Neoplasms

All Conditions

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Recurrence

Uterine Neoplasms

Cystadenocarcinoma, Serous

Cystadenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Adenocarcinoma

Neoplasms, Cystic, Mucinous, and Serous

Adenocarcinoma of the Appendix

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Paclitaxel

Albumin-Bound Paclitaxel

Imatinib Mesylate

Tubulin Modulators

Antimitotic Agents

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Phase I MTD using oral dose Imatinib Mesylate escalation 400, 500, 600 mg daily; Paclitaxel 175 mg/m\^2 every 21 days

Intended randomization of Paclitaxel alone or Paclitaxel + Imatinib Mesylate; the study was terminated early due to poor enrollment and all patients are no longer being treated or followed. Single treatment arm MTD using oral dose Imatinib Mesylate escalation = 500 mg daily; Paclitaxel 175 mg/m\^2 every 21 days

Phase II, (Arm 1) = Paclitaxel 175 mg/m\^2 every 21 days Phase II, (Arm 2) Paclitaxel 175 mg/m\^2 every 21 days+ Imatinib Mesylate MTD using oral dose Imatinib Mesylate escalation = 500 mg daily

Phase I = Maximum tolerated dose (MTD) derived from dose escalation of 400, 500, 600 mg by mouth daily

175 mg/m\^2 by vein over 3 Hours every 21 Days

Objectives:

* To determine the maximum tolerated dose (MTD) of imatinib mesylate in combination with fixed dose paclitaxel in patients with stage IIIC, IV or recurrent uterine papillary serous carcinoma.
* To determine the nature and degree of toxicity of imatinib mesylate and paclitaxel in this cohort of patients.
* To determine the efficacy of imatinib mesylate and paclitaxel in patients with stage IIIC, IV or recurrent uterine papillary serous carcinoma whose tumor expresses either c-Kit, PDGFR or abl.

Before possible study participants can receive treatment with imatinib mesylate and paclitaxel, their tumor tissue that was previously collected (at the surgery to diagnose your tumor) will be tested for the following three biomarkers: c-Kit, PDGFR-B, and Abl. Those participants who have at least one positive biomarker will be eligible for treatment on this study.

Paclitaxel is a chemotherapy drug used in the treatment of ovarian cancer. Imatinib mesylate is a medication that blocks several proteins that are important in the development of cancer.

Before treatment starts, you will have a complete physical exam, routine blood tests (about 2-3 teaspoons), an electrocardiogram (ECG--a test to measure the electrical activity of the heart). You will have an echocardiogram (an ultrasound test used to visualize the structures of the heart), a chest x-ray, and a CT scan or MRI of the abdomen and pelvis. Women who are able to have children must have a negative blood pregnancy test.

Routine blood tests (about 2 teaspoons) will be done weekly during treatment, and before each course of therapy, which is every 3 weeks. A complete checkup including evaluation of side effects, will also be done before each course of therapy and at the end of therapy (3 weeks after treatment ends).

There are two phases to this study, Phase I and Phase II. If you are assigned to Phase 1, you will receive treatment with imatinib mesylate and paclitaxel. Phase 1 will study 3 different doses of imatinib mesylate in combination with a fixed dose of paclitaxel. The Phase I part of the study will help researchers learn the most effective dose of imatinib mesylate to be used in combination with paclitaxel. All participants in Phase 1 will receive one of three doses of imatinib mesylate to be given with a standard dose of paclitaxel. You will be assigned to a specific dose level based on the number of participants treated at the time of your enrollment.

The Phase II portion of the study will begin only after the most effective dose of imatinib mesylate has been determined.

If you are assigned to Phase II, you will be randomly assigned (as in the toss of a coin) to one of two treatment groups. Participants in one group will receive treatment with paclitaxel only (every 21 days). Participants in the second group will receive treatment with paclitaxel (every 21 days) along with imatinib mesylate (every day). The dose level of imatinib mesylate that you receive will be the same as the dose used during Phase I. The computer-generated assignment will favor the treatment group which is more effective. For example, if the combination of paclitaxel and imatinib mesylate is more effective than paclitaxel alone, then more patients will be selected to receive the combination therapy.

