Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Digestive System Diseases

Rare Diseases

Recurrence

Carcinoma

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Fallopian Tube Neoplasms

Peritoneal 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

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

Antineoplastic Agents

Anti-Infective Agents

Analgesics

Amino Acids

Antibodies

Molgramostim

Sargramostim

Aldesleukin

Antibodies, Bispecific

Immunoglobulins

Muromonab-CD3

Interleukin-2

Analgesics, Non-Narcotic

Anti-HIV Agents

Anti-Retroviral Agents

Antiviral Agents

Immunologic Factors

Serine

Patients receive HER2Bi-aATC IV over 5-15 minutes and IP within 3-4 days of IV dose weekly for 4 weeks. Patients also receive low-dose aldesleukin SC daily and sargramostim SC twice weekly beginning 3 days before the first HER2Bi-aATC infusions infusion and ending 7 days after the last HER2Bi-aATC infusion. Treatment continues in the absence of disease progression or unacceptable toxicity.

HER2Bi-Armed Activated T Cells

Laboratory Biomarker Analysis

Lawrence Lum

This phase I trial studies the side effects and best dose of activated T-cell therapy when given together with low-dose aldesleukin and sargramostim in treating patients with ovarian, fallopian tube, or primary peritoneal cancer that is stage III-IV, has not responded to previous treatment, or has come back. Activated T cells that have been coated with bi-specific antibodies, such as anti-cluster of differentiation (CD)3 and anti-human epidermal growth factor receptor 2 (HER2), may stimulate the immune system in different ways and stop tumor cells from growing. Aldesleukin may stimulate white blood cells to kill tumor cells. Colony-stimulating factors, such as sargramostim, may increase the production of blood cells. Giving activated T-cell therapy with low-dose aldesleukin and sargramostim may be a better treatment for ovarian, fallopian tube, or primary peritoneal cancer.

PRIMARY OBJECTIVES:

I. Perform a phase I clinical trial consisting of dose-escalation/de-escalation of intraperitoneal (IP) infusions of anti-CD3 x anti-HER2/neu (HER2Bi) armed anti-CD3 activated T cells (aATC) in women with high risk or recurrent ovarian cancer to determine the maximum tolerated dose (MTD) for IP injections in combination with a fixed intravenous (IV) dose of 10 x 10\^9 (± 20%) aATC once a week.

II. To clearly define the toxicity profile of IP and IV HER2Bi aATC at the MTD or technically feasible dose in patients with ovarian cancer.

SECONDARY OBJECTIVES:

I. Evaluate clinical responses, time to progression, and overall survival. II. Evaluate phenotype, cytokine profiles and interferon (IFN)-gamma enzyme-linked immunosorbent spots (ELISPOTS), cytotoxicity and antibodies directed at laboratory ovarian cancer cell lines.

III. Monitor cancer antigen (CA)125 or tumor markers, and antibody responses to mouse proteins (human anti-mouse antibodies \[HAMA\]).

IV. The migration of armed ATC out of the peritoneal and serum cytokine levels induced by IP or IV armed ATC infusion will be assessed by studying the appearance of armed ATC at various time points (0, 4, 8, 12, 24, 48, 72, and 96 hours after IP infusion) in the blood after IP infusions by performing flow cytometry to detect anti-CD3 (OKT3) x anti-Her2 (Herceptin®) bi-specific antibody (BiAb) on the surface of aATC.

OUTLINE: This is a dose-escalation study of IP infused HER2Bi-armed activated T cells.

Patients receive HER2Bi-aATC IV over 5-15 minutes and IP within 3-4 days of IV dose weekly for 4 weeks. Patients also receive low-dose aldesleukin subcutaneously (SC) daily and sargramostim SC twice weekly beginning 3 days before the first HER2Bi-aATC infusions infusion and ending 7 days after the last HER2Bi-aATC infusion. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 1 and 3 months, and then every 6 months.

