Uterine CancerPhase 2NCT00231868
A Study of Radiation Therapy and Paclitaxel and Carboplatin in Patients With Uterine Papillary Serous Carcinoma
A Phase 2 study testing Carboplatin and Paclitaxel and Pelvic Radiation Therapy and Carboplatin and Paclitaxel and Radiation Therapy in people with Uterine Cancer, run by Montefiore Medical Center at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Uterine Cancer
- What is being tested?
- Carboplatin and Paclitaxel and Pelvic Radiation Therapy and Carboplatin and Paclitaxel and Radiation Therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 81 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2001to Jul 2011
- 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
- Histologically documented uterine papillary serous carcinoma (UPSC) with no visible residual disease.
- Surgical staging to include total abdominal hysterectomy, bilateral salpingo-oophorectomy, peritoneal washings, and lymph node samplings.
- Age > 18 years.
- ECOG performance status of < 2.
- Written voluntary informed consent.
Who cannot join
- Patient has impairment of hepatic, renal or hematologic function as defined by the following baseline laboratory values:
- Serum SGOT and /or SGPT > 2.5 times the institutional upper limit of normal
- Total serum bilirubin > 1.5 mg/dl
- History of chronic or active hepatitis
- Serum creatinine > 2.0 mg/dl
- Platelets < 100,000/mm3
Show all 12Show fewer
- Absolute neutrophil count (ANC) < 1500/mm3
- Hemoglobin < 8.0 g/dl (the patient may be transfused prior to study entry)
- Patient has severe or uncontrolled concurrent medical disease (eg. uncontrolled diabetes, unstable angina, myocardial infarction within 6 months, congestive heart failure, etc.)
- Patient has been treated with myelosuppressive chemotherapy within three weeks prior to study entry.
- Patient with any prior chemotherapy or radiotherapy for pelvic malignancy.
- Patients with dementia or altered mental status that would prohibit the giving and understanding of informed consent at the time of study entry.
Trial locations and contacts
1 site in 1 country.
United States1 site
Montefiore Medical Center
The Bronx, New York, 10461
About this study
Official title: A Pilot Phase II Trial of Radiation Therapy "Sandwiched" Between Paclitaxel and Carboplatin in Patients With Uterine Papillary Serous Carcinoma
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.
Read the detailed description
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.
- Conditions
- Uterine Cancer
- Being tested
- Carboplatin and Paclitaxel and Pelvic Radiation Therapy, Carboplatin and Paclitaxel and Radiation Therapy
- Keywords
- Uterine Papillary Serous Carcinoma, UPSC, Radiation Therapy, Chemotherapy
- Medical subject headings
- Uterine Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Carboplatin and Paclitaxel and Pelvic Radiation TherapyDrug
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 TherapyProcedure or surgery
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 TherapyDrug
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
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | Drug:Carboplatin and Paclitaxel and Radiation: Pelvic Radiation Therapy Receives: Drug: Carboplatin and Paclitaxel and Pelvic Radiation Therapy; Procedure: Carboplatin and Paclitaxel and Pelvic Radiation Therapy; Drug: Carboplatin and Paclitaxel and Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
To Evaluate the Toxicity and Tolerability of Pelvic Radiation "Sandwiched" Between Cycles of Paclitaxel/Carboplatin Chemotherapy in Patients With UPSC
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).
Measured: Up to 7 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2005 (estimated)
- Study startDec 2001
- Primary completionJul 2011
- Study completionJul 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Uterine CancerStudies of the same condition, open and under way.
- More trials run by Montefiore Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 81 participants (actual)
Sponsor and investigators
- Lead sponsor
- Montefiore Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dennis Yi-Shin Kuo, Montefiore Medical Center
- Investigators
- Mark H Einstein, M.D., M.S., Principal investigator, Montefiore Medical Center and Albert Einstein College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00231868
- Sponsor's protocol ID
- 01-09-227
- Status last verified
- Aug 2020
- First submitted
- 3 Oct 2005
- Last updated
- 12 Aug 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Einstein MH, Frimer M, Kuo DY, Reimers LL, Mehta K, Mutyala S, Huang GS, Hou JY, Goldberg GL. Phase II trial of adjuvant pelvic radiation "sandwiched" between combination paclitaxel and carboplatin in women with uterine papillary serous carcinoma. Gynecol Oncol. 2012 Jan;124(1):21-5. doi: 10.1016/j.ygyno.2011.10.007. Epub 2011 Oct 27.