You will receive paclitaxel by vein over 3 hours every 21 days. Those participants who are assigned treatment with both paclitaxel and imatinib mesylate will begin taking imatinib mesylate the day after the first dose of paclitaxel. A single dose of imatinib mesylate will be taken by mouth every day.

Evaluation of tumor response (for participants who already have the disease) will be determined by CT scan or MRI and chest x-ray (patients with chest disease). These scans will be taken after Courses 2 and 4 , then after every 3 courses until the therapy is finished, and once more at the end of therapy. Patients who show no signs of the disease will be given a total of up to 6 courses. Patients who have the disease may continue treatment until the disease gets worse. You will be taken off study if the disease gets worse or intolerable side effects occur. If you are removed from the study, you will be asked to have a follow-up CT scan or MRI and chest x-ray to evaluate the tumor.

THIS IS AN INVESTIGATIONAL STUDY. Paclitaxel is commercially available and approved for use in the treatment of ovarian cancer. Gleevec® is also commercially available and approved for use in the treatment of certain types of adult leukemias and stomach cancers. The combination of paclitaxel and imatinib mesylate is still investigational and has been approved for use in research only.

At least 51 and as many as 65 participants will take part in this study. All participants will be enrolled and treated at M. D. Anderson.

Gleevec/Taxol for Patients With Uterine Papillary Serous Carcinoma

A Phase I/II Study of Gleevec/Taxol in Patients With Newly Diagnosed Stage IIIC or IV or Recurrent (Any Stage) Uterine Papillary Serous Carcinoma (UPSC)

Maximum Tolerated Dose (MTD) of Oral Imatinib Mesylate in Combination with Fixed Dose Paclitaxel where MTD of Imatinib Mesylate (mg/m\^2 daily) to be determined with conventional 3+3 design, MTD is highest dose level in which 6 participants treated with at most 2 experiencing dose limiting toxicity (DLT). Study utilizes Common Terminology for Adverse Events Criteria (CTCAE) version 3.0 for adverse event reporting.

Following cohorts of 3 at lower dose levels until 1 of 3 patients experiences DLT; if 1 of 3 patients experiences DLT at dose level, enter 3 additional patients at dose level, if only 1 of 6 patients experiences DLT at dose level, proceed to next higher dose level with cohort of 3; If 2 of 3 or 3 of 6 patients experience DLT, MTD has exceeded. Once DLT exceeded, treat another 3 patients at previous dose if there were only 3 patients treated at that dose level. MTD is highest dose level in which treated 6 patients with at most 2 experiencing the DLT.

Complete Response (CR): Disappearance lesions, no evidence new lesions documented by 2 disease assessments\> 4 weeks apart. Partial Response (PR):\>30% decrease in sum longest dimensions (LD) all target measurable lesions reference baseline sum of LD; No progression non-target lesions \& no new lesions; Documentation by 2 disease assessments \>4 weeks apart; Progressive Disease (PD) (ANY of following): \>20% increase in sum LD of target lesions reference smallest sum LD or appearance of new lesions within 8 weeks of study entry; Unequivocal progression on existing non-target lesions, other than pleural effusions without cytological proof of neoplastic origin, within 8 weeks of study entry also considered increasing disease. Death due to disease without prior objective documentation of progression; Global deterioration in health attributable to disease requiring change in therapy without objective evidence of progression. Stable disease: Any condition not meeting above criteria.

Efficacy of Gleevec and Taxol in Participants defined by tumor progression for participants with measurable disease or recurrent non-measurable disease. Time to tumor progression defined as the time from date of initial treatment to first objective documentation of disease progression. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded). After two cycles (6 weeks), participants will undergo clinical and radiographic (participants with measurable disease) tumor restaging or confirmation recurrent non-measurable disease. Evaluation of tumor response (for participants who already have the disease) determined by CT scan or MRI and chest x-ray (participants with chest disease).

