Vulcanize

Samenvatting

Treatment of locally advanced VULvar CArcinoma in a Neoadjuvant setting with Carboplatin and Paclitaxel chemotherapy (VULCANize).

Hypothese

Door patiënten met locally advanced vulvacarcinoom te behandelen met neoadjuvante chemotherapie wordt de kans op een exenteratieve ingreep verminderd en orgaansparend verhoogd.

Eindpunten

Primair:

  • Response rate en tumor reductie na neo adjuvante chemotherapie tvv exenteratieve chirurgie
  • Verkrijgen van voldoende vrije snijvlakken met 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
  • Locally advanced vulvar cancer, either inoperable or requiring exenterative surgery in order to perform a complete resection, or organ-threatening vulvar cancer, which involves the clitoris and/or urethra and/or anus, requiring surgery of the threatened organ in order to achieve a complete resection
  • World Health Organization performance status of 0-2
  • Adequate hematological function defined by platelet count >100x10E9/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.
  • Measurable disease by physical examination

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
  • 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

We aim to include 51 patients. After inclusion of 26 patients an interim analysis will be performed in order to analyse the effectiveness of neoadjuvant chemotherapy. The expected number of patients eligible for inclusion is low, caused by rarity and low incidence of the disease (1-4), hence randomization does not seem achievable.

Flowchart

Patients with inoperable primary or recurrent vulvar cancer or vulvar cancer involving clitoris/urethra/anus. Analysis of involvement of clitoris/urethra/anus, extensiveness of the disease and/or inoperability will be evaluated by the treating physician on the outpatient clinic. This evaluation will be reported in the patient chart and will be discussed during a multidisciplinary meeting. The effect of neoadjuvant carboplatin and paclitaxel is measured to see if patients are operable or can avoid exenterative surgery after 3 (or if necessary up to 6) courses of chemotherapy or operable without affecting clitoris/urethra/anus. After 3 courses of carboplatin and paclitaxel, effect will be measured by physical examination. If response is sufficient, an operation can be planned 4 to 6 weeks after 3rd course chemotherapy. If response is visible but not enough for an organ-sparing operation, a 4th (with a maximum of 6) course(s) of chemotherapy can be given. In this case the operation will be planned 4 to 6 weeks after the last course of chemotherapy.

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

Follow-up schema

Indien geopereerd, is er een nacontrole 6 weken na de operatie.
Vervolgens eerste 2 jaar a 3 maanden.
In 3e en 4e jaar iedere 6 maanden.
Vervolgens iedere 6 of 12 maanden.

Aanvullende onderzoeken bij randomisatie of tijdens de studie

Er kan door de patiënte toestemming gegeven worden tot het afnemen van een extra biopt voorafgaande aan de start neo adjuvante chemotherapie voor NGS. Dit om te onderzoeken welke tumorkarakteristieken aangeven dat een patiënt baat zou kunnen hebben bij deze behandeling.

Accrual

3 jaar

Contactgegevens

Dept of Gynecological Oncology
Antoni van Leeuwenhoek
Plesmanlaan 121
1066 CX Amsterdam
Tel 020 512 2975

Vermelding in trialregister, bv

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

Sponsor: Antoni van Leeuwenhoek ziekenhuis
30 december 2019