Advanced Endometrial Adenocarcinoma, Stage III A, B, CPhase 2NCT00285415
A Phase II Evaluation of Docetaxel and Carboplatin Followed by Tumor Volume Directed Pelvic Irradiation
A Phase 2 study testing Docetaxel and Carboplatin in people with Advanced Endometrial Adenocarcinoma, Stage III A, B, C, run by Carilion Clinic at 2 sites in United States.
Trial summary
The purpose of this study is to determine the effectiveness of the combination of the two drugs, docetaxel (Taxotere®) and carboplatin (Paraplatin®) followed by radiation directed at the tumor in treating your endometrial cancer. Read more about this study
- Who is it for?
- Ages 18 to 99 years, women only
- Conditions the study is for
- Advanced Endometrial Adenocarcinoma, Stage III A, B, C
- What is being tested?
- Docetaxel and Carboplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 2 sitesUnited States
- Study dates
- Apr 2005to Jun 2012
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 to 99 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All patients with advanced endometrial adenocarcinoma, stage III A, B, C and Stage IV confined to the pelvis, and recurrent disease limited to the pelvis.
- Surgical stage III and limited stage IV disease, including those patients with positive adnexa, tumor invading the serosa, positive and/or para-aortic nodes, pelvic metastases, positive pelvic washings or vaginal involvement.
- Histology must be adenocarcinoma, adenosquamous cell, squamous cell, clear cell or serous papillary carcinoma
- Status post surgical resection, including a hysterectomy and bilateral salpingo-oophorectomy within the past
- 6 weeks (Pelvic lymph node and para-aortic lymph node sampling are optional)
- Patients may be sub-optimally or optimally debulked (disease < 2 cm). Patients are eligible with measurable disease or evaluable
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- disease. All positive para-aortic node patients must be further staged by chest CT scan. If chest CT scan is negative, patients are eligible.
- Patients who have met the pre-entry criteria including following lab findings:
- ANC > 1500, Platelet count > 100,000/mm3, Hemoglobin ≥ 8 mg/dl, Creatinine < 2.0 mg/dl.
- Total Bilirubin must be within normal limits. (WNL)
- AST or ALT and Alkaline Phosphatase must be within the range allowing for eligibility
- Patients who have signed an approved informed consent.
- GOG Performance Grade 0, 1, or 2.
- Women ≥ 18 years of age
Who cannot join
- Patients with Stage IV or recurrent disease outside of the pelvis.
- Patients who have had prior pelvic or abdominal radiation therapy.
- Patients with concomitant malignancy other than non-melanoma skin cancer.
- Patient with a prior malignancy who have been disease-free for < 5 years or who received prior chemotherapy or radiation therapy for that malignancy.
- Patients with a history of serious co-morbid illness that would preclude protocol therapy.
- Patients with an estimated survival of less than three months.
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- Patients with parenchymal liver metastases.
- Patients who received prior chemotherapy excluding low-dose methotrexate for rheumatologic reasons.
- Histology consistent with uterine sarcomas, carcinosarcoma or leiomyosarcoma.
- Women with baseline peripheral neuropathy Grade ≥ 2.
- Women with a history of severe hypersensitivity reaction to drugs formulated with polysorbate 80.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Gynecologic Oncology Research & Development, LLC
Greenville, South Carolina, 29601
Carilion GYN Oncology Associates
Roanoke, Virginia, 24014
About this study
Official title: A Phase II Evaluation of Docetaxel and Carboplatin Followed by Tumor Volume Directed Pelvic Plus or Minus Para-Aortic Irradiation for Stage III/IV Endometrial Carcinoma
The purpose of this study is to determine the effectiveness of the combination of the two drugs, docetaxel (Taxotere®) and carboplatin (Paraplatin®) followed by radiation directed at the tumor in treating your endometrial cancer.
Read the detailed description
Endometrial carcinoma is the most common malignancy in the female reproductive tract. For the percentage of patients with advanced stage (III - IV) optimum adjuvant therapy status-post surgical staging and/or optimal cytoreductive surgery is not well defined and limited in the rates of response. Survival rates range from 18 - 49% with high levels of toxicity with the current treatment regimens.
The Gynecologic Oncology Group (GOG) explored the use of chemotherapy in protocol #107 comparing adriamycin with a combination of adriamycin and cisplatin. This trial boasted a 45% response rate for the combination arm compared to a 27% response rate in the adriamycin only arm. Although no difference was seen in overall survival, the combination arm showed an improvement in progression free survival from 3.8 to 5.7 months. Subsequently, GOG protocol #122 randomized patients to this chemotherapeutic regimen versus whole abdominal radiation therapy. This trial is now closed to accrual and results are pending.
Ball et. al. reported on a phase II trial of paclitaxel in advanced or recurrent endometrial cancer done through the GOG.(3) At 250 mg/m2 (200mg/m2 for patients with previous radiation therapy) over 24 hours, every 21 days, 10/28 patients responded. There were 4 complete responders and 6 partial responders with an overall response rate of 35.7%. Toxicity was remarkably high with grade 3 and 4 neutropenia and neurotoxicity seen in 62% and 10.7%, respectively.
Dimpoulos et. al. reported the use of paclitaxel 175 mg/m2 over 3 hours and cisplatin 75mg/m2 every 21 days in advanced or recurrent endometrial carcinoma.(4) A 67% objective response rate was seen with 29% showing a complete response and 38% partial response. Toxicities included a 9% grade 3 and 4 peripheral neuropathy rate. These response rates changed the standard of care in the community setting from the more toxic regimen of adriamycin and cisplatin to paclitaxel and carboplatin.
Hoskins et. al. substituted carboplatin for cisplatin in an effort to reduce the peripheral neuropathy seen in the Dimpoulos trial. This phase II combination of paclitaxel and carboplatin with radiation therapy in advanced endometrial cancer resulted in a 75% response rate. The median failure-free survival time was 23 months, with a 62% 3-year overall survival rate. Toxicities were primarily hematologic and reversible.
The ongoing GOG protocol, #184, is exploring the combination of tumor directed radiation followed by a randomization to adriamycin and cisplatin versus adriamycin, cisplatin and paclitaxel with G-CSF support. Increased toxicity will be expected in the three-drug regimen. With a significant response rates to a combination of paclitaxel and carboplatin along with radiation therapy in the phase II setting it is hard to justify the added toxicity of this three-drug regimen.
The SCOTROC phase III trial comparing docetaxel (75 mg/m2) over 1 hour plus carboplatin (AUC 6) vs. paclitaxel (175 mg/m2) over 3 hours plus carboplatin (AUC 6) yielded equivalent overall response rates in 1,077 patients with ovarian cancer. The docetaxel arm resulted in significantly less overall grade 2 and 3 sensory and motor neurotoxicity. Only 4 patients withdrew from the trial due to neurotoxicity on the docetaxel arm vs. 32 patients on the paclitaxel arm. However, the docetaxel arm resulted in a higher incidence of neutropenia and associated complications without compromising treatment delivery of overall safety.
Based on the information to date, it seems prudent to explore a phase II trial of docetaxel plus carboplatin every 3 weeks for 6 cycles followed by radiation therapy in the management of patients with advanced endometrial cancer. The proposed protocol design requires that chemotherapy be administered prior to radiation therapy in order to control distant metastatic disease before attempting to control for local-regional recurrences with radiation.
- Being tested
- Docetaxel and Carboplatin
- Keywords
- Advanced endometrial adenocarcinoma, stage III A, B, C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Docetaxel and CarboplatinDrug
docetaxel (75 mg/m2) + carboplatin (AUC 6) IV every 3 weeks X 6 cycles
| Study group | Role | What they receive |
|---|---|---|
| Doc and Car | Other | Receiving Doc and Car Receives: Drug: Docetaxel and Carboplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate (ORR) for patients treated with docetaxel and carboplatin as measured by RECIST 1.1
to estimate the overall response rate (ORR) for women with newly diagnosed stages III-IV or recurrent endometrial carcinoma treated with docetaxel and carboplatin followed by tumor volume directed pelvic plus or minus para-aortic irradiation.
