Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

All Conditions

Digestive System Diseases

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma

Fallopian Tube Neoplasms

Peritoneal Neoplasms

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

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Fallopian Tube Diseases

Abdominal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Peritoneal Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Fallopian Tube Cancer

All Drugs and Chemicals

Vaccines

Patients receive the alpha-type-1 polarized dendritic cell vaccine ID 2 weeks before day 0, on day 0, and on day 28. Patients also receive aDC1 IP over 3-10 seconds on day 0. In the absence of unacceptable side effects, patients may receive the alpha-type-1 polarized dendritic cell vaccine every 1-3 months at the discretion of the physician.

Alpha-type-1 Polarized Dendritic Cells

Autologous Natural Killer Cell-like CTLs

Emese Zsiros, MD, PhD

This phase I/IIa trial studies the side effects and best dose of a type of specialized immune cell (natural killer cell-like cytotoxic T-lymphocytes (CTLs) (nCTLs) and how well they work when given with a vaccine (alpha-type-1 polarized dendritic cells) in treating patients with stage II-IV ovarian, fallopian tube, or primary peritoneal cancer. nCTLs are immune cells that are isolated from each patient?s blood and "taught" in the laboratory how to recognize and eliminate tumor cells. These "educated" immune cells are then given back to the patient. An alpha-type-1 polarized dendritic cell vaccine is another population of "educated" immune cells that work to support the infused nCTLs. Giving nCTLS with a dendritic cell vaccine may work better in treating patients with ovarian, fallopian tube, or primary peritoneal cancer.

PRIMARY OBJECTIVES I. To evaluate the safety, tolerability, and feasibility of intraperitoneal (i.p.) administration of autologous tumor loaded DC vaccines (alpha-type-1 polarized dendritic cell \[alphaDC1\]) combined with intradermally administered aDC1 .(Safety \[Phase I aspect\]) II. To measure the intraperitoneal induction and persistence of aDCI induced sensitized cytotoxic T Cells (CTLs), which express natural killer (NK) cell-like features (nCTLs) and total CTLs following intraperitoneal administration of aDC1. (Local Immunologic Efficacy \[Phase II aspect\])

SECONDARY OBJECTIVES I. To study the T cell populations generated that correlates with higher anti-tumor responses.

EXPLORATORY OBJECTIVES I. To evaluate the progression-free survival and overall survival of patients treated with this regimen.

OUTLINE: This is a phase I, dose-escalation study of nCTLs, followed by a phase IIa study.

Patients receive the alpha-type-1 polarized dendritic cell vaccine intradermally (ID) 2 weeks before day 0, on day 0, and on day 28. Patients also receive nCTLs intraperitoneally (IP) over 15-30 minutes on day 0. In the absence of unacceptable side effects, patients may receive the alpha-type-1 polarized dendritic cell vaccine every 1-3 months at the discretion of the physician.

After completion of study treatment, patients are followed up at 14 days, then at 6 and 12 months.

Specialized Immune Cells (nCTLs) and a Vaccine (Alpha-type-1 Polarized Dendritic Cells) in Treating Patients With Stage II-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

A Phase I/IIa Safety and Immunologic Efficacy Trial of Intraperitoneal Induction of CTLs Combined With Alpha-Dendritic Cell Vaccine for Primary Ovarian Cancer

Will examine time-to-disease progression graphically via the generation of Kaplan-Meier survival curves.

Will be used in the estimation of the maximum tolerated dose (MTD) and the accompanying of the dose escalation decisions. However, no formal analyses of DLTs are planned.

Change in immune response will be measured by the increase in the number of CD3+CD8+NKG2D (high) natural killer cell-like cytotoxic T-lymphocyte (CTLs) (nCTLs) and the increase in total CD3+CD8+ CTLs recovered in the peritoneal washes with evaluation on day 0 versus day 2. The analysis will consist of an analysis-of-covariance (ANCOVA) for the outcome of post-pre ACT treatment cell count with a factor for dose and sampling time 48 hrs +/- 24 hrs.

At day 0 will obtain peritoneal material (outflow and washes) directly before i.p. infusion of nCTLs, as well as day 2 (48 hours +/- 24 hours), day 7 (+/- 2 days), 2 weeks (14 days +/- 2 days) and 4 weeks (28 days +/- 3 days) later.

Will estimate the half-life of CD3/CD8/NKG2D (triple-positive nCTLs) cell counts and longitudinal changes CD3/CD8 cell counts (double-positive CTLs, which include both nCTLs and additional CTLs newly recruited CTLs from the circulation) cell counts as a function of dose and time. A nonlinear regression model with a random effect for subject (population pharmacokinetics \[PK\]) will be fit to a one-compartment kinetics first-order absorption model per dose level.

