Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Carcinoma in Situ

Squamous Intraepithelial Lesions of the Cervix

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Cervical Intraepithelial Neoplasia

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Anti-Inflammatory Agents

Analgesics

Reproductive Control Agents

Gastrointestinal Agents

Micronutrients

Cyclophosphamide

Indomethacin

Omeprazole

Vitamins

Zinc

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antacids

Anti-Ulcer Agents

Proton Pump Inhibitors

Enzyme Inhibitors

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Tocolytic Agents

Cyclooxygenase Inhibitors

Patients receive cyclophosphamide IV on day 1 and IRX-2 via submucosal injections in the cervix or SC for vulvar lesions on days 4-7. Patients also receive indomethacin PO TID, zinc-containing multivitamins PO QD and omeprazole PO on days 1-21. Treatment repeats every 6 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Beginning week 25, patients undergo surgical resection.

Patients receive cyclophosphamide IV on day 1 and placebo via submucosal injections in the cervix or SC for vulvar lesions on days 4-7. Patients also receive indomethacin PO TID, zinc-containing multivitamins PO QD and omeprazole PO on days 1-21. Treatment repeats every 6 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Beginning week 25, patients undergo surgical resection.

IRX-2

Laboratory Biomarker Analysis

Multivitamin

Placebo

Therapeutic Conventional Surgery

Lynda Roman, MD

This randomized phase II trial studies how well an IRX-2 Regimen works in treating women with cervical squamous intraepithelial neoplasia 3 or squamous vulvar intraepithelial neoplasia 3. The IRX-2 Regimen consists of a single dose of cyclophosphamide, followed by 21 days of indomethacin, zinc-containing multivitamins, and omeprazole. IRX-2, a human cell-derived biologic with multiple active cytokine components, may act as an immune booster to stimulate the immune system. Giving cyclophosphamide and IRX-2 may work better at treating cervical squamous intraepithelial neoplasia or squamous vulvar intraepithelial neoplasia.

PRIMARY OBJECTIVES:

I. To compare the proportion of subjects who achieve a pathologic complete response (CR) or partial response (PR) in regimen 1 versus regimen 2 at week 25, based on the resected surgical specimen.

SECONDARY OBJECTIVES:

I. To evaluate the toxicity and feasibility of administration of IRX-2 in subjects with confirmed cervical intraepithelial neoplasia (CIN) 3 or vulvar intraepithelial neoplasia (VIN) 3.

II. To evaluate multiple parameters to assess the activity of the IRX-2 regimen for the treatment of CIN 3 or VIN 3: the occurrence of clinical CRs or PRs at weeks 6, 13 and 25.

III. To evaluate multiple parameters to assess the activity of the IRX-2 regimen for the treatment of CIN 3 or VIN 3: frequency of elimination of human papillomavirus (HPV) in cervical or vulvar tissue using a commercial HPV genotyping assay and viral load determination by quantitative polymerase chain reaction (PCR).

IV. To evaluate multiple parameters to assess the activity of the IRX-2 regimen for the treatment of CIN 3 or VIN 3: analysis of the immune infiltrates in the resected surgical specimens.

V. To evaluate multiple parameters to assess the activity of the IRX-2 regimen for the treatment of CIN 3 or VIN 3: immunophenotypic analysis of peripheral blood lymphocytes.

VI. To evaluate multiple parameters to assess the activity of the IRX-2 regimen for the treatment of CIN 3 or VIN 3: frequency of serum antibodies to HPV E6, E7 and L1 proteins by enzyme-linked immunosorbent assay (ELISA).

VII. To evaluate multiple parameters to assess the activity of the IRX-2 regimen for the treatment of CIN 3 or VIN 3: ribonucleic acid (RNA) expression profiling of immune-inflammatory markers from post-treatment resected surgical specimens.

OUTLINE: Patients are randomized to 1 of 2 arms.

Arm I: Patients receive cyclophosphamide intravenously (IV) on day 1 and IRX-2 via submucosal injections in the cervix or subcutaneously (SC) for vulvar lesions on days 4-7. Patients also receive indomethacin orally (PO) three times daily (TID), zinc-containing multivitamins (PO) once daily (QD) and omeprazole orally (PO) on days 1-21.

Arm II: Patients receive cyclophosphamide IV on day 1 and placebo via submucosal injections in the cervix or SC for vulvar lesions on days 4-7. Patients also receive indomethacin PO TID, zinc-containing multivitamins PO QD and omeprazole PO on days 1-21.

In both arms, treatment repeats every 6 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Beginning week 25, patients undergo surgical resection.

After completion of study treatment, patients are followed up at 1-8 weeks after surgery.

IRX-2 Regimen in Treating Women With Cervical Squamous Intraepithelial Neoplasia 3 or Squamous Vulvar Intraepithelial Neoplasia 3

A Two-Cohort Randomized Phase 2 Trial of the IRX-2 Regimen in Women With Squamous Cervical Intraepithelial Neoplasia 3 (CIN 3) or Vulvar Intraepithelial Neoplasia 3 (VIN 3)

Complete Response (CR) is defined as absence of intraepithelial neoplasia, Partial Response (PR) is defined as a lower grade of dysplasia than present at baseline (for example, grade 3 decreasing to grade 1).

Will be assessed by the incidence and severity of adverse events, serious adverse events, as classified and graded according to the current version of the Common Terminology Criteria for Adverse Events version 4.

National Cancer Institute (NCI)

Brooklyn ImmunoTherapeutics, LLC

University of Southern California

Uterine Cervical Dysplasia

Precancerous Conditions

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 6 weeks for 4 cycles (24 weeks).

