaborator

Trials

118

Recruited

77,500+

Carla van Gils

Dutch Cancer Society

Chief Executive Officer since 2023

PhD in Molecular Biology, Utrecht University

Edward Nieuwenhuis

Dutch Cancer Society

Chief Medical Officer

MD, Erasmus University Rotterdam

Findings from Research

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 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 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 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 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]

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 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]

References

1. United States 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. [2022]

2. Korea (South) pubmed.ncbi.nlm.nih.gov

Role of paclitaxel and cisplatin as the neoadjuvant treatment for locally advanced squamous cell carcinoma of the vulva. [2021]

3. United States 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. [2013]

4. Singapore pubmed.ncbi.nlm.nih.gov

Cisplatin-gemcitabine as palliative chemotherapy in advanced squamous vulvar carcinoma: report of two cases. [2022]

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

Prolonged continuous infusion cisplatin and 5-fluorouracil with radiation for locally advanced carcinoma of the vulva. [2022]

6. France pubmed.ncbi.nlm.nih.gov

[Cis-diammino-dichloro-platinum therapy of cancers; phase II therapeutic trial]. [2013]

7. Japan pubmed.ncbi.nlm.nih.gov

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

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

Cis-diamminedichloride platinum II (DDP) in the treatment of penile carcinoma. [2019]

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

Drugs five years later. Cisplatin. [2019]