Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Vulvar Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Genital Neoplasms, Female

Urogenital Neoplasms

Vulvar Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Vulvar Cancer

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Cisplatin

Antimetabolites

Patients undergo IMRT 5 days a week for 6 weeks. Patients also receive gemcitabine hydrochloride IV over 30 minutes and cisplatin IV over 60 minutes weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Within 6-8 weeks after completion of chemoradiation patients undergo local core biopsy to confirm response or surgical excision of gross residual disease in the vulva and/or inguinal-femoral lymph nodes.

Gemcitabine Hydrochloride

Intensity-Modulated Radiation Therapy

Undergo local core biopsy or surgical excision

Therapeutic Conventional Surgery

Neil S Horowitz

This phase II trial studies how well radiation therapy works when given with gemcitabine hydrochloride and cisplatin work in treating patients with squamous cell cancer of the vulva that has spread from where it started to nearby tissue or lymph nodes. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy, such as gemcitabine hydrochloride and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving radiation therapy together with gemcitabine hydrochloride and cisplatin may kill more tumor cells.

PRIMARY OBJECTIVES:

I. To determine the efficacy of cisplatin, gemcitabine (gemcitabine hydrochloride), and intensity-modulated radiation therapy (IMRT) in achieving a complete pathologic response when used for the primary treatment of locally-advanced squamous cell carcinoma of the vulva.

SECONDARY OBJECTIVES:

I. To determine the efficacy of cisplatin, gemcitabine, and IMRT in achieving a complete clinical response when used for the primary treatment of locally-advanced squamous cell carcinoma of the vulva.

II. To determine the vulvar progression-free survival and groin progression-free survival in women treated with cisplatin, gemcitabine and IMRT for locally advanced vulvar carcinoma.

III. To determine the toxicity and surgical morbidity of the combined modality approach of cisplatin, gemcitabine and IMRT followed by reduced-scope surgery for the treatment of locally-advanced vulvar carcinoma.

OUTLINE:

Patients undergo IMRT 5 days a week for 6 weeks. Patients also receive gemcitabine hydrochloride intravenously (IV) over 30 minutes and cisplatin IV over 60 minutes weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Within 6-8 weeks after completion of chemoradiation patients undergo local core biopsy to confirm response or surgical excision of gross residual disease in the vulva and/or inguinal-femoral lymph nodes.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Radiation Therapy, Gemcitabine Hydrochloride, and Cisplatin in Treating Patients With Locally Advanced Squamous Cell Cancer of the Vulva

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 (NCT #01595061)

Percentage of participants with complete pathologic response. Complete pathologic response is defined as negative local core biopsy or FNA specimens following primary chemo-radiation therapy.

Percentage of participants with complete clinical response. Complete clinical response is defined as no clinical/radiographic evidence of primary disease (vulva or groin) following primary chemo-radiation therapy.

Number of participants with a maximum grade of 3 or higher during treatment period. Adverse events are graded and categorized using CTCAE v4.0.

Estimate for probability of progression free survival by Kaplan-Meier method, where progression-free survival is defined as the period of time from study entry to time of disease progression, death or date of last contact, whichever occurs first. PFS is censored in patients who are alive and have not progressed. Progression is assessed by RECIST 1.1

National Cancer Institute (NCI)

Gynecologic Oncology Group

Gemcitabine 50 mg/m2 and Cisplatin 40mg/m2 administered weekly throughout IMRT 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.

GEM+CIS+IMRT

20 - 29 years

30 - 39 years

40 - 49 years

50 - 59 years

60 - 69 years

70 - 79 years

>= 80 years

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Linda Gedeon for Wei Deng

Complete Pathologic Response

Complete Clinical Response

Leukopenia

Thrombocytopenia

Neutropenia

Anemia

Other Investigations

Other blood and lymphatic disorders

Cardiac disorders

Gastrointestinal disorders

General disorders and administration site conditions

Infections and infestations

Injury, poisoning and procedural complications

Metabolism and nutrition disorders

Musculoskeletal and connective tissue disorders

Peripheral sensory neuropathy

Other nervous system disorders

Renal and urinary disorders

Reproductive system and breast disorders

Respiratory, thoracic and mediastinal disorders

Skin and subcutaneous tissue disorders

Surgical and medical procedures

Vascular disorders

Adverse Events (Grade 3 or Higher) During Treatment Period

Progression-free Survival (PFS)