National Cancer Institute (NCI)

Roswell Park Cancer Institute

Adenocarcinoma

Cystadenocarcinoma, Serous

Cystadenocarcinoma

Neoplasms, Cystic, Mucinous, and Serous

Adenocarcinoma of the Appendix

Antineoplastic Agents

Paclitaxel

Carboplatin

Letrozole

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Aromatase Inhibitors

Enzyme Inhibitors

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Patients receive paclitaxel IV over 3 hours and carboplatin IV on day 1. Cycles repeat every 21 days for up to 6 cycles. Patients then receive letrozole PO QD in the absence of disease progression or unacceptable toxicity. Patients undergo blood collection and tumor biopsy during screening as well as medical imaging throughout the study.

Patients receive letrozole PO QD. Cycles repeat every 21 days for up to 6 cycles. Patients then receive letrozole orally PO QD in the absence of disease progression or unacceptable toxicity as maintenance therapy. Patients undergo blood collection and tumor biopsy during screening as well as medical imaging throughout the study.

Biopsy

Biospecimen Collection

Imaging Technique

Site Public Contact

Nitya Alluri

Nicholas DiBella

John H. Farley

John A. Ellerton

Shahzad Siddique

Setsuko K. Chambers

Jay W. Carlson

David B. Engle

Heather R. Williams

Ramey D. Littell

Deepti Behl

Mihae Song

Yevgeniya J. Ioffe

Lee-May Chen

Amanda N Fader

This phase III trial studies how well letrozole with or without paclitaxel and carboplatin works in treating patients with stage II-IV low-grade serous carcinoma of the ovary, fallopian tube, or peritoneum. Letrozole is an enzyme inhibitor that lowers the amount of estrogen made by the body which in turn may stop the growth of tumor cells that need estrogen to grow. Drugs used in chemotherapy, such as paclitaxel and carboplatin, 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. It is not yet known whether giving letrozole alone or in combination with paclitaxel and carboplatin works better in treating patients with low-grade serous carcinoma of the ovary, fallopian tube, or peritoneum compared to paclitaxel and carboplatin without letrozole.

PRIMARY OBJECTIVE:

I. To examine if letrozole monotherapy/maintenance (L/L) is non-inferior to intravenous (IV) paclitaxel/carboplatin and maintenance letrozole (CT/L) with respect to progression-free survival (PFS) in women with stage II-IV primary low-grade serous carcinoma of the ovary or peritoneum after primary surgical cytoreduction.

SECONDARY OBJECTIVES:

I. To compare the nature, frequency and maximum degree of toxicity as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 for each treatment arm.

II. To compare the relative frequency of objective tumor response in those with measurable disease after cytoreductive surgery for each treatment arm.

III. To compare overall survival for each treatment arm. IV. To compare the CT/L and L/L arms with respect to patients' adherence to letrozole therapy as measured by pill counts.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive paclitaxel IV over 3 hours and carboplatin IV on day 1. Cycles repeat every 21 days for up to 6 cycles. Patients then receive letrozole orally (PO) once daily (QD) in the absence of disease progression or unacceptable toxicity. Patients undergo blood collection and tumor biopsy during screening as well as medical imaging throughout the study.

ARM II: Patients receive letrozole PO QD. Cycles repeat every 21 days for up to 6 cycles. Patients then receive letrozole orally PO QD in the absence of disease progression or unacceptable toxicity as maintenance therapy. Patients undergo blood collection and tumor biopsy during screening as well as medical imaging throughout the study.

After completion of study treatment/intervention, patients/participants are followed up every 3 months for 1 year, then every 6 months for 3 years, then annually thereafter.

Letrozole With or Without Paclitaxel and Carboplatin in Treating Patients With Stage II-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

A Randomized Phase III, Two-Arm Trial of Paclitaxel/Carboplatin/Maintenance Letrozole Versus Letrozole Monotherapy in Patients With Stage II-IV, Primary Low-Grade Serous Carcinoma of the Ovary or Peritoneum

The PFS comparison will be assessed at the second interim and final analyses using a logrank test stratified by country and residual disease status. Estimates for the letrozole/letrozole (L/L) vs paclitaxel/carboplatin/letrozole (CT/L) hazard ratio and its confidence interval will be obtained using a stratified Cox proportional hazards model. Potential confounding factors, including the stratification factors, performance status and self-declared racial designation will be considered in a final exploratory model. A forest plot of treatment hazard ratios with confidence intervals within subgroups will also be reported. PFS will be characterized by treatment group with Kaplan-Meier plots and estimates of the median PFS.

The nature, frequency and degree of toxicity will be tabulated at the System Organ Class and AE Term levels using Common Terminology Criteria for Adverse Events version 5.0. Each patient will be represented according the maximum grade observed for each term, within randomized treatment assignment. Tabulations will show the number and percentage of patients by maximum grade, within their randomized treatment assignment.

