CRAVAT

Samenvatting

Treatment of metastatic vulvar carcinoma  with Carboplatin and Paclitaxel chemotherapy (CRAVAT).

Doel

Respons op chemotherapie bij patiënten met een gemetastaseerd vulvacarcinoom.
Patiënten krijgen zes kuren chemotherapie, waarbij na drie kuren response valuatie door middel van lichamelijk onderzoek en een CT-scan zal plaatsvinden. Voorafgaand aan de start van de chemotherapie zal een operatie van de liesklieren plaatsvinden indien geïndiceerd.
Patiënten zullen gevraagd worden om 3 extra biopten te laten afnemen voor translationeel onderzoek. Na het afronden van de chemokuren, kan een operatie in palliatieve setting overwogen worden.

Eindpunten

Primair:

  • response rate en tumor reductie na neo adjuvante chemotherapie tvv exenteratieve chirurgie
  • verkrijgen van voldoende vrije snijvlakken bij (een orgaansparende) ruime lokale excisie
  • meten van morbiditeit en complicaties

Secundair:

  • lokale controle vulva
  • ziektevrije en overall overleving
  • patroon van recidief
  • evaluatie microscopische response

Inclusie criteria

  • Woman ≥ 18 years
  • Signed and written informed consent.
    Note: written and signed informed consent will be obtained before any study procedures, including study-specific-screening procedures, has been performed.
  • Histologically confirmed squamous cell vulvar carcinoma
  • Histologically or CT scan confirmed metastatic squamous cell vulvar carcinoma
  • Measurable disease (by physical examination and computer tomography)
  • World Health Organization performance status of 0-2
  • Adequate hematological function defined by platelet count >75x10E9/L, absolute neutrophil count ANC >1.5x10E9/L, and hemoglobin >6.0 mmol/L.
  • Adequate hepatic function defined by a total bilirubin level ≤1.5x the upper limit of normal (ULN) range and AST and ALT levels ≤2.5x ULN for all subjects.
  • Adequate renal function defined by an estimated creatinine clearance ≥30mL/min according to the Cockroft-Gault formula (or local institutional standard method)
  • Negative pregnancy test for woman of childbearing potential
  • Highly effective contraception for patients if the risk of conception exists.
  • Lesion previously not irradiated
  • TNM stage any T any N M1

Exclusie criteria

  • Vulvar cancer other than squamous cell carcinoma at biopsy
  • Any psychiatric condition that would prohibit the understanding or rendering of informed consent
  • Previous radiotherapy of the vulva, groins or pelvis
  • Patients with metastasis limited to the pelvic lymph nodes, who can be primarily operated with curative intent
  • Other diagnosis of malignancy or evidence of other malignancy for 5 years before screening for this study (except non-melanoma skin cancer, DCIS or low grade breast cancer).

Randomisatie

The aim is an inclusion of 12 patients in order to assess the efficacy and feasibility of treatment with carboplatin and paclitaxel. Currently, the expected number of patients eligible for inclusion is low, caused by rarity and low incidence of the disease (1-4), hence randomization and statistical analysis do not seem achievable.

Flowchart

Patients with metastasized vulvar cancer will be treated with (neo-adjuvant) chemotherapy and the effect of carboplatin/paclitaxel on tumour size will be investigated. If there is response of the tumour after 3 courses of chemotherapy (measured by CT scan and physical examination), a total of 6 courses can be given. Operation of the primary tumour after 3-6 courses is a possibility but only in a palliative setting.

Aanvullende onderzoeken bij randomisatie of tijdens de studie

  • After third course chemotherapy extra outpatient visit for checking response tumor
  • Blood sample and tumor biopsy for translational research optional
  • Pregnancy test
  • Laboratory testing before every cycle of chemotherapy
  • (PET)-CT scan thorax and abdomen before start chemotherapy and after 3 courses of chemotherapy

Follow-up

Every 3 months in the first 2 years, every 6 months in the 3rd and 4th year and subsequently every 6 to 12 months. Vital signs and Adverse events according to CTCAE 5.0 will be monitored.

Contactgegevens

Afdeling Gynaecologie
Antoni van Leeuwenhoek Ziekenhuis
Plesmanlaan 121
1066 CS AMSTERDAM
Tel 020 512 2975

Vermelding in trialregister

CCMO: https://www.toetsingonline.nl/to/ccmo_search.nsf/searchform?OpenForm
Nederlands Trialregister: www.trialregister.nl
Trialregister (Engels): http://www.clinicaltrials.gov

Wordt binnenkort ingediend bij METC.
Sponsor: Antoni van Leeuwenhoek ziekenhuis

30 december 2019