Overall Study

Symptoms and General Pathology

Digestive System Diseases

Skin and Connective Tissue Diseases

Mouth and Tooth Diseases

Recurrence

Esophageal Neoplasms

Melanoma

Vaginal Neoplasms

Mouth Neoplasms

Disease Attributes

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Mouth Diseases

Stomatognathic Diseases

Vaginal Diseases

Esophageal Cancer

Vaginal Cancer

Oral Cancer

Neuroendocrine Tumor

Neuroepithelioma

Nivolumab

Antibodies

Antibodies, Monoclonal

Ipilimumab

Immunoglobulins

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

PART I: Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1. Within 3-6 weeks after receiving nivolumab and ipilimumab, patients undergo surgery per standard of care. Within 84 days of last surgical resection, patients may also undergo adjuvant RT, if clinically appropriate.

PART II: Patients undergo active surveillance for 1 year.

PART I: Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1. Within 3-6 weeks after receiving nivolumab and ipilimumab, patients undergo surgery per standard of care. Within 84 days of last surgical resection, patients may also undergo adjuvant RT, if clinically appropriate.

PART II: Patients receive nivolumab IV over 30 minutes once every 2 weeks for 4 doses. Patients then continue to receive nivolumab IV over 30 minutes once every 4 weeks for up to 11 doses in the absence of disease progression or unacceptable toxicity.

Conventional Surgery

Laboratory Biomarker Analysis

Patient Observation

Radiation Therapy

Alexander Shoushtari

This randomized phase II trial studies how well nivolumab or expectant observation following ipilimumab, nivolumab, and surgery work in treating patients with high-risk mucosal melanoma that is restricted to the site of origin without evidence of spread, has spread to a local and regional area of the body, or has come back. Monoclonal antibodies, such as nivolumab and ipilimumab, may interfere with the ability of tumor cells to grow and spread. Sometimes the mucosal melanoma may not need more treatment until it progresses. In this case, observation may be sufficient. It is not known if nivolumab or expectant observation following ipilimumab, nivolumab, and surgery may be better in treating patients with mucosal melanoma.

PRIMARY OBJECTIVES:

I. Recurrence free survival (RFS) in patients with mucosal melanoma (MM) treated with neoadjuvant ipilimumab plus nivolumab and surgery followed by adjuvant nivolumab and expectant observation.

SECONDARY OBJECTIVES:

I. Pathologic complete response with neoadjuvant ipilimumab plus nivolumab. II. Distant recurrence-free survival (DRFS) with adjuvant nivolumab and expectant observation.

III. Overall survival (OS) with adjuvant nivolumab and expectant observation. IV. Safety/toxicity as measured by maximum grade adverse event in (a) the neoadjuvant setting, (b) the adjuvant nivolumab cohort after randomization, and (c) the observation cohort after randomization.

V. Rate of delayed primary surgery.

TERTIARY OBJECTIVES:

I. Demonstrate that baseline tumors harboring a higher neoepitope burden have superior median RFS than those who have a lower neoepitope burden in the arm receiving adjuvant nivolumab.

II. Demonstrate that tumors with higher CD8+ infiltration at the tumor invasive margin at surgical resection have superior median RFS than those with lower CD8+ infiltration.

III. Demonstrate that tumors harboring a "T cell inflamed" ribonucleic acid (RNA) expression signature at surgical resection following neoadjuvant nivolumab plus ipilimumab have a superior distant RFS than those harboring a "non-T cell inflamed" signature, both in the overall group and within those who receive adjuvant nivolumab.

IV. Identify recurrent genetic alterations at baseline that are associated with higher CD8+/PD1+ infiltration at baseline and following 1 dose of neoadjuvant nivolumab plus ipilimumab.

V. Tumor response rate will be estimated based on patients whose imaging are captured and submitted during the neo-adjuvant portion of the study (imaging is not required).

OUTLINE:

PART I: Patients receive nivolumab intravenously (IV) over 30 minutes and ipilimumab IV over 30 minutes on day 1. Within 3-6 weeks after receiving nivolumab and ipilimumab, patients undergo surgery per standard of care. Within 84 days of last surgical resection, patients may also undergo adjuvant radiation therapy (RT), if clinically appropriate.

