Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Recurrence

Carcinoma

Adenocarcinoma

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Disease Progression

Cystadenocarcinoma, Serous

Fallopian Tube Neoplasms

Endometrial Neoplasms

Cystadenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Genital Neoplasms, Female

Urogenital Neoplasms

Fallopian Tube Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Uterine Neoplasms

Uterine Diseases

Endocrine Gland Neoplasms

Ovarian Diseases

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Cystic, Mucinous, and Serous

Ovarian Cancer

Ovarian Epithelial Cancer

Fallopian Tube Cancer

Adenocarcinoma of the Appendix

Antineoplastic Agents

All Drugs and Chemicals

Niraparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Patients receive niraparib PO daily on days 1-28 and copanlisib IV on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Copanlisib

Shannon N Westin

This phase Ib trial studies the best dose and side effects of niraparib and copanlisib in treating patients with endometrial, ovarian, primary peritoneal, or fallopian tube cancer that has come back. Niraparib and copanlisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To determine the maximally tolerated dose (MTD) and recommended phase II dose (RP2D) of the combination of niraparib and copanlisib in patients with recurrent high-grade serous or BRCA mutant ovarian cancer or recurrent endometrial, fallopian tube, or primary peritoneal cancer.

SECONDARY OBJECTIVES:

I. To determine the tolerability of the RP2D of niraparib and copanlisib. II. To determine the safety and observed toxicities of the combination of niraparib and copanlisib in patients with recurrent endometrial, recurrent high-grade serous ovarian, or BRCA mutant ovarian cancer.

III. To estimate the activity of the drug combination at all dose levels in each patient cohort by objective response rate and proportion of patients surviving progression free (PFS) at 6 months.

IV. To determine response duration of the drug combination at all dose levels. V. To determine the pharmacokinetics (PK) of the combination to assess the presence of any drug interaction between the two co-administered agents.

EXPLORATORY OBJECTIVES:

I. To determine if response to therapy is associated with molecular profile of the tumor (including, but not limited to, molecular aberrations in the PI3K-AKT-mTOR pathway or defects in homologous recombination) before treatment.

II. To examine associations with early changes in functional proteomic biomarkers in tumor biopsies before and after treatment and tumor response in patients with recurrent endometrial, recurrent high-grade serous ovarian, or BRCA mutant ovarian cancer treated with the investigational agents.

OUTLINE: This is a dose-escalation study.

Patients receive niraparib orally (PO) daily on days 1-28 and copanlisib intravenously (IV) over 1 hour on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 and 90 days, then every 3 months for up to 5 years.

Niraparib and Copanlisib in Treating Patients With Recurrent Endometrial, Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

A Phase Ib Study of the Oral PARP Inhibitor Niraparib With the Intravenous PI3K Inhibitor Copanlisib for Recurrent Endometrial and Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

Defined as the highest dose for which the posterior probability of toxicity is closest to 30%. Will employ the Bayesian optimal interval design. We will report the posterior probability of dose limiting toxicities (DLT) for each dose level and a 90% credible interval for the probability of DLT at each dose level.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Diseases and Abnormalities at or Before Birth

Skin and Connective Tissue Diseases

Syndrome

Hereditary Breast and Ovarian Cancer Syndrome

Breast Neoplasms

Neoplastic Syndromes, Hereditary

Genetic Diseases, Inborn

Breast Diseases

Skin Diseases

Laboratory Biomarker Analysis

Oophorectomy

Quality-of-Life Assessment

Salpingectomy

Salpingo-Oophorectomy

Karen H Lu

This phase II trial studies how well surgery works in preventing ovarian cancer in patients with genetic mutations at risk of ovarian cancer. Risk reducing salpingo oophorectomy (RRSO) is surgery to remove the fallopian tubes and ovaries at the same time. Interval salpingectomy with delayed oophorectomy (ISDO) is surgery to remove the fallopian tubes. It is not known whether ISDO works better than RRSO at lowering risk of ovarian cancer and improving the sexual function and psychosocial well-being in patients with genetic mutation.

PRIMARY OBJECTIVES:

I. To examine changes in female sexual function with the strategy of interval salpingectomy and delayed oophorectomy (ISDO) compared to the strategy of risk-reducing salpingo-oophorectomy (RRSO) for patients who carry genetic mutations that predispose them to ovarian cancer.

SECONDARY OBJECTIVES:

I. To estimate the onset and severity of menopausal symptoms with ISDO compared to RRSO.

II. To estimate quality of life with ISDO compared to RRSO. III. To examine participants' satisfaction level and cancer worry level with their choice of prophylactic procedures.

IV. To estimate the impact of ISDO compared to RRSO on mental health, including depression, anxiety, and sleep quality.

V. To determine the compliance with ISDO compared to RRSO. VI. To estimate the number of fallopian tube, ovarian, or primary peritoneal malignancies and other malignancies over the course of the study.

OUTLINE: Patients are assigned to 1 of 2 arms.

ARM I: Patients undergo ISDO.

ARM II: Patients undergo RRSO.

