Clinical trial NCT02124421: HOT: HIPEC in Ovarian Cancer as Initial Treatment
Official title: Phase II Randomized Study: Cytoreductive Surgery (CRS) With/Without Carboplatin Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Followed by Adjuvant Chemotherapy as Initial Treatment of Ovarian, Fallopian Tube, & Primary Peritoneal Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Stage III Ovarian Cancer
Stage IV Ovarian Cancer
Epithelial Ovarian Cancer
Fallopian Tube Cancer
Primary Peritoneal Carcinoma
Ovarian Carcinoma
Fallopian Tube Carcinoma
Keywords: Ovarian cancer
Cytoreductive surgery
Hyperthermic Intraperitoneal chemotherapy
Systemic chemotherapy
Primary peritoneal carcinoma
Fallopian Tube cancer
Intraperitoneal chemotherapy
IV/IP chemotherapy
IV chemotherapy
Lead sponsor: Mercy Medical Center
Sponsor class: OTHER
First posted: 2014-04-28
Enrollment: 32
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Community hospital based phase II (prospective randomized) study to evaluate the toxicity of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in newly diagnosed, otherwise untreated, advanced stage (stage III/IV) epithelial ovarian, fallopian tube, and primary peritoneal cancer.

Detailed description: Primary endpoints:

* To assess the feasibility of recruitment
* Compare complication rates between the two study arms: CRS with HIPEC and CRS alone.

Secondary endpoints:

* To determine risk factors for morbidity and mortality
* Assess completion rate of 6 cycles of systemic chemotherapy
* To determine progression free survival at 24 months
* To determine overall survival at 1, 3, and 5 years
* Evaluate health related quality of life

Patients who meet study criteria will be randomized into one of two treatment arms: 1) cytoreductive surgery (CRS) with carboplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) followed by IV combination chemotherapy with carboplatin and paclitaxel or 2) cytoreductive surgery (CRS) alone followed by adjuvant intraperitoneal (IP) and IV chemotherapy with combination cisplatin and paclitaxel for newly diagnosed advanced stage (stage III/IV) ovarian, fallopian tube or primary peritoneal cancer. Both study arms will receive 6 cycles of adjuvant chemotherapy.

Twenty-four patients will undergo CRS with HIPEC performed by surgical and gynecologic oncologic surgeons at Mercy Medical Center, followed by systemic IV chemotherapy with carboplatin (AUC=6) and paclitaxel (175mg/m2) for 6 cycles postoperatively.

Twenty-four patients will undergo CRS only performed by surgical and gynecologic oncologic surgeons at Mercy Medical Center, followed by IV/IP chemotherapy with Day 1: IV paclitaxel (135 mg/m2), Day 2: IP cisplatin (75 mg/m2), and Day 8: IP paclitaxel (60 mg/m2) for 6 cycles postoperatively.

Eligibility criteria: Inclusion Criteria:

* Clinical presentation of ovarian, fallopian tube or primary peritoneal cancer
* Stage III/IV disease
* No prior treatment or significant surgery for the management of ovarian, fallopian tube, or primary peritoneal carcinoma; History of laparoscopic procedures to obtain diagnostic biopsies will be permitted in the study
* Histological confirmation
* Eastern Cooperative Oncology Group performance status 0-2 or Karnofsky performance status ≥ 70%
* ≤1 cm residual disease at the completion of the cytoreductive surgery (GOG criteria for optimally cytoreduction)
* Bone marrow function:

  1. Absolute neutrophil count (ANC) ≥1,000/mm3
  2. Platelets ≥100,000/mm3
  3. Hemoglobin ≥ 8.5 g/dL
* Renal function:

  1) Creatinine ≤1.5 times the upper limit of normal or a calculated creatinine clearance ≥60ml/min
* Hepatic function:

  1. Bilirubin ≤1.5 times upper limit of normal
  2. Alanine aminotransferase (ALT) ≤3 times upper limit of normal
  3. Aspartate aminotransferase (AST) ≤3 times upper limit of normal
* Blood coagulation parameters:

  1. Prothrombin time (PT) with International Normalized Ratio of ≤1.5 and a partial prothrombin time (PTT) ≤1.5 times upper limit of normal
  2. For patients on full dose warfarin, in range International Normalized Ratio (usually between 2 and 3) and
  3. Partial prothrombin time (PTT) \<1.2 times upper limit of normal
  4. Candidate for administration of postoperative standard platinum-based combination systemic chemotherapy (adequate bone marrow, renal, hepatic function, and blood coagulation parameters)

Exclusion Criteria:

* Any prior treatment modality for the diagnosis of ovarian, fallopian tube, or primary peritoneal cancerPrior surgical attempt of cytoreductive surgery
* Stage I/II disease
* Presence of other invasive malignancies or evidence of other cancer within the past 3 years
* Known active acute hepatitis and confirmed diagnosis of HIV
* Active systemic infection that requires use of parenteral antibiotics
* History of acute coronary syndromes (ACS), within the last 6 months, according to AHA definitions
* New York Heart Association (NYHA) Class II or higher congestive heart failure according to American Heart Association (AHA) definitions
* Canadian Cardiovascular Society (CCS) Class II or higher angina grade according to AHA definitions
* Uncontrolled hypertension defined as \> 140/90 and not cleared for surgery at time of consent by cardiologist
* History of cerebral artery disease and prior stroke according to AHA definitions in the last 6 months
* Renal insufficiency with serum creatinine level ≥1.5 times the upper limit of normal or calculated creatinine clearance \<60 ml/min
* Patients with concurrent severe medical problems unrelated to malignancy that will preclude compliance with the study or places at an unacceptable risk for participation in the study determinate by study investigators
* Pregnant women are excluded from this study because carboplatin is category D agent with the potential of teratogenic effects. Due to potential risk for adverse events in nursing infants secondary to treatment of the mother with carboplatin, breastfeeding should be discontinued
* Life expectancy of \< 12 weeks

Primary outcomes:
measure: Post-operative complication rates
timeFrame: 30 days post-operative
Secondary outcomes:
measure: Assessment of quality of life
timeFrame: Baseline, 4 weeks post-operative, upon completion of systemic chemotherapy, and years 1, 2, 3, 4, & 5
measure: Evaluate the rate of progression free survival
timeFrame: at 24 months
measure: Evaluate overall survival
timeFrame: at 1, 3, and 5 years
Other outcomes:
measure: Risk factors for morbidity and mortality
timeFrame: During & at study completion
Locations:
city: Baltimore
country: United States
facility: Mercy Medical Center
state: Maryland
Study officials:
affiliation: Mercy Medical Center
name: Teresa Diaz-Montes, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Mercy Medical Center
name: Armando Sardi, M.D.
role: PRINCIPAL_INVESTIGATOR
References: