Paclitaxel and Intraperitoneal Carboplatin Followed by Radiation Therapy in Treating Patients With Stage IIIC-IV Uterine Cancer

Endometrial Serous Adenocarcinoma Clinical Trial

Official title:

A Pilot Phase II Trial of Intravenous Paclitaxel and Intraperitoneal Carboplatin Followed by Radiation in Patients With Advanced Stage Uterine Serous Carcinoma

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02112552
• Other study ID #: 13-02-058
• Secondary ID: NCI-2013-0122613
• Status: Terminated
• Phase: Phase 2
• Start date: April 10, 2014
• Est. completion date: December 1, 2017

Study information

• Verified date: July 2023
• Source: Albert Einstein College of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This pilot, phase II trial studies the side effects and how well paclitaxel given into the vein and carboplatin given directly into the abdominal cavity (intraperitoneally) followed by radiation therapy work in treating patients with stage IIIC-IV serous uterine cancer. 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, stopping them from dividing, or stopping them from spreading. Giving the drugs in different ways may kill more tumor cells. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving chemotherapy followed by radiation therapy may be an effective treatment for uterine cancer.

Description:

PRIMARY OBJECTIVES:

I. To evaluate the toxicity (as defined by National Cancer Institute [NCI] Common Toxicity Criteria version [v.] 4.0) of weekly intravenous (IV) paclitaxel with intraperitoneal (IP) carboplatin chemotherapy given every third week, followed by radiation therapy (RT) in patients with advanced stage uterine serous cancer (USC).

II. To determine the feasibility of this regimen in women with advanced stage USC.

SECONDARY OBJECTIVES:

I. To assess the frequency and the reasons for early discontinuation of the study treatments.

II. To describe patient-reported quality of life parameters at specified time points during the study using validated questionnaires: European Organization for Research and the Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 and QLQ-ovarian cancer module (OV)28.

TERTIARY OBJECTIVES:

I. To define patterns of recurrence (e.g. local versus distant) and progression-free survival in patients with advanced and recurrent USC treated with dose dense IV paclitaxel and IP carboplatin therapy.

II. To correlate surrogate endpoint biomarkers that is performed in standard histology processing (estrogen receptor and progesterone receptor status as well as human epidermal growth factor 2 [Her2/neu] status) with progression-free survival and prognosis.

III. To assess the potential late effects of combined intraperitoneal chemotherapy and radiotherapy on the gastrointestinal, genitoureteral, bone marrow and other body systems beginning at 6 months post treatment completion during routine office visits.

OUTLINE:

CHEMOTHERAPY: Patients receive paclitaxel intravenously (IV) over 1 hour on days 1, 8, and 15 and carboplatin intraperitoneally (IP) on day 1. Treatment repeats every 21 days for up to 6 courses (weeks 1-18) in the absence of disease progression or unacceptable toxicity.

RADIATION: At provider discretion, patients may undergo 3-dimensional (3D) conformal or intensity-modulated radiation therapy (IMRT) 5 days a week for 5 weeks (weeks 19-23).

After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then yearly thereafter for up to 10 years.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: December 1, 2017
• Est. primary completion date: August 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histological/cytologically documented primary International Federation of Gynecology and Obstetrics (FIGO) stage 3C1, 3C2, stage 4A, and 4B uterine serous carcinoma; in addition, certain stage 3A and B disease are also allowed

• Residual disease after primary surgery:

• Eligible:

• Stage 3A and B (pelvic, but confined to adnexa or vagina), residual disease present

• Stage 3CI (pelvic node positive)

• Stage 3CII (para-aortic node positive)

• Stage 4A (bladder or pelvic bowel)

• Stage 4B (distant metastases [mets] including abdominal mets), completely resected

• Not eligible

• Stage 3A and B (pelvic, but confined to adnexa or vagina), completely resected

• Stage 4B (distant mets including abdominal mets), residual disease present

• All patients must have a procedure for determining diagnosis of high-risk uterine cancer (HRUC); minimum surgical intervention required is tissue biopsy (may be from endometrium), if significant clinical evidence exists to support a stage 3 or 4 diagnosis; as per the discretion of the surgeon, complete surgical staging should include: total abdominal hysterectomy, bilateral salpingo-oophorectomy, peritoneal washings, omental biopsy and lymph node samplings; this is typically the standard unless the disease is bulky or the clinician feels the patient would be best served by chemotherapy and radiation therapy after histologic diagnosis is confirmed

• Eastern Cooperative Oncology Group (ECOG) performance status of =< 2

• Written voluntary informed consent

Exclusion Criteria:

• Distant metastasis to the lung, bone or brain; typically, most stage 4 uterine papillary serous cancer (UPSC) is confined to the abdomen on presentation

• Serum glutamic oxaloacetic transaminase (SGOT) and/or serum glutamate pyruvate transaminase (SGPT) > 2.5 times the institutional upper limit of normal (ULN)

• Total serum bilirubin > 1.5 mg/dl

• Serum creatinine > 2.0 mg/dl

• Platelets < 100,000/mm^3

• Absolute neutrophil count (ANC) < 1500/mm^3

• Hemoglobin < 8.0 g/dl (the patient may be transfused prior to study entry)

• History of abdominal/pelvic radiation therapy

• Severe or uncontrolled, concurrent medical disease (e.g. uncontrolled diabetes, unstable angina, myocardial infarction within 6 months, congestive heart failure, etc.)

• Patients with dementia or altered mental status that would prohibit the giving and understanding of informed consent at the time of study entry

Related Conditions & MeSH terms

• Endometrial Serous Adenocarcinoma
• Stage IIIA Uterine Corpus Cancer
• Stage IIIB Uterine Corpus Cancer
• Stage IIIC1 Uterine Corpus Cancer
• Stage IIIC2 Uterine Corpus Cancer
• Stage IVA Uterine Corpus Cancer
• Stage IVB Uterine Corpus Cancer

Intervention

Drug:
• Paclitaxel
Given IV
• Carboplatin
Given IP

Radiation:
• 3-Dimensional Conformal Radiation Therapy
Undergo 3D conformal radiation therapy
• Intensity-Modulated Radiation Therapy
Undergo IMRT

Other:
• Quality-of-Life Assessment
Ancillary studies
• Laboratory Biomarker Analysis
Correlative studies

Locations

Country	Name	City	State
United States	Albert Einstein College of Medicine	Bronx	New York

Sponsors (2)

Lead Sponsor	Collaborator
Albert Einstein College of Medicine	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Degree of Tolerability, Estimated by the Proportion of Participants Who Complete 6 Treatment Cycles of IP Carboplatin	At the end of the study, the proportion of patients who tolerated the therapy will be estimated, along with corresponding 95% confidence intervals. Reasons for discontinuation of therapy will be categorized and summarized by computing frequencies.	Up to 18 weeks
Secondary	Progression-free Survival	The proportion of responders at one year will be estimated with the Kaplan-Meier method. Surrogate endpoint biomarkers including estrogen, progesterone, and Her2/neu receptor status will be correlated with progression-free survival using the Cox Proportional Hazards model, provided the availability of a sufficient number of events.	The duration of time from start of treatment to time of progression, or death, whichever happens first, assessed at 1 year