Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Recurrence

Endometrial Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Antineoplastic Agents

All Drugs and Chemicals

Doxorubicin

Liposomal doxorubicin

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Doxorubicin 60 mg/kg IV over 30 minutes on day 1 every 3 weeks up to 9 cycles in combination with Pembrolizumab (MK-3475) 200 mg IV Q3W

pembrolizumab in combination with doxorubicin

This is a non-randomized, single arm, multi-center, phase II study of pembrolizumab in combination with doxorubicin in subjects with recurrent/metastatic endometrial cancer.

Non-randomized, single arm, multi-center, phase II study

Pembrolizumab in Combination With Doxorubicin in Advanced, Recurrent or Metastatic Endometrial Cancer

Phase II Trial of Pembrolizumab in Combination With Doxorubicin in Advanced, Recurrent or Metastatic Endometrial Cancer (TOPIC)

To evaluate the efficacy of anti-PD1 blockade with pembrolizumab in combination with immunogenic chemotherapy with doxorubicin in patients with recurrent endometrial cancer in terms of patients who survived progression free (PFS) at least 6 months.

PFS, defined as the time from allocation to the first documented disease progression according to RECIST 1.1 or death due to any cause, whichever occurs first. ORR will be used as the primary endpoint per RECIST 1.1 criteria, as assessed by investigators.

Vall d'Hebron Institute of Oncology

Skin and Connective Tissue Diseases

Gland and Hormone Related Diseases

Rare Diseases

Uterine Cervical Neoplasms

Breast Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Endocrine System Diseases

Gonadal Disorders

Uterine Cervical Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Patients treated with at least one dose - 852A subcutaneous injection.

Patients who received all 24 doses of 852A per protocol.

0.2% 852a subcutaneous injection, 2 times per week for 12 weeks (24 doses) starting at 0.6 mg/m2; subsequent dose escalation for additional courses may be increased by 0.2 mg/m2 not to exceed 1.2 mg/m2.

852A

Sarah Cooley, MD

Melissa A. Geller, MD

The purpose of this study is to evaluate the anti-tumor activity of 852A when used to treat metastatic breast, ovarian, endometrial or cervical cancer not responding to standard treatment.

852A will be administered as a subcutaneous injection (SC) 2 times per week for 12 weeks (24 doses) with provisions for dose escalation or reduction based on tolerability.

Study of Immune Response Modifier in the Treatment of Breast, Ovarian, Endometrial and Cervical Cancers

Phase II Study of 852A Administered Subcutaneously in Patients With Metastatic Refractory Breast, Ovarian, Endometrial and Cervical Cancers

Assessment of anti-tumor activity of 852A using Response Evaluation Criteria in Solid Tumors (RECIST) criteria to evaluate tumor response after 24 doses. Complete Response (CR)= disappearance of all target lesions, Partial Response (PR) = at least 30% decrease in sum of longest diameter of target lesions, Progressive Disease (PD) = at least 25% increase in sum of longest diameter of target lesions, Stable Disease = neither PR or PD.

Measures the difference of IL1ra (cytokine) values as a means of immune activation pre-treatment and 6 hours post-treatment in patients that received at least one dose of study treatment with 852A.

Measures differences in IP-10 (cytokine) values as a means of immune activation pre-treatment and 6 hours post-treatment in patients that received at least one dose of study treatment with 852A.

Measures difference in MIP-1a (cytokine) values as a means of immune activation pre-treatment and 6 hours post-treatment in patients that received at least one dose of study treatment with 852A.

Measures difference in Macrophage Inflammatory Protein-1 Beta (cytokine) values as a means of immune activation pre-treatment and 6 hours post-treatment in patients that received at least one dose of study treatment with 852A.

Measures difference in Soluble CD40 ligand (cytokine) values as a means of immune activation pre-treatment and 6 hours post-treatment in patients that received at least one dose of study treatment with 852A.

Measures difference in Tumor necrosis factor-alpha (cytokine) values as a means of immune activation pre-treatment and 6 hours post-treatment in patients that received at least one dose of study treatment with 852A.

