Fallopian Tube Cancer, Ovarian Cancer, Peritoneal Carcinoma
Conditions
Keywords
recurrent ovarian cancer, recurrent fallopian tube cancer, recurrent peritoneal carcinoma
Brief summary
This is an open-label, pilot study in patients with a diagnosis of recurrent ovarian, fallopian tube or primary peritoneal carcinoma who have undergone standard cytoreductive surgery following by adjuvant chemotherapy. It is expected that this first surgery was optimal - as defined as no residual tumor \> or = 1 centimeter. Patient has clinical evidence of a first recurrence. The patient undergoes surgery and isotonic normal saline (perfusate) heated and administered into the abdomen, followed by hyperthermic intraperitoneal chemotherapy infusion (HIPC) administering carboplatin (chemotherapy). Six weeks after surgery patients will receive adjuvant chemotherapy with Paclitaxel and Carboplatin for 6 cycles.
Detailed description
OBJECTIVES * The primary objectives are * to determine the clinical response of hyperthermic intraperitoneal chemotherapy (HIPC) in patients at the time of first clinical recurrence of ovarian, fallopian tube, or primary peritoneal carcinoma * to determine the feasibility of delivering HIPC in a recurrent setting. * Secondary objectives are * to determine disease free survival (DFS) and overall survival (OS), * to determine treatment related changes in quality of life (QOL) * to monitor the toxicities and complications associated with HIPC.
Interventions
DRUGHyperthermic intraperitoneal chemotherapy with Carboplatin
Carboplatin at a dose of 1000mg/m\^2 will be added to the perfusate once circulating levels reach 1000-1500cc/minute. The circulation of the chemotherapy impregnated perfusate will be performed for 90 minutes.
OTHERIsotonic saline (perfusate)
The HIPC infusion will be performed with a closed abdomen technique. The perfusate will be isotonic saline heated to 40-42° Celsius.
PROCEDURESurgery
The abdominal incision will be performed in a vertical fashion extending from the supra-pubic region to around the umbilicus. If cytoreductive surgery is required, it will be performed at this time and proceed in standard approach.
DRUGCarboplatin
The scheduled systemic chemotherapy is paclitaxel 175mg/m2 and carboplatin AUC 6 every 3 weeks for 6 total cycles.
DRUGPaclitaxel
The scheduled systemic chemotherapy is paclitaxel 175mg/m2 and carboplatin AUC 6 every 3 weeks for 6 total cycles.
Sponsors
Masonic Cancer Center, University of Minnesota
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
16 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Patients should have a histological diagnosis of primary ovarian, fallopian tube, or primary peritoneal carcinoma and have undergone chemotherapy according. * Initial attempted cytoreductive surgery must have been performed by gynecologic oncologist with strict adherence to GOG surgical manual. * End result of first surgery must have been optimal cytoreduction as defined as no residual tumor ≥ 1cm. * Patients should have clinical evidence of first recurrence. Two fold elevations in CA125 or measurable tumor on CT scan constitute adequate evidence of recurrent disease. * Patients with the following primary tumor epithelial cell types are eligible: serous adenocarcinoma, endometrioid adenocarcinoma, mucinous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, adenocarcinoma (non-specific) NOS, mixed epithelial carcinoma. * Patients must have platin sensitive disease, defined as a recurrence occurring greater than 6 months from cessation of original treatment. * Patients must have a performance status of 0, 1, 2. * Patients must have adequate bone marrow function as defined by an absolute neutrophil count (ANC) ≥1500, platelet count ≥ 100,000, and a hemoglobin of greater than 10g/dl. * Patients must have adequate renal function as defined by serum creatinine ≤ 1.5 mg/dl. * Patients must have adequate hepatic function as defined by bilirubin ≤ 1.5 times normal levels, alkaline phosphatase and SGOT ≤ 3 times normal levels. * Patients who have signed an Institutional Review Board (IRB) approved informed consent. * Female patients 16-90 years of age. * Patients must be deemed medically able to undergo a secondary surgical procedure. Patient eligibility for systemic chemotherapy following HIPC: * Patients must have successfully completed HIPC within 6 weeks of first prescribed intravenous carboplatin and taxane cycle. * Patients must have a performance status of 0, 1, or 2. * Patients must have adequate bone marrow function as defined as an ANC ≥ 1500, platelet count ≥ 100,000, and a hemoglobin of greater than 10g/dl. * Patients must have adequate renal function as defined by serum creatinine ≤ 1.5 mg/dl. * Patients must have adequate hepatic function as defined by bilirubin ≤ 1.5 times normal levels, alkaline phosphatase and SGOT ≤ 3 times normal levels. * Patients who have signed an IRB approved informed consent.