Measured: every 3 months
Secondary outcomes (3)
Progressive free survival (PFS) for patients treated with docetaxel and carboplatin as measured by CA125.
To estimate the progressive free survival (PFS)
Measured: every 3 months for 2 years and then every 6 months for 3 years. Yearly after 5 years.
To estimate overall survival (OS)
To estimate overall survival (OS)
Measured: every 3 months for 2 years then every 6 months for 3 years
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Determine the safety and tolerability of docetaxel and carboplatin
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2006 (estimated)
- Study startApr 2005
- Primary completionApr 2012
- Study completionJun 2012
Why it stopped: Investigator abruptly left Carilion.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Endometrial Adenocarcinoma, Stage III A, B, CStudies of the same condition, open and under way.
- 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
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- Carilion Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- Sanofi
- Responsible party
- Sponsor
- Investigators
- Dennis R Scribner, JR, MD, Principal investigator
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00285415
- Sponsor's protocol ID
- EndoRT
- Other IDs
- WIRB PRO NUM: 20050247
- Status last verified
- Feb 2021
- First submitted
- 31 Jan 2006
- Last updated
- 5 Feb 2021
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Evaluation of Docetaxel and Carboplatin Followed by Tumor Volume Directed Pelvic Plus or Minus Para-Aortic Irradiation for Stage III/IV Endometrial Carcinoma
- ClinicalTrials.gov ID
- NCT00285415
- Acronym / sponsor ID
- EndoRT
- Keywords
- Advanced endometrial adenocarcinoma, stage III A, B, C
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Investigator abruptly left Carilion.
- Enrolment
- 46 participants (actual)
- Lead sponsor
- Carilion ClinicUniversity, hospital or other
- Collaborators
- Sanofi
- Study start
- Apr 2005 (actual)
- Primary completion
- Apr 2012 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 2 Feb 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the effectiveness of the combination of the two drugs, docetaxel (Taxotere®) and carboplatin (Paraplatin®) followed by radiation directed at the tumor in treating your endometrial cancer.
Detailed description
Endometrial carcinoma is the most common malignancy in the female reproductive tract. For the percentage of patients with advanced stage (III - IV) optimum adjuvant therapy status-post surgical staging and/or optimal cytoreductive surgery is not well defined and limited in the rates of response. Survival rates range from 18 - 49% with high levels of toxicity with the current treatment regimens.
The Gynecologic Oncology Group (GOG) explored the use of chemotherapy in protocol #107 comparing adriamycin with a combination of adriamycin and cisplatin. This trial boasted a 45% response rate for the combination arm compared to a 27% response rate in the adriamycin only arm. Although no difference was seen in overall survival, the combination arm showed an improvement in progression free survival from 3.8 to 5.7 months. Subsequently, GOG protocol #122 randomized patients to this chemotherapeutic regimen versus whole abdominal radiation therapy. This trial is now closed to accrual and results are pending.
Ball et. al. reported on a phase II trial of paclitaxel in advanced or recurrent endometrial cancer done through the GOG.(3) At 250 mg/m2 (200mg/m2 for patients with previous radiation therapy) over 24 hours, every 21 days, 10/28 patients responded. There were 4 complete responders and 6 partial responders with an overall response rate of 35.7%. Toxicity was remarkably high with grade 3 and 4 neutropenia and neurotoxicity seen in 62% and 10.7%, respectively.
Dimpoulos et. al. reported the use of paclitaxel 175 mg/m2 over 3 hours and cisplatin 75mg/m2 every 21 days in advanced or recurrent endometrial carcinoma.(4) A 67% objective response rate was seen with 29% showing a complete response and 38% partial response. Toxicities included a 9% grade 3 and 4 peripheral neuropathy rate. These response rates changed the standard of care in the community setting from the more toxic regimen of adriamycin and cisplatin to paclitaxel and carboplatin.
Hoskins et. al. substituted carboplatin for cisplatin in an effort to reduce the peripheral neuropathy seen in the Dimpoulos trial. This phase II combination of paclitaxel and carboplatin with radiation therapy in advanced endometrial cancer resulted in a 75% response rate. The median failure-free survival time was 23 months, with a 62% 3-year overall survival rate. Toxicities were primarily hematologic and reversible.