Pfizer

Masonic Cancer Center, University of Minnesota

Melissa Geller, M.D.

Safety (toxicity) is one of the objectives of this study. Only serious adverse events were reported and collected as part of this study.

Patients that received at least one dose of study treatment with 852A (0.6 mg/m\^2 to 1.2 mg/m\^2 dose, 2 times/week for 12 weeks).

Patients Treated With 852A Study Drug

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Other Adverse Events that occurred were noted as targeted toxicities and not captured as adverse events.

Complete Response

Partial Response

Stable Disease

Progressive Disease

Participants with ovarian cancer who received all 24 doses of 852A.

Patients With Ovarian Cancer

Includes only patients that received all 24 doses of 852A.

Patients With Tumor Response (Response Evaluation Criteria in Solid Tumors) Who Received All 24 Doses of 852A.

Difference in range values from pre-treatment to post-treatment for cytokine level of IL1ra in patients treated with 852A.

Patients Treated With 852A

One patient did not have value reported at 6 hours after treatment, so cannot be included.

Mean Difference Values for Interleukin 1 Receptor Antagonist (IKL1ra)

Difference in range values from pre-treatment to post-treatment for cytokine level of IP-10 in patients treated with 852A.

One patient did not have a value reported at 6 hours after treatment so cannot be included in analysis.

Mean Difference Values for 10 kDa Interferon-gamma-induced Protein (IP-10)

Difference in range values from pre-treatment to post-treatment for Macrophage Inflammatory Protein-1 Alpha (cytokine) level in patients treated with 852A.

Only 5 patients had a value reported at 6 hours after treatment.

Mean Difference Values for Macrophage Inflammatory Protein-1 Alpha (MIP-1a)

Difference in range values from pre-treatment to post-treatment for cytokine level of MIP-1b in patients treated with 852A.

Two patients did not have recorded values at 6 hours after treatment so cannot be included in analysis.

Mean Difference Values for Macrophage Inflammatory Protein-1 Beta (MIP-1b)

Difference in range values from pre-treatment to post-treatment for cytokine level of sCD40L in patients treated with 852A.

One patient did not have recorded value at 6 hours after treatment and cannot be included in analysis.

Mean Difference Values for Soluble CD40 Ligand (sCD40L)

Difference in range values from pre-treatment to post-treatment for cytokine level of TNF-a in patients treated with 852A.

Only 9 patients had recorded values at 6 hours after treatment and were included in analysis.

Mean Difference Values for Tumor Necrosis Factor-alpha (TNF-a)

Overall Study

Carcinoma

Vaginal Neoplasms

Vulvar Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Vulvar Diseases

Vaginal Diseases

Vaginal Cancer

Vulvar Cancer

Immunomodulating Agents

Durvalumab

Tremelimumab

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

From start of treatment to time of progression or death

From start of treatment until death due to any cause

AstraZeneca

Dana-Farber Cancer Institute

Principal Investigator

Digestive System Diseases

Diseases and Abnormalities at or Before Birth

Nutritional and Metabolic Diseases

Adenocarcinoma

Syndrome

Carcinosarcoma

Mixed Tumor, Mullerian

Adenocarcinoma, Clear Cell

Colorectal Neoplasms

Colorectal Neoplasms, Hereditary Nonpolyposis

Adenoma, Pleomorphic

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Neoplastic Syndromes, Hereditary

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Genetic Diseases, Inborn

DNA Repair-Deficiency Disorders

Metabolic Diseases

Sarcoma

Neoplasms, Connective and Soft Tissue

Turcot Syndrome

Malignant Mixed Mullerian Tumor

Uterine Carcinosarcoma

Soft Tissue Sarcoma

Paclitaxel

Carboplatin

Tislelizumab

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Chemo naïve patients receive tislelizumab IV over 30-60 minutes on day 1. Cycles repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity. Beginning cycle 4, patients who are chemotherapy naive with progressive disease, stable disease, or partial response, also receive carboplatin IV and paclitaxel IV every 21 days per standard of care for 6-9 cycles at the discretion of the treating physician.