M.D. Anderson Cancer Center

Cohort One = Paclitaxel (Taxol) 175 mg/m\^2 intravenous (IV) every 21 days + Imatinib Mesylate (Gleevec). Phase I Maximum Tolerated Dose (MTD) to be determined from escalating doses in subsequent cohorts: 400 (this arm, Cohort One), 500 (Cohort Two) or 600 mg (Cohort Three) orally daily.

Phase I: Imatinib Mesylate 400mg

Paclitaxel 175 mg/m\^2 IV every 21 days + Imatinib Mesylate 500 mg orally daily

Phase II: Imatinib Mesylate 500 mg

Paclitaxel 175 mg/m\^2 IV every 21 days + Imatinib Mesylate 600 mg orally daily

Phase 1: Imatinib Mesylate 600 mg

Paclitaxel 175 mg/m\^2 IV every 21 days + Imatinib Mesylate at MTD 500 mg orally

Phase II: Imatinib Mesylate MTD 500 mg

Phase I = Paclitaxel (Taxol) 175 mg/m\^2 intravenous (IV) every 21 days + Imatinib Mesylate (Gleevec) 400, 500 or 600 mg orally daily

Phase I: Paclitaxel + Imatinib Mesylate

Phase II = Paclitaxel 175 mg/m\^2 IV every 21 days + Imatinib Mesylate at MTD 500 mg orally daily

Phase II: Paclitaxel + Imatinib Mesylate MTD 500 mg

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

David Gershenson, MD

Cohort One = Paclitaxel 175 mg/m\^2 IV every 21 days + Imatinib Mesylate 400 mg orally daily

Imatinib Mesylate 400 mg

Cohort Two = Paclitaxel 175 mg/m\^2 IV every 21 days + Imatinib Mesylate 500 mg orally daily

Imatinib Mesylate 500 mg

Cohort Three = Paclitaxel 175 mg/m\^2 IV every 21 days + Imatinib Mesylate 600 mg orally daily

Imatinib Mesylate 600 mg

One participant of 12 registered withdrew prior to receiving treatment.

Number of Participants Who Experienced Dose Limiting Toxicities (DLTs)

Paclitaxel (Taxol) 175 mg/m\^2 intravenous (IV) every 21 days + Imatinib Mesylate (Gleevec) 400, 500 or 600 mg orally daily or Phase II MTD 500 mg

Participants With Measurable Disease

Participants With Non-Measurable Disease

Number of Participants With Complete Response

Due to poor enrollment, the study was terminated early and no data collected for the Time to tumor progression outcome measure.

Time to Tumor Progression

Phase I: Imatinib Mesylate 400 mg

Phase I: Imatinib Mesylate 500 mg

Phase I: Imatinib Mesylate 600 mg

Phase II, Cohort 4 = Paclitaxel 175 mg/m\^2 IV every 21 days + Imatinib Mesylate at MTD 500 mg orally daily

Overall Study

Carboplatin

Drug:Carboplatin and Paclitaxel and Radiation: Pelvic Radiation Therapy

Paclitaxel 175 mg/m2/3 hour \& Carboplatin (AUC=6.5) Repeat q 21 days x 3 cycles followed by RT followed by Paclitaxel 175 mg/m2/3 hour \& Carboplatin (AUC=5.0)Repeat q 21 days x 3 cycles

Carboplatin and Paclitaxel and Pelvic Radiation Therapy

Carboplatin and Paclitaxel and Radiation Therapy

Mark H Einstein, M.D., M.S.

Combination chemo/radiotherapy trials in advanced/recurrent endometrial cancer are ongoing. The optimal radiation modality, chemotherapeutic agents, and sequence of these regimens for the treatment of UPSC are yet to be established. A retrospective review of 16 patients treated at our institution with the sequential use of radiation "sandwiched" between paclitaxel/platinum chemotherapy found only one patient to have recurred at 16 months with a median follow-up of 15 months (range 6-33 months). The regimen was well tolerated. Eight of the sixteen patients (50%) developed grade 3 neutropenia following cycle 4 of chemotherapy, two of which required a 1 week treatment delay. There were no cases of grade 3 or 4 thrombocytopenia noted. There was no febrile neutropenia and no hospital admissions for toxicity. There were no observed grade 3 or 4 non-hematologic toxicities. With the median follow up of 15 months, we have not observed late toxicities.

