Neoplasms

All Conditions

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma

Recurrence

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Uterine Cervical Neoplasms

Vaginal Neoplasms

Vulvar Neoplasms

Endometrial Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Uterine Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Vulvar Diseases

Vaginal Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Vaginal Cancer

Vulvar Cancer

All Drugs and Chemicals

Antineoplastic Agents

Immunomodulating Agents

Durvalumab

Tremelimumab

Antineoplastic Agents, Immunological

A modified 3+3 design will be used in this trial Lead-in phase with Durvalumab\* and radiation therapy

\*q4 weeks durvalumab for 13 cycles or until progression

* Durvalumab
* Tremelimumab\* -- Start radiation dose from safety lead-in (level 0 or level -1) \*q4 weeks durvalumab / tremelimumab for 4 cycles and continue durvalumab for 13 cycles or until disease progression

Durvalumab is given by intravenous infusion every 4 weeks for a maximum of 13 doses over 52 weeks. One cycle is defined as every 4 weeks. Each infusion will take approximately 1 hour.

Tremelimumab is given by intravenous infusion every 4 weeks for a maximum of 4 doses over 16 weeks. One cycle is defined as every 4 weeks. If receiving both durvalumab and tremelimumab for the first 4 cycles, they will be given on the same day. Each infusion will take approximately 1 hour

Radiation treatment will begin on the same day as the first immunotherapy infusion or on the following day. The radiation treatment course is either 1 day or 5 days.

Radiation Therapy

Martin King, MD, PhD

This research study is evaluating the safety and effectiveness of 2 immunotherapy drugs in combination with radiation therapy as a possible treatment for recurrent or metastatic gynecologic cancer.

The names of the immunotherapy drugs involved in this study are:

* Durvalumab
* Tremelimumab

This research study is a Phase I clinical trial, which tests the safety of an investigational drug or drugs and also tries to define the appropriate dose and combination of the investigational drugs to use for further studies. "Investigational" means that the drugs are being studied but have not been approved by the FDA (the U.S. Food and Drug Administration).

In this study, the combination of durvalumab and tremelimumab is considered to be investigational and as such has not been approved for this or any cancer.

-- Durvalumab and tremelimumab are immunotherapy drugs that may stop cancer cells from growing by activating the immune system. The immune system is one of the body's natural defenses against the growth of cancer cells. AstraZeneca has evaluated the effectiveness and side effects of both durvalumab and tremelimumab individually for many cancer types, including lung, head and neck cancer, and melanoma. These types of immunotherapy drugs are also being studied in ovarian, endometrial and cervical cancer. In addition, AstraZeneca has studied the combination of durvalumab and tremelimumab in participants with lung and pancreatic cancers. Based on these studies, AstraZeneca has determined the dosing, schedule and expected side effects for the 2 study drugs when delivered together.

In women with recurrent or metastatic gynecologic cancer, radiation therapy is often used to help with symptoms, such as bleeding, pain or swelling. Clinical reports have shown that radiation treatment can increase the body's response to an immunotherapy drug against tumors both within and outside the radiation field. This study is the first in which the combination of durvalumab, tremelimumab and abdominal or pelvic radiation is given to humans. The investigators hope that this combination with radiation will lead to a better treatment response to the immunotherapy drugs.

The investigators will also look to see if participants whose tumors contain a particular genetic make-up have a better response to immunotherapy and radiation treatment.

Durvalumab, Tremelimumab + Radiotherapy in Gynecologic Cancer

A Phase 1 Study of Durvalumab, Tremelimumab and Radiotherapy in Recurrent Gynecologic Cancer

Incidence of dose-limiting toxicities for each dose level or regimen

Response rate within the radiation field by RECIST and irRC criteria

Tumor control within the radiation field by RECIST and irRC criteria

Abscopal response rate for measurable disease outside the radiation field by RECIST and irRC criteria

Time from overall response by RECIST or irRC until time of recurrent or progressive disease

Spots Global Cancer Trial Database for metastatic vulvar cancer