Patients who have received prior chemotherapy will receive single agent tislelizumab IV over 30-60 minutes on day 1. Cycles repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.

Biopsy

Floor Backes, MD

This clinical trial evaluates the effect of tislelizumab in treating patients with mismatch repair deficient endometrial cancer that has come back (recurrent). Deoxyribonucleic acid (DNA) mismatch repair (MMR) is a system for recognizing and repairing DNA errors and damage. Mismatch repair deficient tumors (dMMR) may have difficulty repairing DNA mutations during replication that may affect tumor's response to therapy. Immunotherapy with monoclonal antibodies, such as tislelizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving tislelizumab may help treat patients with mismatch repair deficient endometrial cancer.

PRIMARY OBJECTIVE:

I. To evaluate the effect of tislelizumab (BGB-A317) on the diversity and dynamics of the T cell receptor repertoire in responders versus non-responders.

SECONDARY OBJECTIVES:

I. To evaluate the effect of tislelizumab on tumor mutational profiles between responders and non-responders.

II. To evaluate the effect of tislelizumab +/- carboplatin/paclitaxel on PD-1/PD-L1 expression and other immune markers in tumor biopsies between responders and non-responders.

III. To evaluate the safety and tolerability of tislelizumab +/- carboplatin/paclitaxel in patients with MMR deficient recurrent endometrial cancer.

EXPLORATORY OBJECTIVES:

I. To explore the effect of adding carboplatin/paclitaxel to tislelizumab on tumor mutational profiles.

II. To explore the effect of adding carboplatin/paclitaxel to tislelizumab (BGB-A317) on the diversity and dynamics of the T cell receptor repertoire.

III. To explore the objective antitumor activity (complete and partial response) of tislelizumab as measured by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 criteria.

IV. To explore the objective antitumor activity (complete and partial response) of tislelizumab/carboplatin/paclitaxel after single agent tislelizumab as measured by RECIST v1.1 criteria V. To explore the progression free survival in patients with mismatch repair deficiency (dMMR) recurrent endometrial cancer treated with tislelizumab +/- carboplatin/paclitaxel.

OUTLINE:

Patients receive tislelizumab intravenously (IV) over 30-60 minutes on day 1. Cycles repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity. Beginning cycle 4, patients who are chemotherapy naive with progressive disease, stable disease, or partial response, also receive carboplatin IV and paclitaxel IV every 21 days per standard of care for 6-9 cycles at the discretion of the treating physician.

After completion of study treatment, patients are followed up at 30, 60, and 90 days, and then periodically thereafter.

Tislelizumab for the Treatment of Recurrent Mismatch Repair Deficient Endometrial Cancer

Pilot Study of Tislelizumab (BGB-A317) in Recurrent Mismatch Repair Deficient Endometrial Cancer and the Effect on the Tumor Microenvironment

1) Measurements of TCRB clonal expansion in peripheral blood. Measurements of TCR in peripheral blood/-tissue

Measurements of TCRB clonal expansion in peripheral blood.

Measurements of TCRB diversity in peripheral blood

Evaluated by Response Evaluation Criteria in Solid Tumors version 1.1.

Floor Backes

Avelumab

Axitinib

Histamine Antagonists

Histamine H1 Antagonists

Talazoparib

Protein Kinase Inhibitors

Enzyme Inhibitors

Poly(ADP-ribose) Polymerase Inhibitors

Participants with Pole mutated endometrial cancer Avelumab will be administered intravenously twice per cycle

Participants with MSS mutated endometrial cancer Avelumab will be administered intravenously twice per cycle

Participants with MSS mutated endometrial cancer Avelumab will be administered intravenously twice per cycle Talazoparib will be administered one time per day by mouth

Participants with MSS mutated endometrial cancer Avelumab will be administered intravenously twice per cycle Axitinib will be administered twice per day by mouth

Avelumab will be administered intravenously twice per cycle Each Cycle lasts 28 days Premedication Antihistamine and Paracetamol will be administered prior to treatment

Talazoparib will be taken one time per day by mouth Each Cycle lasts 28 days

Axitinib will be taken twice per day by mouth Each Cycle lasts 28 days

Panagiotis Konstantinopoulos, MD, PhD

This research study is evaluating a drug called Avelumab alone and in combination with Talazoparib or Axitinib as a possible treatment for recurrent or metastatic endometrial cancer.