Given these favorable preliminary findings, supported by recently published data documenting efficacy of the "sandwich" multimodality technique in other difficult uterine malignancies (malignant mixed mullerian tumors), we propose to study this combination of chemotherapy and radiation prospectively. Our aim is to better evaluate patterns of recurrence and possible benefits in progression-free and overall survival.

Uterine papillary serous carcinoma (UPSC) is an uncommon, but aggressive variant of endometrial carcinoma that has a high recurrence rate and poor response to therapy. It has a propensity to metastasize throughout the abdomen, similar to serous carcinoma of the ovary. In fact, many patients with disease apparently confined to the uterus have microscopic intra-abdominal spread at the time of diagnosis. Recurrences are common both in the pelvis as well as in the upper abdomen.

After staging and debulking of gross disease, adjuvant radiation therapy is recommended to treat patients with endometrial carcinoma at high risk for recurrent disease. High-risk features include histologic cell type, grade, depth of myometrial invasion, cervical extension, lymph-vascular invasion, adnexal involvement, intraperitoneal spread, positive peritoneal cytology, and positive lymph nodes. Pelvic radiation can limit local recurrences to less than 6.5%. However, approximately 25-30% of patients with high-risk features who receive radiation recur with distant metastases. Even patients treated with whole abdominal irradiation are at risk for extra-abdominal recurrences with progression-free intervals of 7 to 8 months.

Adjuvant chemotherapeutic regimens have been studied in high-risk endometrial cancers, but none have demonstrated a survival advantage. Doxorubicin, in combination with platinum, has a reported 42% response rate, but a high toxicity profile. Paclitaxel has an overall response rate of 36% in patients with advanced and recurrent endometrial cancer. Platinum-based chemotherapies have a 28-42% response rate.

Retrospective studies in patients with UPSC have demonstrated response rates of up to 35% in patients with multiagent chemotherapy. In one study, a median progression-free interval of 30 months was observed in patients treated with paclitaxel and platinum in the adjuvant and recurrent settings. Based on these findings and the similarities and clinical success of paclitaxel/platinum therapy in patients with ovarian serous carcinoma, this combination warrants further investigation in a prospective manner in patients with UPSC.

Combination chemo/radiotherapy trials in advanced/recurrent endometrial cancer are ongoing. The optimal radiation modality, chemotherapeutic agents, and sequence of these regimens for the treatment of UPSC are yet to be established. A retrospective review of 16 patients treated at our institution with the sequential use of radiation "sandwiched" between paclitaxel/platinum chemotherapy found only one patient to have recurred at 16 months with a median follow-up of 15 months (range 6-33 months). The regimen was well tolerated. Eight of the sixteen patients (50%) developed grade 3 neutropenia following cycle 4 of chemotherapy, two of which required a 1 week treatment delay. There were no cases of grade 3 or 4 thrombocytopenia noted. There was no febrile neutropenia and no hospital admissions for toxicity. There were no observed grade 3 or 4 non-hematologic toxicities. With the median follow up of 15 months, we have not observed late toxicities.

Given these favorable preliminary findings, supported by recently published data documenting efficacy of the "sandwich" multimodality technique in other difficult uterine malignancies (malignant mixed mullerian tumors), we propose to study this combination of chemotherapy and radiation prospectively. Our aim is to better evaluate patterns of recurrence and possible benefits in progression-free and overall survival.

Surrogate endpoint biomarkers such as ER/PR, HER2/Neu and p53 will be correlated with prognosis. In addition, fresh frozen tissue will be banked for future cDNA microarray analyses of UPSC tumors.

A Study of Radiation Therapy and Paclitaxel and Carboplatin in Patients With Uterine Papillary Serous Carcinoma

A Pilot Phase II Trial of Radiation Therapy "Sandwiched" Between Paclitaxel and Carboplatin in Patients With Uterine Papillary Serous Carcinoma

Overall survival analysis of early stage (stage 1 \& 2) and late stage (stage 3 \& 4)UPSC patients who were prescribed radiation "sanwhiched" between three cycles of paclitaxel/platinum chemotherapy before and after RT. Outcome measures were Progression Free Survival (PFS) and Overall Survival (OS).