Activated T-cell Therapy, Low-Dose Aldesleukin, and Sargramostim in Treating Patients With Ovarian, Fallopian Tube, or Primary Peritoneal Cancer That is Stage III-IV, Refractory, or Recurrent

Treatment of High Risk or Recurrent Ovarian Cancer With Anti-CD3 x Anti-HER2 Bispecific Antibody Armed Activated T Cells (BATs), Low Dose IL-2, and GM-CSF (Phase I).

Patients who received any armed ATC but not evaluable for DLT will be analyzed separately for the toxicity profile. The toxicity will be summarized with point and exact confidence intervals.

Increases or decreases in the amount of cytokine produced from the pre immunotherapy baseline at any time point after immunotherapy will be considered as continuous outcomes. Paired t-test or Wilcoxon signed rank test will be used to compare the difference between baseline and after any time point of aATC treatment in proliferation, ELISPOTS, and the amount of cytokine produced. The data collected at all study time points after immunotherapy will be analyzed using mixed-effect model for longitudinal data adjusted for baseline measures.

Sera from patients will be obtained before and after immunotherapy at the designated time points to determine if there is development of HAMA responses directed at OKT3 (mouse IgG2a antibody). Paired t-test or Wilcoxon signed rank test will be used to compare the difference between baseline and after any time point of aATC treatment in proliferation, ELISPOTS, and the amount of cytokine produced. The data collected at all study time points after immunotherapy will be analyzed using mixed-effect model for longitudinal data adjusted for baseline measures.

PBMC from the patients will be obtained before and after immunotherapy to determine if there changes induced by immunotherapy. Paired t-test or Wilcoxon signed rank test will be used to compare the difference between baseline and after any time point of aATC treatment in proliferation, ELISPOTS, and the amount of cytokine produced. The data collected at all study time points after immunotherapy will be analyzed using mixed-effect model for longitudinal data adjusted for baseline measures.

Point and exact confidence interval estimates will be calculated for response rate.

Paired t-test or Wilcoxon signed rank test will be used to compare the difference between baseline and after any time point of aATC treatment in proliferation, ELISPOTS, and the amount of cytokine produced. The data collected at all study time points after immunotherapy will be analyzed using mixed-effect model for longitudinal data adjusted for baseline measures.

Sera from patients will be obtained before and after immunotherapy to determine if there are changes induced by immunotherapy. Paired t-test or Wilcoxon signed rank test will be used to compare the difference between baseline and after any time point of aATC treatment in proliferation, ELISPOTS, and the amount of cytokine produced. The data collected at all study time points after immunotherapy will be analyzed using mixed-effect model for longitudinal data adjusted for baseline measures.

Will be estimated with the standard Kaplan-Meier method, from which summary statistics of interest (median, 6 month, 1-year rate, etc.) will be derived. Both point and 95% confidence interval estimates will be calculated.

National Cancer Institute (NCI)

Barbara Ann Karmanos Cancer Institute

Principal Investigator

Skin and Connective Tissue Diseases

Adenocarcinoma

Carcinoma, Transitional Cell

Cystadenocarcinoma, Serous

Adenocarcinoma, Clear Cell

Adenocarcinoma, Mucinous

Cystadenocarcinoma

Brenner Tumor

Carcinoma, Endometrioid

Neoplasms, Cystic, Mucinous, and Serous

Endometrial Neoplasms

Uterine Neoplasms

Neoplasms, Fibrous Tissue

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Transitional Cell Carcinoma

Adenocarcinoma of the Appendix

Brenner Tumor of Ovary

Patients undergo collection of serum samples for analysis of YKL-40 via ELISA and CA125 via chemiluminometric sandwich immunoassay at the following time-points: at baseline; prior to beginning each course of chemotherapy (courses 1-6); at completion of chemotherapy; every 3 months during years 1-2 post-chemotherapy; every 6 months during years 3-5 post-chemotherapy; every year during years 6-10 post-chemotherapy; and at time of disease recurrence or progression.