The ongoing GOG protocol, #184, is exploring the combination of tumor directed radiation followed by a randomization to adriamycin and cisplatin versus adriamycin, cisplatin and paclitaxel with G-CSF support. Increased toxicity will be expected in the three-drug regimen. With a significant response rates to a combination of paclitaxel and carboplatin along with radiation therapy in the phase II setting it is hard to justify the added toxicity of this three-drug regimen.
The SCOTROC phase III trial comparing docetaxel (75 mg/m2) over 1 hour plus carboplatin (AUC 6) vs. paclitaxel (175 mg/m2) over 3 hours plus carboplatin (AUC 6) yielded equivalent overall response rates in 1,077 patients with ovarian cancer. The docetaxel arm resulted in significantly less overall grade 2 and 3 sensory and motor neurotoxicity. Only 4 patients withdrew from the trial due to neurotoxicity on the docetaxel arm vs. 32 patients on the paclitaxel arm. However, the docetaxel arm resulted in a higher incidence of neutropenia and associated complications without compromising treatment delivery of overall safety.
Based on the information to date, it seems prudent to explore a phase II trial of docetaxel plus carboplatin every 3 weeks for 6 cycles followed by radiation therapy in the management of patients with advanced endometrial cancer. The proposed protocol design requires that chemotherapy be administered prior to radiation therapy in order to control distant metastatic disease before attempting to control for local-regional recurrences with radiation.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Doc and Car | Other | Drug: Docetaxel and CarboplatinReceiving Doc and Car |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- All patients with advanced endometrial adenocarcinoma, stage III A, B, C and Stage IV confined to the pelvis, and recurrent disease limited to the pelvis.
- Surgical stage III and limited stage IV disease, including those patients with positive adnexa, tumor invading the serosa, positive and/or para-aortic nodes, pelvic metastases, positive pelvic washings or vaginal involvement.
- Histology must be adenocarcinoma, adenosquamous cell, squamous cell, clear cell or serous papillary carcinoma
- Status post surgical resection, including a hysterectomy and bilateral salpingo-oophorectomy within the past
- 6 weeks (Pelvic lymph node and para-aortic lymph node sampling are optional)
Key exclusion criteria (11 listed)
- Patients with Stage IV or recurrent disease outside of the pelvis.
- Patients who have had prior pelvic or abdominal radiation therapy.
- Patients with concomitant malignancy other than non-melanoma skin cancer.
- Patient with a prior malignancy who have been disease-free for < 5 years or who received prior chemotherapy or radiation therapy for that malignancy.
- Patients with a history of serious co-morbid illness that would preclude protocol therapy.
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 |
|---|---|---|
| Docetaxel and Carboplatindocetaxel (75 mg/m2) + carboplatin (AUC 6) IV every 3 weeks X 6 cycles | Drug | Doc and Car |
Primary outcome
Overall response rate (ORR) for patients treated with docetaxel and carboplatin as measured by RECIST 1.1
Time frame: every 3 months
to estimate the overall response rate (ORR) for women with newly diagnosed stages III-IV or recurrent endometrial carcinoma treated with docetaxel and carboplatin followed by tumor volume directed pelvic plus or minus para-aortic irradiation.
3 secondary outcomes
Progressive free survival (PFS) for patients treated with docetaxel and carboplatin as measured by CA125.
Time frame: every 3 months for 2 years and then every 6 months for 3 years. Yearly after 5 years.
To estimate overall survival (OS)
Time frame: every 3 months for 2 years then every 6 months for 3 years
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: 5 years
Results and safety
The study was stopped early (reason given: Investigator abruptly left Carilion.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2021.
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.
Dennis R Scribner, JR, MD principal investigator
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Docetaxel and Carboplatin in people with Advanced Endometrial Adenocarcinoma, Stage III A, B, C, run by Carilion Clinic at 2 sites 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 14 inclusion and 11 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 5 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
The study was stopped early (reason given: Investigator abruptly left Carilion.). Results are not available in the source record.
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?
Overall response rate (ORR) for patients treated with docetaxel and carboplatin as measured by RECIST 1.1 (time frame: every 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Feb 2021.