Will be estimated as the binomial proportion of patients with best overall response of complete response (CR) or partial response (PR) among patients with measurable disease after cytoreductive surgery. Response rates and their 95% Wilson-Score confidence intervals will be estimated for each treatment arm, using the randomized treatment assignment. The odds-ratio for ORR in the L/L vs CT/L arms will be estimated from the multivariable logistic regression model adjusted for stratification factors.

Will be defined among patients with best overall response of CR or PR. Comparison of response duration between the randomized treatment arms will be supported by Kaplan Meier methods, and the corresponding estimates for median duration and its 95% confidence intervals.

Differences in OS across the randomized treatment groups will be assessed using Kaplan Meier methods, with median time to death estimates and the corresponding 95% confidence intervals. The L/L vs CT/L hazard ratio will be estimated by a proportional hazards model stratified by the randomization stratification factors.

Will be quantified as the mean rate of adherence (MRA), calculated as the proportion of product not returned divided by the number of days since the previous visit at which study products were dispensed. Currently, the letrozole is delivered in a 2.5 mg pill, and the recommended dose is 2.5 mg per day. This outcome will be computed for each treatment cycle (generally 21 days). The mean MRA will be compared between the randomized treatment groups using linear mixed model methods. The model will be specified with a random patient effect, and fixed effects for randomized treatment indicator, time (cycle number) and the interaction, with an adjustment for the protocol stratification factors. Primary interest is in the difference in mean (MRA) at cycles 1, 6 and 12 between the treatment group. The results will be reported as the estimated mean (MRA) and 95% confidence intervals for each treatment/time combination. Treatment differences within stratification factors may also be considered.

NRG Oncology

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Specialized Immune Cells (nCTLs) and a Vaccine (Alpha-type-1 Polarized Dendritic Cells) in Treating Patients With Stage II-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer	NCT03735589	Stage II Fallop... Stage II Ovaria... Stage II Primar... Stage IIA Fallo... Stage IIA Ovari... Stage IIA Prima... Stage IIB Fallo... Stage IIB Ovari... Stage IIB Prima... Stage III Fallo... Stage III Ovari... Stage III Prima... Stage IIIA Fall... Stage IIIA Ovar... Stage IIIA Prim... Stage IIIA1 Fal... Stage IIIA1 Ova... Stage IIIA2 Fal... Stage IIIA2 Ova... Stage IIIB Fall... Stage IIIB Ovar... Stage IIIB Prim... Stage IIIC Fall... Stage IIIC Ovar... Stage IIIC Prim... Stage IV Fallop... Stage IV Ovaria... Stage IV Primar... Stage IVA Fallo... Stage IVA Ovari... Stage IVA Prima... Stage IVB Fallo... Stage IVB Ovari... Stage IVB Prima...	Alpha-type-1 Po... Autologous Natu...	18 Years -	Roswell Park Cancer Institute
Specialized Immune Cells (nCTLs) and a Vaccine (Alpha-type-1 Polarized Dendritic Cells) in Treating Patients With Stage II-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer	NCT03735589	Stage II Fallop... Stage II Ovaria... Stage II Primar... Stage IIA Fallo... Stage IIA Ovari... Stage IIA Prima... Stage IIB Fallo... Stage IIB Ovari... Stage IIB Prima... Stage III Fallo... Stage III Ovari... Stage III Prima... Stage IIIA Fall... Stage IIIA Ovar... Stage IIIA Prim... Stage IIIA1 Fal... Stage IIIA1 Ova... Stage IIIA2 Fal... Stage IIIA2 Ova... Stage IIIB Fall... Stage IIIB Ovar... Stage IIIB Prim... Stage IIIC Fall... Stage IIIC Ovar... Stage IIIC Prim... Stage IV Fallop... Stage IV Ovaria... Stage IV Primar... Stage IVA Fallo... Stage IVA Ovari... Stage IVA Prima... Stage IVB Fallo... Stage IVB Ovari... Stage IVB Prima...	Alpha-type-1 Po... Autologous Natu...	18 Years -	Roswell Park Cancer Institute
Letrozole With or Without Paclitaxel and Carboplatin in Treating Patients With Stage II-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer	NCT04095364	Low Grade Fallo... Ovarian Low Gra... Primary Periton... Stage II Fallop... Stage II Ovaria... Stage II Primar... Stage III Fallo... Stage III Ovari... Stage III Prima... Stage IV Fallop... Stage IV Ovaria... Stage IV Primar...	Biopsy Biospecimen Col... Carboplatin Imaging Techniq... Letrozole Paclitaxel	18 Years -	NRG Oncology

Spots Global Cancer Trial Database for stage ii primary peritoneal cancer ajcc v8