Cytology Specimen Collection Procedure

Katherine Bell-McGuinn

This research trial studies chitinase 3-like 1 (cartilage glycoprotein-39) (YKL-40) in serum samples from patients with newly diagnosed stage III-IV ovarian epithelial, primary peritoneal cavity, or fallopian tube cancer receiving chemotherapy. Studying samples of serum in the laboratory from patients receiving chemotherapy may help doctors learn more about the effects of chemotherapy on cells. It may also help doctors understand how well patients respond to treatment.

PRIMARY OBJECTIVES:

I. To assess the ability of the YKL-40 serum marker to detect response or lack of response to primary chemotherapy in International Federation of Gynecology and Obstetrics (FIGO) stage III or IV invasive epithelial ovarian, primary peritoneal, or fallopian tube cancer.

II. To compare the predictive accuracy of YKL-40 with cancer antigen 125 (CA125).

SECONDARY OBJECTIVES:

I. To test the ability of the YKL-40 serum marker to detect recurrence of ovarian, primary peritoneal, or fallopian tube cancer in patients who are in first remission following primary chemotherapy.

II. To test the ability of the YKL-40 serum marker to predict poor risk patients with FIGO stage III or IV invasive epithelial ovarian, primary peritoneal, or fallopian tube cancer.

TERTIARY OBJECTIVES:

I. To explore alternative cut-off values for YKL-40 elevation in this large patient population.

II. To describe the variability of YKL-40 and CA125 measurements in patients receiving primary chemotherapy and in primary remission in a large patient population.

III. To describe the accuracy of YKL-40 coupled with CA125 measurements in predicting chemotherapy response, progression-free survival and overall survival.

OUTLINE:

Patients undergo collection of serum samples for analysis of YKL-40 via enzyme-linked immunosorbent assay (ELISA) and CA125 via chemiluminometric sandwich immunoassay at the following time-points: at baseline; prior to beginning each course of chemotherapy (courses 1-6); at completion of chemotherapy; every 3 months during years 1-2 post-chemotherapy; every 6 months during years 3-5 post-chemotherapy; every year during years 6-10 post-chemotherapy; and at time of disease recurrence or progression.

YKL-40 in Serum Samples From Patients With Newly Diagnosed Stage III-IV Ovarian Epithelial, Primary Peritoneal Cavity, or Fallopian Tube Cancer Receiving Chemotherapy

A Prospective, Longitudinal Study of YKL-40 in Patients With FIGO Stage III or IV Invasive Epithelial Ovarian, Primary Peritoneal or Fallopian Tube Cancer Undergoing Primary Chemotherapy

As an exploratory analysis, the accuracy of YKL-40 coupled with CA125 measurements in predicting chemotherapy response will be described.

Optimal cut-off values for YKL-40 that subsequently can be used in clinical practice will be determined. Any statistical significance calculated for an optimized cut-off will adjust for the selection process, and any comparison with CA-125 will treat both markers in the same way.

As an exploratory analysis, the accuracy of YKL-40 coupled with CA125 measurements in predicting overall survival will be described.

As an exploratory analysis, the accuracy of YKL-40 coupled with CA125 measurements in predicting progression-free survival will be described.

Linear statistical methods, such as a random effects model, will be used to assess the variability and correlation of CA125 over time in this population.

Linear statistical methods, such as a random effects model, will be used to assess the variability and correlation of YKL-40 over time in this population.

The accuracy of each marker alone will be compared using area under the ROC curve, and assess which adds more predictive information when both are included in logistic regression.

In order to make a valid comparison between CA125 and YKL-40, in this study computed tomography (CT) criteria will be treated as the "gold standard" and whether changes in YKL-40 levels correlate with CT evidence as well as or better than changes in CA125 levels will be evaluated.

Parallel statistical analyses of time to disease progression will also be conducted for patients who do not respond.

Parallel analyses of the markers as predictors of time-to-relapse will be performed using survival-type regression methods such as the Cox proportional hazards model or a parametric maximum likelihood model. The total number of patients available for analysis of time to relapse is the number of patients who respond to treatment.