PART II: Within 84 days of last surgical resection, patients are randomized to 1 of 2 arms.

ARM I: Patients undergo active surveillance for 1 year.

ARM II: Patients receive nivolumab IV over 30 minutes once every 2 weeks for 4 doses. Patients then continue to receive nivolumab IV over 30 minutes once every 4 weeks for up to 11 doses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 90 days for 2 years, every 180 days for 3 years or until disease progression, whichever is first, and every 6 months thereafter until a maximum of 5 years following registration.

Nivolumab or Expectant Observation Following Ipilimumab, Nivolumab, and Surgery in Treating Patients With High Risk Localized, Locoregionally Advanced, or Recurrent Mucosal Melanoma

A Randomized Phase II Trial of Adjuvant Nivolumab or Expectant Observation Following Neoadjuvant Ipilimumab Plus Nivolumab and Surgical Resection of High-Risk Localized, Locoregionally Advanced, or Recurrent Mucosal Melanoma

CD8+ infiltration levels will be compared to RFS times using a cox proportional hazards model.

Neoepitope burden will be compared to RFS using a cox proportional hazards model.

The rate of pathologic complete response will be estimated using and a 95% confidence interval will be calculated using properties of the binomial distribution.

Patients will be categorized by driver mutation, including BRAF, RAS family (NRAS/KRAS/HRAS), KIT, and/or NF1 alterations. The degree of CD8+ and/or PD-L1 infiltration will be compared across various categories of driver mutation using descriptive statistics. Pending further advances in genomic understanding of these tumors, alternate categories may be constructed.

Patients will be categorized has having a "T dell inflamed" RNA expression signature versus a "non-T cell inflamed" signature. These groups will be compared to each other in terms of RFS times using a cox proportional hazards model. An additional model will be constructed with randomized arm included to determine if there is an interaction between signature and arm.

RFS of patients receiving adjuvant nivolumab will be compared to patients undergoing observation. Kaplan- Meier curves will be constructed and median RFS times will be calculated for each arm.

Will be evaluated using the Kaplan- Meier method. Median times to DRFS will be calculated for each arm and a cox proportional hazards model will be constructed to determine if there is a DRFS benefit for patients in the adjuvant Nivolumab arm (compared to observation).

Maximum grade adverse events will be summarized in each of the following settings: during the neo-adjuvant phase of the trial (i.e. from registration until a patient is randomized to adjuvant nivolumab or observation), the adjuvant nivolumab arm after randomization, he observation arm after randomization.

Will be evaluated using the Kaplan- Meier method. Median OS times will be calculated for each arm and a cox proportional hazards model will be constructed to determine if there is a DRFS benefit for patients in the adjuvant Nivolumab arm (compared to observation).

Reasons for delay will be summarized and the rate of delay will be calculated along with a 95% confidence interval using the properties of the binomial distribution.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Radiation Therapy, Gemcitabine Hydrochloride, and Cisplatin in Treating Patients With Locally Advanced Squamous Cell Cancer of the Vulva	NCT01595061	Stage III Vulva... Stage IIIA Vulv... Stage IIIB Vulv... Stage IIIC Vulv... Stage IVA Vulva... Vulvar Squamous...	Cisplatin Gemcitabine Hyd... Intensity-Modul... Therapeutic Con...	18 Years -	GOG Foundation
Nivolumab or Expectant Observation Following Ipilimumab, Nivolumab, and Surgery in Treating Patients With High Risk Localized, Locoregionally Advanced, or Recurrent Mucosal Melanoma	NCT03220009	Cervical Carcin... Esophageal Carc... Mucosal Melanom... Mucosal Melanom... Oral Cavity Muc... Recurrent Melan... Stage II Vulvar... Stage III Vulva... Stage IIIA Vulv... Stage IIIB Vulv... Stage IIIC Vulv... Stage IV Oral C... Stage IV Vulvar... Stage IVA Oral ... Stage IVB Oral ... Stage IVC Oral ... Vaginal Carcino...	Conventional Su... Ipilimumab Laboratory Biom... Nivolumab Patient Observa... Radiation Thera...	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for stage iiic vulvar cancer ajcc v7