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 | Terminated Phase 2 Results DMC

• 2 other identifiers: 15P.404JT 7408
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Malignant Ovarian Endometrioid Tumor; Malignant Ovarian Serous Tumor; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma

Outcome Measures

Primary Outcomes (1)

• Proportion of Patients Who Demonstrate a Downregulation of MCT4

  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.

  Baseline to up to day 20 after first course of topotecan hydrochloride

Secondary Outcomes (12)

• Change in Expression Levels of Cav-1 in Tissue Samples

  Baseline to up to day 20 after first course of topotecan hydrochloride

• Change in Expression Levels of MCT1 in Tissue Samples

  Baseline to up to day 20 after first course of topotecan hydrochloride

• Change in Expression Levels of TOMM20 in Tissue Samples

  Baseline to up to day 20 after first course of topotecan hydrochloride

• Change in Expression Levels of FABP4 in Tissue Samples

  Baseline to up to day 20 after first course of topotecan hydrochloride

• Change in Expression Levels of HIF-1 Alpha in Tissue Samples

  Baseline to up to day 20 after first course of topotecan hydrochloride

Study Arms (2)

Arm I (topotecan hydrochloride)

ACTIVE COMPARATOR

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.

Drug: Topotecan Hydrochloride

Arm II (topotecan hydrochloride, acetylcysteine)

EXPERIMENTAL

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.

Drug: Topotecan Hydrochloride; Drug: Acetylcysteine

Interventions

Topotecan Hydrochloride DRUG

Given IV

Also known as: Hycamtin

Arm I (topotecan hydrochloride)

Acetylcysteine DRUG

Given IV and PO

Also known as: N-acetylcysteine, N-acetyl-L-cysteine (NAC)

Arm II (topotecan hydrochloride, acetylcysteine)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must have persistent or recurrent high grade endometrioid or serous ovarian, primary peritoneal or fallopian tube carcinoma. Histologic documentation of the original primary tumor is required via the pathology report.
• All patients must have measurable disease that is amenable to biopsy. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded). Each lesion must be ≥20 mm when measured by conventional techniques including palpation, plain film x-ray, CT, and MRI, or ≥ 10 mm when measured by high resolution CT.
• Patient must have at least one target lesion to be used to assess response on this protocol as defined by RECIST 1.1. Tumors within a previously irradiated field will be designated as non-target lesions unless progression is documented or a biopsy is obtained to confirm persistent disease at least 90 days following completion of radiation therapy.
• Patients must have a GOG performance status of 0, 1, or 2.
• Patients must be free of active infections requiring antibiotics, with the exception of uncomplicated urinary tract infections (UTIs).
• Any hormonal therapy directed at the tumor must be discontinued at least one week prior to initiation of therapy. Continuation of hormone replacement therapies is permitted.
• Any other prior therapy directed at the tumor, including immunologic agents, must be discontinued at least 3 weeks prior to initiation of therapy.
• Patients must have had at least one prior platinum/taxane combination chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatin compound. This initial treatment may include intraperitoneal therapy, high dose therapy, consolidation, noncytotoxic agents, or extended therapy.
• Patients must be platinum resistant- defined as progressive disease while receiving platinum therapy or within 6 months of completing first line platinum therapy or patients who have progressive disease after two lines of platinum based treatment.
• Cytotoxic regimens are any that include agents that target the genetic and/or mitotic apparatus of the dividing cells, resulting in dose limiting toxicity to the bone marrow or gastrointestinal mucosa
• Patients are allowed to receive, but not required to receive biologic (noncytotoxic) therapy as part of their treatment regimen, e.g. bevacizumab.
• Patients Must Have Adequate:
• Bone Marrow Function: Absolute Neutrophil Count greater than or equal to 1000/mcl. Platelets greater than or equal to 100,000/mcl. Hemoglobin greater than 10 g/dl. (Patients may be transfused to achieve this hemoglobin.)
• Renal Function: creatinine less than or equal to 1.5 x upper limit of normal, CTCAE v 4.0 grade 1.
• Hepatic Function: bilirubin less than or equal to 1.5 x upper limit of normal, CTCAE v 4.0 grade 1. Asparate transaminase (AST) and alkaline phosphatase less than or equal to 2.5 x upper limit of normal, CTCAE v 4.0 grade 1.

You may not qualify if:

• Patients who have had previous treatment with topotecan.
• Patients who have had more than 4 prior chemotherapy regimens.
• Patients who have received radiation to more than 25% of marrow-bearing areas.
• Patients with a history of other invasive malignancies are excluded if there is any evidence of other malignancy being present within the last 3 years.
• Patients who have received prior chemotherapy for any abdominal or pelvic tumor other than for treatment of ovarian carcinoma within the last 3 years are excluded. Patients may have received prior chemotherapy for localized breast cancer, provided that it was completed more than three years prior to registration and the patient remains free of recurrent of metastatic disease.
• Pregnant or nursing women or women of childbearing potential unless using effective contraception as determined by the investigator. -

Sponsors & Collaborators

• Sidney Kimmel Cancer Center at Thomas Jefferson University: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Links

• Jefferson University Hospitals

MeSH Terms

Conditions

Fallopian Tube Neoplasms; Ovarian Neoplasms

Interventions

Topotecan; Acetylcysteine

Condition Hierarchy (Ancestors)

Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Fallopian Tube Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Russell Schilder
• Organization: Sidney Kimmel Cancer Center at Thomas Jefferson University

russell.schilder@jefferson.edu

215-503-3057

Study Officials

• Russell Schilder, MD

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2015
• First Posted: October 7, 2015
• Study Start: October 2, 2015
• Primary Completion: June 10, 2016
• Study Completion: October 12, 2017
• Last Updated: May 4, 2025
• Results First Posted: January 3, 2018

Record last verified: 2025-05

Locations

US (1)