YKL-40 will be compared to CA125 in terms of its ability to detect response to chemotherapy (during chemotherapy) and recurrence of disease (in remission). Serum YKL-40 behavior will also be assessed as a reflection of tumor histology, tumor grade, and tumor stage-all in comparison to CA125. The accuracy of each marker alone will be compared using area under the receiver operating characteristic (ROC) curve, and assess which adds more predictive information when both are included in logistic regression.

Gynecologic Oncology Group

Respiratory System Agents

Topotecan

Acetylcysteine

N-monoacetylcystine

Topoisomerase I Inhibitors

Enzyme Inhibitors

Expectorants

Antioxidants

Protective Agents

Antidotes

Cysteine

Patients receive topotecan hydrochloride IV over 30 minutes on days 1, 8, and 15 (+/- 1 day window for each treatment day). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients receive topotecan hydrochloride as in Arm I. Patients also receive acetylcysteine IV over 60 minutes on days 1, 8, 15, and 22 (+/- 1 day window for each treatment day) and acetylcysteine PO BID on days 2-7, 9-14, 16-21, and 23-28, unless administration window was utilized. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Topotecan Hydrochloride

Russell Schilder, MD

This randomized phase II trial studies the effects of acetylcysteine and topotecan hydrochloride on the tumor microenvironment, or cells that make up a tumor, compared to topotecan hydrochloride alone in patients with ovarian, fallopian tube, or primary peritoneal cancer that has not responded to treatment (persistent) or has returned after a period of improvement (recurrent) and is high grade (likely to grow and spread quickly). Research has shown that cancer cells may be able to convert nearby normal cells into cancer cells. Acetylcysteine may stop this from happening. Topotecan hydrochloride is a chemotherapy drug used to treat ovarian cancer, and may help acetylcysteine work better. This trial studies the effect of acetylcysteine and topotecan hydrochloride on the tumor microenvironment to see if they can help make it more difficult for tumor cells to grow.

PRIMARY OBJECTIVES:

I. To estimate the proportion of subjects with persistent or recurrent high grade endometrioid or serous ovarian carcinoma who demonstrate a downregulation of monocarboxylate transporter 4 (MCT4) in the ovarian stroma in response to exposure to topotecan (topotecan hydrochloride) and N-acetylcysteine (NAC) (acetylcysteine) as compared to topotecan alone.

SECONDARY OBJECTIVES:

I. To determine the expression levels of caveolin 1 (Cav-1), solute carrier family 16 (monocarboxylate transporter), member 1 (MCT1), translocase of outer mitochondrial membrane 20 homolog (yeast) (TOMM20), fatty acid binding protein 4, adipocyte (FABP4), hypoxia inducible factor 1, alpha subunit (HIF-1 alpha) and NF kappaB activating protein (NFκB) in pathological samples of tumors after therapy with NAC relative to samples taken at time of initial diagnosis.

II. To assess the potential impact of NAC on progression free survival, overall survival, objective tumor response- complete or partial, and duration of response.

III. To estimate the proportion of subjects who survive progression free for at least 6 months and the proportion of patients who have objective tumor response, complete or partial in response to therapy IV. To assess safety and tolerability of NAC plus topotecan treatment in subjects with endometrioid or serous ovarian carcinoma by Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0 criteria.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive topotecan hydrochloride intravenously (IV) over 30 minutes on days 1, 8, and 15 (+/- 1 day window for each treatment day). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive topotecan hydrochloride as in Arm I. Patients also receive acetylcysteine IV over 60 minutes on days 1, 8, 15, and 22 (+/- 1 day window for each treatment day) and acetylcysteine orally (PO) twice daily (BID) on days 2-7, 9-14, 16-21, and 23-28, unless administration window was utilized. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 24 months.

Effect of Acetylcysteine With Topotecan Hydrochloride on the Tumor Microenvironment in Patients With Persistent or Recurrent High Grade Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

Evaluation of the Addition of N-Acetylcysteine to Topotecan in the Tumor Microenvironment of Persistent or Recurrent High Grade Endometrioid or Serous Ovarian Carcinoma

The two-sided Fisher's exact test with alpha 0.05 will be used to compare the proportions of subjects who demonstrate a downregulation of MCT4 between subjects treated with topotecan hydrochloride and NAC and topotecan hydrochloride alone.

