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Malignant Ovarian Endometrioid TumorPhase 2NCT02569957

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

A Phase 2 study testing Topotecan Hydrochloride and Acetylcysteine in people with Malignant Ovarian Endometrioid Tumor and Malignant Ovarian Serous Tumor, run by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Topotecan Hydrochloride and Acetylcysteine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1 participants
Where
1 siteUnited States
Study dates
2 Oct 2015to 12 Oct 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.
  • Coagulation: PT, PTT less than or equal to 1 to 1.5 x upper limit of normal CTCAE v 4.0 grade 1 except for patients on therapeutic anticoagulation.
  • Neurologic Function: neuropathy (sensory and motor) less than or equal to CTCAE v 4.0 grade 1.
  • Patients must have signed an approved informed consent and authorization permitting release of personal health information.
  • Patients must meet pre-entry requirements as specified.
  • In the unlikely event that patients are still of childbearing potential, these patients must have a negative serum pregnancy test within 72 hours prior to initiating protocol therapy and be practicing an effective form of contraception during protocol therapy and for at least 4 weeks following completion of protocol therapy.
  • Patients must be 18 years of age or older.
  • Patients must not be receiving any other investigational agent.
  • Patients must be able to swallow whole pills. -

Who cannot join

  • 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. -

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

Being tested
Topotecan Hydrochloride, Acetylcysteine
Medical subject headings
Fallopian Tube Neoplasms, Ovarian Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Topotecan HydrochlorideDrug

    Also called Hycamtin

    Given IV

  • Topotecan HydrochlorideDrug

    Also called Hycamtin

    Given IV

  • AcetylcysteineDrug

    Also called N-acetylcysteine, N-acetyl-L-cysteine (NAC)

    Given IV and PO

Study groups in NCT02569957
Study groupRoleWhat they receive
Arm I (topotecan hydrochloride)Active comparatorPatients 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.
Receives: Drug: Topotecan Hydrochloride
Arm II (topotecan hydrochloride, acetylcysteine)ExperimentalPatients 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.
Receives: Drug: Topotecan Hydrochloride; Drug: Acetylcysteine

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (12)

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

    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.

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

  2. Change in Expression Levels of MCT1 in Tissue Samples

    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.

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

  3. Change in Expression Levels of TOMM20 in Tissue Samples

    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.

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

  4. Change in Expression Levels of FABP4 in Tissue Samples

    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.

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

  5. Change in Expression Levels of HIF-1 Alpha in Tissue Samples

    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.

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

  6. Change in Expression Levels of NFκB in Tissue Samples

    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.

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

  7. Change in Number of Circulating Tumor Cells

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

    Measured: Baseline to day 29

  8. Progression-free Survival

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

    Measured: Up to 24 months

  9. Overall Survival

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

    Measured: Up to 24 months

  10. Objective Tumor Response Rates

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

    Measured: Up to 24 months

  11. Duration of Response

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

    Measured: Up to 24 months

  12. Proportion of Patients Experiencing Adverse Events, Evaluated Using the National Cancer Institute CTCAE Version 4.0

    Tabulated and reported with the corresponding exact binomial confidence intervals.

    Measured: Up to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Oct 2015 (estimated)
  2. Study start2 Oct 2015
  3. Primary completion10 Jun 2016
  4. Study completion12 Oct 2017

Why it stopped: The trial was halted prematurely due to slow accrual.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02569957
Sponsor's protocol ID
15P.404
Other IDs
JT 7408
Status last verified
May 2025
First submitted
5 Oct 2015
Last updated
4 May 2025
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Topotecan Hydrochloride and Acetylcysteine in people with Malignant Ovarian Endometrioid Tumor and Malignant Ovarian Serous Tumor, run by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 4 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Jan 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of Patients Who Demonstrate a Downregulation of MCT4 (time frame: Baseline to up to day 20 after first course of topotecan hydrochloride). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02569957.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2025.

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