GOG 0279: A PHASE II TRIAL EVALUATING CISPLATIN (NSC #119875) AND GEMCITABINE (NSC #613327) CONCURRENT WITH INTENSITY-MODULATED RADIATION THERAPY (IMRT) IN THE TREATMENT OF LOCALLY ADVANCED SQUAMOUS CELL CARCINOMA OF THE VULVA

Study ID
STU 122012-016

Cancer Related
Yes

Healthy Volunteers
No

Study Sites

Contact
Annette Paulsen
214-648-2290
annette.paulsen@utsouthwestern.edu

Principal Investigator
David Miller

Summary

This is a two-stage single cohort, multi-center, phase ii clinical trial to access efficacy and toxicity of weekly
chemotherapy (CT) and radiation (RT) in patients with locally advanced vulvar cancer (T3 or T4, n0 x n3, M0) not amenable to surgery.

all patients who are eligible for this protocol with T2 or T3 primary tumors (n0-3, M0) not amenable to surgical resection by standard radical vulvectomy will be treated according to this regimen. There is no randomization.

Surgery: Patients with clinically negative or resectable groin nodes will undergo pretreatment inguinal x femoral lymph node dissection or sentinel lymph node biopsy at the discretion of the treating surgeon. Six to 8 weeks following completion of chemoradiation patients will undergo local core biopsy of the tumor bed to confirm
complete pathologic response or surgical excision of gross residual disease in the vulva and/or inguinal-femoral lymph nodes. if the inguinal x femoral lymph nodes were initially deemed unresectable, an Fna of persistent clinical or radiographic suspicious lymph nodes 6-8 weeks after completion of radiation is acceptable. if the Fna is
positive, a targeted excision of the groin should be done. a radical vulvectomy is not necessary. if there has been complete clinical response, an excisional biopsy of the primary tumor site to confirm pathologic response should be performed.

Radiation: Radiation therapy will be delivered by iMRT to the vulva, inguinal-femoral lymph nodes, and lower pelvic lymph nodes to begin within 4-6 weeks after inguinalfemoral node dissection or determination of unresectable nodes.
- The vulvar CTV will receive 64 Gy regardless of the groin node dose.
- Patients with negative groin nodes as determined by pretreatment inguinal x femoral lymph node dissection will receive radiation therapy to the vulva and may receive radiation therapy to the inguinal x femoral and lower pelvic lymph nodes at the discretion of the treating physician. if treatment to the groins/low pelvis is elected, the total dose will be 45 Gy.

- For those with positive lymph nodes by inguinal xfemoral lymph node dissection, radiation will be delivered to a dose of 50 Gy and with a boost to 60 Gy on any/both sides that have high risk nodal features. These features include
those inguinal nodes affected by [GreaterThanorequalTo] 3(+) Ln, extracapsular extension, or close/positive margin. For those patients with unresectable lymph nodes, patients will receive radiation to a dose of 64 Gy.

Post-Radiation evaluation: an Fna of any clinical or radiographic residual disease in the groin or vulva will be performed 6-8 weeks after completing radiation. Those that have a positive Fna will undergo a targeted excision.
Chemotherapy: Patients will receive concurrent Cisplatin 40 mg/m2 and Gemcitabine 50 mg/m2 administered weekly throughout radiation therapy. Gemcitabine will be infused prior to cisplatin and given over approximately 30 minutes while the cisplatin will be delivered over approximately 60 minutes.

Primary endpoint is complete partologic response (pCR), defined among patients who experienced a complete clinical resonse and had a negative local core biopsy or Fna.
in addition, the following endpoints and data elements will be used to evaluate primary, secondary, and/or translational research objectives:
Complete clinical response (cPR) is defined as no clinical/radiographic evidence
of primary disease (vulvar or groin) following chemo-radiation therapy.
incidence and severity of adverse effects as assessed by CTCae v4.0
Progression free survival (PFS)
Site(s) of recurrence/relapse (local, loco-regional or distant)
Regarding treatment compliance: treatment span, incidence and duration of
treatment delay, reasons for delays, chemotherapy dose, radiation dose and
reasons for dose level reductions
Baseline patient characteristics: age, performance status, race and ethnicity

Participant Eligibility

3.11 Patients with locally-advanced, previously untreated squamous cell carcinoma of the vulva.
3.12 Patients with T2 or T3 primary tumors (N0-3, M0) not amenable to surgical resection by
standard radical vulvectomy.
3.13 Patients must have adequate:
3.131 Bone marrow function: Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl Platelets greater than or equal to 100,000/mcl.
3.132 Renal function: Creatinine <= 1.5 x institutional upper limit normal (ULN) or calculated
creatinine clearance >= 60 ml/min.
3.133 Hepatic function: Bilirubin <= 1.5 x ULN. AST and ALT <= 3.0 x ULN and alkaline phosphatase
<= 3.0 x ULN.
3.14 Patients judged capable of tolerating a radical course of chemoradiation therapy.
3.15 Patients must not be eligible for a higher priority GOG protocol, if one exists. In general, this would refer to any active GOG Phase III protocol or Rare Tumor protocol for the same patient population.
3.16 Patients who have met the pre-entry requirements specified in Section 7.0.
3.17 Patients must have signed an approved informed consent and authorization permitting release
of personal health information.
3.18 Patients must be 18 years or older.
3.19 Patients with a GOG Performance Status of 0, 1 or 2