Evaluated in a generalized linear mixed effects model adjusting for the random subject effects. The expression levels will be log or otherwise transformed, if necessary, to satisfy the normal distribution assumption of the model. The fitted model will be used to evaluate the post-treatment change in the expression levels.

Compared pre-therapy and post- 1 cycle of therapy with a Fisher's exact test.

Compared between the two arms using the log-rank test.

Evaluated using the exact binomial confidence intervals and compared between the two arms using the Fisher's exact test.

Compared between the two arms using the two-sample Wilcoxon test.

Tabulated and reported with the corresponding exact binomial confidence intervals.

National Institutes of Health (NIH)

Sidney Kimmel Cancer Center at Thomas Jefferson University

Patients receive topotecan hydrochloride IV over 30 minutes on days 1, 8, and 15 (+/- 1 day window for each treatment day). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Topotecan Hydrochloride: Given IV

Arm I (Topotecan Hydrochloride)

Patients receive topotecan hydrochloride as in Arm I. Patients also receive acetylcysteine IV over 60 minutes on days 1, 8, 15, and 22 (+/- 1 day window for each treatment day) and acetylcysteine PO BID on days 2-7, 9-14, 16-21, and 23-28, unless administration window was utilized. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Topotecan Hydrochloride: Given IV

Acetylcysteine: Given IV and PO

Arm II (Topotecan Hydrochloride, Acetylcysteine)

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Russell Schilder

The trial was halted prematurely due to slow accrual. Data were not collected and the Outcome will never be analyzed.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Activated T-cell Therapy, Low-Dose Aldesleukin, and Sargramostim in Treating Patients With Ovarian, Fallopian Tube, or Primary Peritoneal Cancer That is Stage III-IV, Refractory, or Recurrent	NCT02470559	Malignant Ovari... Malignant Ovari... Recurrent Fallo... Recurrent Ovari... Recurrent Prima... Stage IIIA Fall... Stage IIIA Ovar... Stage IIIA Prim... 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...	Aldesleukin HER2Bi-Armed Ac... Laboratory Biom... Sargramostim	18 Years -	Barbara Ann Karmanos Cancer Institute
YKL-40 in Serum Samples From Patients With Newly Diagnosed Stage III-IV Ovarian Epithelial, Primary Peritoneal Cavity, or Fallopian Tube Cancer Receiving Chemotherapy	NCT00899093	Fallopian Tube ... Fallopian Tube ... Fallopian Tube ... Fallopian Tube ... Fallopian Tube ... Fallopian Tube ... Malignant Ovari... Malignant Ovari... Malignant Ovari... Malignant Ovari... Malignant Ovari... Malignant Ovari... Malignant Ovari... Malignant Ovari... Ovarian Adenoca... Primary Periton... Stage IIIA Fall... Stage IIIA Ovar... Stage IIIA Prim... 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... Undifferentiate... Undifferentiate...	Cytology Specim... Laboratory Biom...	18 Years -	GOG Foundation
Effect of Acetylcysteine With Topotecan Hydrochloride on the Tumor Microenvironment in Patients With Persistent or Recurrent High Grade Ovarian, Primary Peritoneal, or Fallopian Tube Cancer	NCT02569957	Malignant Ovari... Malignant Ovari... Recurrent Fallo... Recurrent Ovari... Recurrent Prima...	Topotecan Hydro... Topotecan Hydro... Acetylcysteine	18 Years -	Thomas Jefferson University
Effect of Acetylcysteine With Topotecan Hydrochloride on the Tumor Microenvironment in Patients With Persistent or Recurrent High Grade Ovarian, Primary Peritoneal, or Fallopian Tube Cancer	NCT02569957	Malignant Ovari... Malignant Ovari... Recurrent Fallo... Recurrent Ovari... Recurrent Prima...	Topotecan Hydro... Topotecan Hydro... Acetylcysteine	18 Years -	Thomas Jefferson University

Spots Global Cancer Trial Database for malignant ovarian serous tumor