PubMed 22035806
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Phase II Trial of Radiation Therapy "Sandwiched" Between Paclitaxel and Carboplatin in Patients With Uterine Papillary Serous Carcinoma
- ClinicalTrials.gov ID
- NCT00231868
- Acronym / sponsor ID
- 01-09-227
- Conditions
- Uterine Cancer
- Keywords
- Uterine Papillary Serous Carcinoma, UPSC, Radiation Therapy, Chemotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 81 participants (actual)
- Lead sponsor
- Montefiore Medical CenterUniversity, hospital or other
- Study start
- Dec 2001
- Primary completion
- Jul 2011 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 4 Oct 2005 (estimated)
- Results
- Posted 12 Aug 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Drug: Carboplatin and Paclitaxel and Pelvic Radiation Therapy, Procedure: Carboplatin and Paclitaxel and Pelvic Radiation Therapy, Drug: Carboplatin and Paclitaxel and Radiation TherapyDrug:Carboplatin and Paclitaxel and Radiation: Pelvic Radiation Therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Histologically documented uterine papillary serous carcinoma (UPSC) with no visible residual disease.
- Surgical staging to include total abdominal hysterectomy, bilateral salpingo-oophorectomy, peritoneal washings, and lymph node samplings.
- Age > 18 years.
- ECOG performance status of < 2.
- Written voluntary informed consent.
Key exclusion criteria (12 listed)
- Patient has impairment of hepatic, renal or hematologic function as defined by the following baseline laboratory values:
- Patient has severe or uncontrolled concurrent medical disease (eg. uncontrolled diabetes, unstable angina, myocardial infarction within 6 months, congestive heart failure, etc.)
- Patient has been treated with myelosuppressive chemotherapy within three weeks prior to study entry.
- Patient with any prior chemotherapy or radiotherapy for pelvic malignancy.
- Patients with dementia or altered mental status that would prohibit the giving and understanding of informed consent at the time of study entry.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Carboplatin and Paclitaxel and Pelvic Radiation TherapyPaclitaxel 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 | A |
| Carboplatin and Paclitaxel and Pelvic Radiation TherapyPaclitaxel 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 | Procedure or surgery | A |
| Carboplatin and Paclitaxel and Radiation TherapyPaclitaxel 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 | A |
Primary outcome
To Evaluate the Toxicity and Tolerability of Pelvic Radiation "Sandwiched" Between Cycles of Paclitaxel/Carboplatin Chemotherapy in Patients With UPSC
Time frame: Up to 7 years
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).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22035806Einstein MH, Frimer M, Kuo DY, Reimers LL, Mehta K, Mutyala S, Huang GS, Hou JY, Goldberg GL. Phase II trial of adjuvant pelvic radiation "sandwiched" between combination paclitaxel and carboplatin in women with uterine papillary serous carcinoma. Gynecol Oncol. 2012 Jan;124(1):21-5. doi: 10.1016/j.ygyno.2011.10.007. Epub 2011 Oct 27.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark H Einstein, M.D., M.S. principal investigator
Montefiore Medical Center and Albert Einstein College of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Carboplatin and Paclitaxel and Pelvic Radiation Therapy and Carboplatin and Paclitaxel and Radiation Therapy in people with Uterine Cancer, run by Montefiore Medical Center 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 5 inclusion and 12 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: finished, as of the sponsor's last update on 12 Aug 2020. 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 12 Aug 2020). 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?
To Evaluate the Toxicity and Tolerability of Pelvic Radiation "Sandwiched" Between Cycles of Paclitaxel/Carboplatin Chemotherapy in Patients With UPSC (time frame: Up to 7 years). 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 NCT00231868, which also lists 1 linked publication.
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 12 Aug 2020.