Exclusion criteria
* Patients with known recurrent disease outside the abdominal cavity. * Patients with low malignant tumor at primary diagnosis as determined by pathologic review. * Patients with platin resistant disease as define as recurrence or progressive disease prior to 6 months from completion of primary therapy. * Patients with any evidence of another malignancy within the last 5 years with the exception of non-melanoma skin cancer. * Patients with evidence of concurrent septicemia, severe infection, renal failure, or acute hepatitis. * Patients with history of grade 3 or greater gastrointestinal bleeding. * Patients with a GOG performance score of 3 or 4. * Patients deemed medically unable to tolerate the HIPC procedure by care giving physician. * Patients with known allergy to platinum chemotherapy agents. * Patients with equal to or greater than grade 2 neuropathy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Response | After 6 cycles of Paclitaxel & Carboplatin (Week 21 up to 27) | We will summarize clinical response as the proportion of patients with complete response. Complete response will be defined as normalization of CA125. - After 6 cycles of Second Line Adjuvant Chemotherapy. |
| Feasibility of HIPC in Recurrent Disease Setting | 6 months | We will determine feasibility based on the proportion of patients who complete 6 prescribed cycles of second line chemotherapy after undergoing the HIPC procedure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quality of Life Measurements | Baseline, 6 Weeks Post Surgery, Every 3 Weeks Up to Week 27 | The quality of life measurements (version 4 of the FACT-O questionnaire) will be summed over each subscale and overall and comparisons will be made using t-tests at distinct visits. |
| Progression-free Survival | Up to 5 Years (intended) | Disease progression will be defined as time from surgery to first of either an increase in CA125 from post-treatment value (to a value greater than 100 or doubling of nadir CA125 levels) or new/increasing measurable disease by CT scan as defined by RECIST criteria, (secondary recurrence) or censored at date of last contact for patients still alive and who have no progressed or recurred (from date of surgery to disease progression). |
| Overall Survival | Up to 5 Years | Overall survival will be defined as time from date of surgery to date of death or censored at the date of last documented contact for patients still alive. |
Countries
United States
Participant flow
Recruitment details
Women were recruited from the Women's Health Clinic at the University of Minnesota. Recruitment occurred from September 2010 to April 2012.
Pre-assignment details
Once subjects signed consent, they underwent cytoreductive surgery by a gynecologic oncologist with intent to resect all visible cancer. If subjects did not achieve optimal cytoreduction, they were ineligible.
Participants by arm
| Arm | Count |
|---|---|
| HIPC Treatment Patients treated with hyperthermic intraperitoneal chemotherapy at first recurrence of disease. | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | HIPC Treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants |
| Age, Customized | 56 years FULL_RANGE 16.7 |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 10 / 10 |
| serious Total, serious adverse events | 2 / 10 |
Outcome results
Primary
Clinical Response
We will summarize clinical response as the proportion of patients with complete response. Complete response will be defined as normalization of CA125. - After 6 cycles of Second Line Adjuvant Chemotherapy.
Time frame: After 6 cycles of Paclitaxel & Carboplatin (Week 21 up to 27)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HIPC Treatment | Clinical Response | 10 participants |
Primary
Feasibility of HIPC in Recurrent Disease Setting
We will determine feasibility based on the proportion of patients who complete 6 prescribed cycles of second line chemotherapy after undergoing the HIPC procedure.
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HIPC Treatment | Feasibility of HIPC in Recurrent Disease Setting | 9 participants |
Secondary
Overall Survival
Overall survival will be defined as time from date of surgery to date of death or censored at the date of last documented contact for patients still alive.
Time frame: Up to 5 Years
Population: Data was not collected due to the trial and all data collection processes being being terminated.
Secondary
Progression-free Survival
Disease progression will be defined as time from surgery to first of either an increase in CA125 from post-treatment value (to a value greater than 100 or doubling of nadir CA125 levels) or new/increasing measurable disease by CT scan as defined by RECIST criteria, (secondary recurrence) or censored at date of last contact for patients still alive and who have no progressed or recurred (from date of surgery to disease progression).
Time frame: Up to 5 Years (intended)
Population: Data was not collected due to the trial and all data collection processes being being terminated.
Secondary
Quality of Life Measurements
The quality of life measurements (version 4 of the FACT-O questionnaire) will be summed over each subscale and overall and comparisons will be made using t-tests at distinct visits.
Time frame: Baseline, 6 Weeks Post Surgery, Every 3 Weeks Up to Week 27
Population: Data was not collected due to the trial and all data collection processes being being terminated.