After completion of study treatment, patients are followed up at 1 and 6 months, 1 year, and 2 years.

Surgery in Preventing Ovarian Cancer in Patients With Genetic Mutations

WISP (Women Choosing Surgical Prevention)

Will be calculated using the Cochran-Mantel-Haenszel test stratified by age, with 5-year age groups. We will use propensity score methods to account for potential differences between interval salpingectomy with delayed oophorectomy (ISDO) and risk-reducing bilateral salpingectomy with oophorectomy (RRSO) arms with respect to age, baseline survey scores, and other potential confounders, and we will use the propensity scores as inverse weights in logistic regression to model the logit of the probability of having a clinically meaningful change in FSFI score from baseline to 6 months as our primary analysis.

Digestive System Diseases

Pancreatic Neoplasms

Chromosomal Instability

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Pancreatic Cancer

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Participants receive pembrolizumab IV over 30 minutes on day 1 and epacadostat PO BID on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unaccepted toxicity.

Epacadostat

Milind Javle

This phase II trial studies how well epacadostat and pembrolizumab work in treating participants with pancreatic cancer that has spread to other places in the body. Epacadostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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. Giving epacadostat and pembrolizumab may work better in treating participants with pancreatic cancer.

PRIMARY OBJECTIVES:

I. To determine the efficacy of epacadostat in combination with pembrolizumab as determined by the best overall response rate in previously treated patients with advanced pancreatic adenocarcinoma with homologous recombination repair deficiency (HRD) aberrations.

SECONDARY OBJECTIVES:

I. To further determine the efficacy of epacadostat in combination with pembrolizumab in previously treated patients with advanced pancreatic adenocarcinoma with HRD aberrations.

II. To assess the safety and tolerability of epacadostat in combination with pembrolizumab in previously treated patients with advanced pancreatic adenocarcinoma with HRD aberrations.

EXPLORATORY OBJECTIVES:

I. To identify predictive, mechanistic, and/or surrogate biomarkers of clinical efficacy of epacadostat in combination with pembrolizumab in previously treated patients with advanced pancreatic adenocarcinoma with HRD aberrations utilizing exploratory studies investigating the patients tumor and immune system response including: flow cytometry of fresh peripheral blood mononuclear cell (PBMC), PDL-1.

OUTLINE:

Participants receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and epacadostat orally (PO) twice daily (BID) on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unaccepted toxicity.

After completion of study treatment, participants are followed up at 30 days, every 8 weeks for 3 years, and then every 12 weeks thereafter.

Epacadostat and Pembrolizumab in Treating Participants With Advanced Pancreatic Cancer

Single-Arm, Phase II Proof of Concept Study of IDO-1 Inhibitor Epacadostat in Combination With Pembrolizumab in Advanced Pancreatic Cancer With Chromosomal Instability/Homologous Recombination Repair Deficiency (HRD)

The objective response rate (partial response \[PR\] + complete response \[CR\]) and its corresponding exact 1-sided 90% confidence interval (CI) will be estimated.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Niraparib and Copanlisib in Treating Patients With Recurrent Endometrial, Ovarian, Primary Peritoneal, or Fallopian Tube Cancer	NCT03586661	Deleterious BRC... Deleterious BRC... Endometrial Ade... High Grade Ovar... Platinum-Resist... Primary Periton... Progressive Dis... Recurrent Endom... Recurrent Fallo... Recurrent Ovari... Recurrent Prima...	Copanlisib Niraparib	18 Years -	M.D. Anderson Cancer Center
Surgery in Preventing Ovarian Cancer in Patients With Genetic Mutations	NCT02760849	Deleterious BAR... Deleterious BRC... Deleterious BRC... Deleterious BRI... Deleterious EPC... Deleterious MLH... Deleterious MSH... Deleterious MSH... Deleterious PAL... Deleterious PMS... Deleterious RAD... Deleterious RAD... Hereditary Brea... Premenopausal	Laboratory Biom... Oophorectomy Quality-of-Life... Salpingectomy Salpingo-Oophor...	30 Years - 50 Years	M.D. Anderson Cancer Center
Surgery in Preventing Ovarian Cancer in Patients With Genetic Mutations	NCT02760849	Deleterious BAR... Deleterious BRC... Deleterious BRC... Deleterious BRI... Deleterious EPC... Deleterious MLH... Deleterious MSH... Deleterious MSH... Deleterious PAL... Deleterious PMS... Deleterious RAD... Deleterious RAD... Hereditary Brea... Premenopausal	Laboratory Biom... Oophorectomy Quality-of-Life... Salpingectomy Salpingo-Oophor...	30 Years - 50 Years	M.D. Anderson Cancer Center
Epacadostat and Pembrolizumab in Treating Participants With Advanced Pancreatic Cancer	NCT03432676	ATM Gene Mutati... Deleterious BRC... Deleterious BRC... Homologous Reco... Pancreatic Duct... Stage II Pancre... Stage IIA Pancr... Stage IIB Pancr... Stage III Pancr... Stage IV Pancre...	Epacadostat Pembrolizumab	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for deleterious brca1 gene mutation