Montefiore Medical Center

Attending

There is no difference in the reporting of adverse events. Adverse even data is not available. Only the toxicity data are available.

Drug:Carboplatin and Paclitaxel and Radiation: Pelvic Radiation Therapy

Carboplatin and Paclitaxel and Pelvic Radiation Therapy : Paclitaxel 175 mg/m2/3 hour \& Carboplatin (AUC=6.5) Repeat q 21 days x 3 cycles followed by RT followed by Paclitaxel 175 mg/m2/3 hour \& Carboplatin (AUC=5.0)Repeat q 21 days x 3 cycles

Note: The original PI has left the institution, therefore Dr. Kuo inherited the study. Efforts were made to contact the PI/study team members to locate the raw data, but were unsuccessful. No AE data are available at this time.

Carboplatin & Paclitaxel & Radiation: Pelvic Radiation Therapy

Drug:Carboplatin and Paclitaxel and Radiation: Pelvic Radiation Therapy

Carboplatin and Paclitaxel and Pelvic Radiation Therapy : Paclitaxel 175 mg/m2/3 hour \& Carboplatin (AUC=6.5) Repeat q 21 days x 3 cycles followed by RT followed by Paclitaxel 175 mg/m2/3 hour \& Carboplatin (AUC=5.0)Repeat q 21 days x 3 cycles

Carboplatin and Paclitaxel and Radiation Therapy : Paclitaxel 175 mg/m2/3 hour \& Carboplatin (AUC=6.5) Repeat q 21 days x 3 cycles followed by RT followed by Paclitaxel 175 mg/m2/3 hour \& Carboplatin (AUC=5.0)Repeat q 21 days x 3 cycles

Drug:Carboplatin, Paclitaxel & Radiation

We considered 72 patients as baseline participants because they are the ones who completed the first three cycles of chemotherapy followed by at least partial RT. Of the 72 patients, 65 of them completed all prescribed regimen of treatment. This was the reason for the discrepancy.

There are minor differences in the carboplatin doses between the current trial and our pilot study.

This is a single institution trial. A limited number of advanced stage patients was accrued.

Dr. Dennis Yi-Shin Kuo

Early stage (PFS)

Late stage (PFS)

Early stage (OS)

Late stage (OS)

Drug:Carboplatin and Paclitaxel and Radiation: Pelvic Radiation Therapy

Carboplatin and Paclitaxel and Pelvic Radiation Therapy: Paclitaxel 175 mg/m2/3 hour \& Carboplatin (AUC=6.5) Repeat q 21 days x 3 cycles followed by RT followed by Paclitaxel 175 mg/m2/3 hour \& Carboplatin (AUC=5.0)Repeat q 21 days x 3 cycles

Carboplatin and Paclitaxel and Radiation Therapy: Paclitaxel 175 mg/m2/3 hour \& Carboplatin (AUC=6.5) Repeat q 21 days x 3 cycles followed by RT followed by Paclitaxel 175 mg/m2/3 hour \& Carboplatin (AUC=5.0)Repeat q 21 days x 3 cycles

Kaplan-Meier survival analysis of Progression Free Survival (PFS) and Overall Survival (OS).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Gleevec/Taxol for Patients With Uterine Papillary Serous Carcinoma	NCT00506779	Uterine Cancer	Imatinib Mesyla... Paclitaxel	-	M.D. Anderson Cancer Center
A Study of Radiation Therapy and Paclitaxel and Carboplatin in Patients With Uterine Papillary Serous Carcinoma	NCT00231868	Uterine Cancer	Carboplatin and... Carboplatin and... Carboplatin and...	18 Years -	Montefiore Medical Center

Spots Global Cancer Trial Database for upsc

Every month we try and update this database with for upsc cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for upsc

Every month we try and update this database with for upsc cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for upsc cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.