Maria Garcia-Jimenez, MD

Rosleen Mala

John A. Glaspy, MD

John A Glaspy, MD

This phase II trial studies the effect of pembrolizumab on cervical intraepithelial neoplasia. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

PRIMARY OBJECTIVE:

I. Proportion of subjects with pathologic complete response (no evidence of dysplasia).

SECONDARY OBJECTIVES:

I. Safety and tolerability of pembrolizumab in subjects with cervical intraepithelial neoplasia (CIN).

II. Proportion of subjects with pathologic partial response (regression to a lower grade of dysplasia).

EXPLORATORY OBJECTIVES:

I. Evaluation of Programmed Death-Ligand 1 (PD-L1) expression in CIN lesions as a biomarker of response to therapy.

II. Evaluation of Human Papillomavirus (HPV) status as a biomarker of response to therapy.

III. Evaluation of HPV clearance as a surrogate endpoint.

OUTLINE:

Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 6 weeks for 4 cycles (24 weeks).

Pembrolizumab for the Treatment of Cervical Intraepithelial Neoplasia

A Phase II Open-Label, Single Arm Pilot Study to Evaluate the Safety and Efficacy of Pembrolizumab for High-Grade Cervical Intraepithelial Neoplasia

Will correlate PD-L1 positivity with response to pembrolizumab.

Assess percentage of subjects who respond to treatment who are HPV positive (using p16 positivity from pathology) compared to percentage of subjects who respond to treatment who are HPV negative in order to evaluate if HPV positivity correlates with improved response to treatment.

Will evaluate HPV clearance as a surrogate endpoint.

Will assess the percent of patients with pathologic complete response at 6 months.

Merck Sharp & Dohme LLC

Jonsson Comprehensive Cancer Center

Uterine Cervical Neoplasms

Carcinoma, Adenosquamous

Neoplasms, Squamous Cell

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Antibodies

Antibodies, Monoclonal

Nimotuzumab

Cisplatin

Immunoglobulins

Patients receive nimotuzumab combined with cisplatin and undergo external-beam radiation and brachytherapy as the patients in experimental group.

Patients receive cisplatin and undergo external-beam radiation and brachytherapy as the patients in control group.

Patients receive nimotuzumab IV over 90 minutes on days 1, 8, 15, 22, 29, 36,43.

Patients undergo cisplatin, 25-40 mg/m2 a week for 4 or 5weeks

Patients undergo pelvic EBRT once daily, 5 days a week, for 5 weeks for a total of 45-50.4Gy

external-beam radiation

high-dose rate brachytherapy,6Gy once weekly,for a total of 24-30Gy

brachytherapy

junguo bu, doctor

jiqiang li, doctor

junguo bu, MD

jiqiang li, MD

The purpose of this phase II trial is to determine the feasibility and efficacy of nimotuzumab combined with concurrent chemoradiotherapy for initially inoperable locally advanced cervical squamous cell carcinoma.

This phase II trial is studying how well giving nimotuzumab together with radiation therapy and cisplatin works in treating patients with previously untreated locally advanced cervical cancer. Monoclonal antibodies, such as nimotuzumab, a humanized anti-epidermal growth factor receptor (EGFR) monoclonal antibody that is approved in many countries for the treatment of EGFR-positive cancers. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Nimotuzumab also stop the growth of cervical cancer by increasing the effect of chemotherapy. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving nimotuzumab together with radiation therapy and cisplatin may kill more tumor cells.

Study of Nimotuzumab Combined With Concurrent Chemoradiotherapy for Locally Advanced Cervical Cancer

Efficacy and Safety of Nimotuzumab Combined With Radiotherapy and Concurrently Cisplatin in Patients With Stage IIB-IVA Cervical Squamous Cell Carcinoma

The rate of patient without progress disease in 3 years after treatment

The rate of patient alive in 3 years after treatment

The rate of patient without recurrence in 3 years after treatment

The rate of patient without metastatic disease in 3 years after treatment

the percentage of patients who experienced complete or partial cancer shrinkage or disappearance after treatment.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
IRX-2 Regimen in Treating Women With Cervical Squamous Intraepithelial Neoplasia 3 or Squamous Vulvar Intraepithelial Neoplasia 3	NCT03267680	Cervical Squamo... Vulvar High Gra...	Cyclophosphamid... Indomethacin IRX-2 Laboratory Biom... Multivitamin Omeprazole Placebo Therapeutic Con...	25 Years -	University of Southern California
Pembrolizumab for the Treatment of Cervical Intraepithelial Neoplasia	NCT04712851	Cervical Intrae... Cervical Squamo... Cervical Squamo...	Pembrolizumab	21 Years -	Jonsson Comprehensive Cancer Center
IRX-2 Regimen in Treating Women With Cervical Squamous Intraepithelial Neoplasia 3 or Squamous Vulvar Intraepithelial Neoplasia 3	NCT03267680	Cervical Squamo... Vulvar High Gra...	Cyclophosphamid... Indomethacin IRX-2 Laboratory Biom... Multivitamin Omeprazole Placebo Therapeutic Con...	25 Years -	University of Southern California
Study of Nimotuzumab Combined With Concurrent Chemoradiotherapy for Locally Advanced Cervical Cancer	NCT03469531	Neoplasms Cervical Adenos... Cervical Squamo... Stage IB Cervic... Stage IIA Cervi... Stage IIB Cervi... Stage III Cervi... Stage IVA Cervi...	Nimotuzumab Cisplatin external-beam r... brachytherapy	18 Years - 75 Years	Zhujiang Hospital

Spots Global Cancer Trial Database for cervical squamous cell carcinoma in situ