This research study is a Phase II clinical trial. Phase II clinical trials test the effectiveness of an investigational drug to learn whether the drug works in treating a specific cancer. "Investigational" means that the drug is still being studied and that research doctors are trying to find out more about it-such as the safest dose to use, the side effects it may cause, and if the drug is effective for treating different types of cancer. It also means that the FDA (the U.S. Food and Drug Administration) has not yet approved the drug for use in patients, including people with Metastatic Endometrial Cancer.

Avelumab is a drug that may stop cancer cells from growing by enabling the activation of the immune system. Avelumab blocks an immune inhibiting signal that can impair the ability of the immune system to attack cancers.

Talazoparib is a drug that stops the activity of a protein (called PARP) that's involved in repairing damage to the DNA within your cells. When PARP is turned off by Talazoparib in cancer cells, DNA damage cannot be repaired and leads to the death of the cancer cells.

Axitinib is a drug that may stop cancer cells from growing by blocking certain proteins that cancer cells use to form new blood vessels, which the cancer needs in order to grow.

In this research study, the investigators are looking to see whether Avelumab, the combination of Avelumab and Talazoparib, or the combination of Avelumab and Axitinib are effective in treating recurrent and Metastatic Endometrial Cancer.

Additionally, the investigators are looking to see if participants whose tumors contain a particular genetic make-up will have better response to Avelumab, the combination of Avelumab and Talazoparib, or the combination of Avelumab and Axitinib.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pembrolizumab in Combination With Doxorubicin in Advanced, Recurrent or Metastatic Endometrial Cancer	NCT03276013	Endometrial Neo...	Pembrolizumab	18 Years -	Vall d'Hebron Institute of Oncology
Study of Immune Response Modifier in the Treatment of Breast, Ovarian, Endometrial and Cervical Cancers	NCT00319748	Breast Cancer Ovarian Cancer Endometrial Can... Cervical Cancer	852A	18 Years -	Masonic Cancer Center, University of Minnesota
Durvalumab, Tremelimumab + Radiotherapy in Gynecologic Cancer	NCT03277482	Recurrent Gynec... Metastatic Cerv... Metastatic Ovar... Metastatic Vagi... Metastatic Vulv... Metastatic Endo... Recurrent Cervi... Recurrent Ovari... Recurrent Vagin... Recurrent Vulva... Recurrent Endom...	Durvalumab Tremelimumab Radiation Thera...	18 Years -	Dana-Farber Cancer Institute
Tislelizumab for the Treatment of Recurrent Mismatch Repair Deficient Endometrial Cancer	NCT04906382	Lynch Syndrome Recurrent Endom... Recurrent Endom... Recurrent Uteri... Mismatch Repair... Recurrent Endom... Metastatic Endo...	Biopsy Carboplatin Paclitaxel Tislelizumab	18 Years -	Ohio State University Comprehensive Cancer Center
Study of Immune Response Modifier in the Treatment of Breast, Ovarian, Endometrial and Cervical Cancers	NCT00319748	Breast Cancer Ovarian Cancer Endometrial Can... Cervical Cancer	852A	18 Years -	Masonic Cancer Center, University of Minnesota
Pembrolizumab in Combination With Doxorubicin in Advanced, Recurrent or Metastatic Endometrial Cancer	NCT03276013	Endometrial Neo...	Pembrolizumab	18 Years -	Vall d'Hebron Institute of Oncology
Avelumab in Patients With MSS, MSI-H and POLE-mutated Recurrent or Persistent Endometrial Cancer and of Avelumab/Talazoparib and Avelumab/Axitinib in Patients With MSS Recurrent or Persistent Endometrial Cancer	NCT02912572	Metastatic Endo...	Avelumab Talazoparib Axitinib	18 Years -	Dana-Farber Cancer Institute

Spots Global Cancer Trial Database for metastatic endometrial cancer