Fallopian Tube Cancer, Recurrent Ovarian Cancer
Conditions
Keywords
Primary peritoneal
Brief summary
The primary objective of this study is to investigate the feasibility, tolerability and safety of surgical debulking and resection with heated intraoperative chemotherapy (HIPEC) followed by repeated intraperitoneal chemotherapy for treatment of recurrent ovarian, primary peritoneal, and fallopian tube carcinomas.
Detailed description
This is a phase II , open label, single center study of surgery followed by heated intraoperative cisplatin in patients with recurrent ovarian, primary peritoneal or fallopian tube cancers. Approximately twenty patients will receive surgery and intraoperative (hyperthermic) cisplatin followed by four consecutive courses of outpatient intraperitoneal cisplatin and doxorubicin given on days 1 and 8 during a 3 week cycle.
Interventions
DRUGCisplatin
Cisplatin (75 mg/m2) prepared in 2L normal saline.
DRUGDoxorubicin
Doxorubicin (25 mg flat dose) prepared in 500 ml dialysis fluid (glucose or icodextrin-based).
Sponsors
Columbia University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients must have histologically confirmed ovarian, primary peritoneal or fallopian tube carcinoma. 2. Patients must have measurable evidence of recurrent intraabdominal disease based on Computed tomography (CT scan) findings. 3. Patients must fulfill the following with regard to prior chemotherapy: 1. 4 weeks or greater since conclusion of prior chemotherapy; 2. Prior intraperitoneal chemotherapy with cisplatin is acceptable; and, 3. Prior systemic chemotherapy is acceptable. 4. Patients must have a Karnofsky Performance Status of \> 70% 5. Patients must have an estimated life expectancy of at least 16 weeks. 6. Patient assurance of study compliance and geographic proximity that allows for adequate follow-up. 7. Patients must have adequate organ function at the screening visit as defined by the following laboratory values: Absolute neutrophil count (ANC) ≥1.5 x 109/L Platelet count ≥100 x 109/L Hemoglobin ≥8 g/dL Albumin ≥ 2 g/dL Total Bilirubin ≤ 2.5 x ULN\* Alkaline phosphatase ≤ 3.0 x ULN\* Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x ULN Creatinine ≤ 1.5 x ULN 8. Patient must have signed informed consent 9. Patient must be at least 18 years of age 10. Following cytoreductive surgery, patient's residual disease should be no larger than 1cm to Receive HIPEC and continue with normothermic IP chemotherapy
Exclusion criteria
1. Have active peripheral neuropathy of Grade 2 or greater intensity, as defined by the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE; Version 4). 2. Have experienced myocardial infarction within 6 months prior to enrollment or have New York Hospital Association (NYHA) Class III or IV heart failure (see section 16.4), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. 3. Prior radiation therapy within 4 weeks of enrollment. 4. Have uncontrolled active systemic infection requiring therapy. 5. Have a history of allergic reaction attributable to compounds containing boron or mannitol or hypersensitivity reactions to drugs formulated with polysorbate 80. 6. Have had a serious concomitant systemic disorders (including oncologic emergencies) incompatible with the study (at the discretion of the investigator). 7. Have had a currently active second malignancy other than non-melanoma skin cancer or carcinoma in situ of the cervix are not to be registered. Patients who are not considered to have a currently active malignancy if they have completed therapy and are considered by their physician to be at less than 30% risk of relapse. 8. Have had any investigational agent within 4 weeks before enrollment into the study. 9. Have a history of a serious medical or psychiatric illness preventing informed consent or, in the opinion of the investigator, would make the patient a poor study candidate. 10. Evidence of extraabdominal metastasis on preinclusion thoracic computed tomography (CT) scans (i.e. brain or chest disease).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Event Rate and/or Laboratory Changes | 5 years | The adverse event rate and laboratory changes will be used to investigate the safety of surgical debulking with heated intraperitoneal chemotherapy (HIPEC) combined with repeated intraperitoneal chemotherapy. |
| Toxicity Rating Based on NCI Common Toxicity Criteria | Up to 5 years | Patients will be rated for toxicity prior to each cycle using the NCI Common Toxicity Criteria (NCICTC; see the CTCAE, Version 4.0). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Serum Ca-125 Nadir and/or CT Response (RECIST Criteria) | Up to 5 years (survival) | Efficacy of surgical resection with HIPEC combined with repeated intraperitoneal chemotherapy: The end point will be the objective response rate and progression-free survival as well as the overall survival, if feasible. We will analyze the time to serum Ca 125 nadir and/or CT response based on Recist criteria. |
| Kaplan-Meier Curves for Patient Overall Survival | Up to 5 years, survival | Kaplan-Meier analysis will be done using PROC LIFETEST in Statistical Application Software (SAS). |
Countries
United States
Participant flow
Recruitment details
Subjects were screened and enrolled during 10/23/2012 to 08/20/2013.
Participants by arm
| Arm | Count |
|---|---|
| Intraoperative Cisplatin Followed by IP Chemotherapy Intraoperative (hyperthermic) cisplatin followed by 4 courses of intraperitoneal cisplatin and doxorubicin given on days 1 & 8 during a 3 week cycle
Intraoperative (hyperthermic) cisplatin followed by IP Cisplatin; Doxorubicin: Cisplatin 75 mg/m2 at 40.5-42.5 Celsius intraoperatively administered; IP Cisplatin 75 mg/m2 (Day 1) week 1 followed by IP Doxorubicin 25 mg week 2 (day 8) for four sequential 3 week cycles; | 4 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Study Termination | 4 |
Baseline characteristics
| Characteristic | Intraoperative Cisplatin Followed by IP Chemotherapy |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Region of Enrollment United States | 4 participants |
| Sex: Female, Male Female | 4 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 | 0 / 4 |
| serious Total, serious adverse events | 1 / 4 |
Outcome results
Primary
Adverse Event Rate and/or Laboratory Changes
The adverse event rate and laboratory changes will be used to investigate the safety of surgical debulking with heated intraperitoneal chemotherapy (HIPEC) combined with repeated intraperitoneal chemotherapy.
Time frame: 5 years
Population: zero participants analyzed due to early termination of study
Primary
Toxicity Rating Based on NCI Common Toxicity Criteria
Patients will be rated for toxicity prior to each cycle using the NCI Common Toxicity Criteria (NCICTC; see the CTCAE, Version 4.0).
Time frame: Up to 5 years
Population: zero participants analyzed due to early termination of study
Secondary
Kaplan-Meier Curves for Patient Overall Survival
Kaplan-Meier analysis will be done using PROC LIFETEST in Statistical Application Software (SAS).
Time frame: Up to 5 years, survival
Population: zero participants analyzed due to early termination of study
Secondary
Time to Serum Ca-125 Nadir and/or CT Response (RECIST Criteria)
Efficacy of surgical resection with HIPEC combined with repeated intraperitoneal chemotherapy: The end point will be the objective response rate and progression-free survival as well as the overall survival, if feasible. We will analyze the time to serum Ca 125 nadir and/or CT response based on Recist criteria.
Time frame: Up to 5 years (survival)
Population: zero participants analyzed due to early termination of study