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Pilot / Phase III Randomized Trial Comparing Standard Systemic Therapy to Cytoreduction + Hyperthermic Intraperitoneal Mitomycin C + Standard Systemic Therapy in Patients With Limited Peritoneal Dissemination of Colon Adenocarcinoma


Phase 3
18 Years
N/A
Open (Enrolling)
Both
Colorectal Cancer

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Trial Information

Pilot / Phase III Randomized Trial Comparing Standard Systemic Therapy to Cytoreduction + Hyperthermic Intraperitoneal Mitomycin C + Standard Systemic Therapy in Patients With Limited Peritoneal Dissemination of Colon Adenocarcinoma


OBJECTIVES:

Primary

- To compare the overall survival (OS) of patients with advanced limited peritoneal
dissemination of colon adenocarcinoma treated with systemic therapy with vs without
cytoreduction surgery and hyperthermic intraperitoneal mitomycin C.

- To compare the relative OS at 1 year of patients treated with these regimens.

Secondary

- To compare the progression-free survival (PFS) of patients treated with these regimens.

- To compare the relative PFS at 1 year of patients treated with these regimens.

- To compare the quality of life of patients treated with these regimens.

- To compare the toxicity burden of these regimens in these patients.

- To compare the OS and PFS according to patients' peritoneal surface tumor genotype for
the NAD(P)H (quinone oxidoreductase 1 [NQO1] 609C >T polymorphism [wild type vs
heterozygous/homozygous mutant]) in patients treated with these regimens.

- To compare circulating tumor cells in patients treated with these regimens.

OUTLINE: This is a multicenter study. Patients are stratified according to presentation
(synchronous vs metachronous carcinomatosis), ECOG performance status (0 vs 1), disease
volume (measurable vs non-measurable), prior first-line therapy for advanced disease
(chemo-naïve vs prior first-line therapy), planned chemotherapy (oxaliplatin vs irinotecan
vs fluorouracil/leucovorin calcium vs capecitabine), and planned biologic therapy
(bevacizumab vs cetuximab vs none). Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive standard systemic therapy, at the discretion of patients'
oncologist, comprising combinations of fluorouracil, leucovorin calcium, irinotecan
hydrochloride, oxaliplatin, and/or capecitabine (including FOLFOX4, mFOLFOX6, CapeOx,
or FOLFIRI) with or without bevacizumab (beginning 4-6 weeks after major surgery) or
cetuximab*. Treatment repeats in the absence of disease progression or unacceptable
toxicity. Patients with progressive disease may crossover to arm II.

NOTE: *For patients with KRAS wild-type tumors.

- Arm II: Patients undergo cytoreduction surgery and hyperthermic intraperitoneal
mitomycin C over 45-90 minutes. Beginning 8 weeks after surgery, patients receive
standard systemic therapy as in arm I. Treatment with systemic therapy repeats for 6
courses in the absence of disease progression or unacceptable toxicity.

Blood and tissue samples may be collected from patients for correlative studies.

Patients complete SF-36 Health Survey; Functional Assessment of Cancer Therapy-Colorectal
(FACT-C); Feeling Sad, Down, or Depressed (CES-D); and a Brief Pain Inventory
quality-of-life questionnaires at baseline and then periodically during study.

After completion of study therapy, patients are followed up periodically for 5 years.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed colon adenocarcinoma meeting the following
criteria:

- Newly diagnosed disease

- Advanced disease

- Confirmed synchronous or metachronous limited peritoneal disease dissemination

- No appendiceal or rectal cancer

- No signet ring cell type

- Disease amenable to complete cytoreduction surgery as indicated by:

- Peritoneal Cancer Index (PCI) ≤ 20 by helical CT scan and/or staging laparoscopy

- No parenchymal hepatic metastases

- No clinical (jaundice), biochemical (abnormally elevated serum bilirubin and/or
alkaline phosphatase), or radiological (by ultrasound, CT scan, or MRI) biliary
obstruction

- No symptomatic malignant ascites requiring palliative paracentesis

- Small volume of disease in the gastro-hepatic ligament defined by a < 5 cm mass
in the epigastric region on cross-sectional imaging

- No cross-sectional imaging findings indicative of multi-segmental (> 1 site)
small bowel obstruction, small bowel loops matted together, or gross disease of
the small bowel mesentery characterized by distortion, thickening, or loss of
mesenteric vascular clarity

- No clinical or radiological evidence of hematogenous or distant nodal
(retroperitoneal, pelvic, mediastinal, peri-portal, or peri-aortic) metastasis

PATIENT CHARACTERISTICS:

- ECOG performance status 0-1

- ANC > 1,200/mm³

- WBC > 4,000/mm³

- Platelet count 150,000/mm³

- INR ≤ 1.5

- Patients on therapeutic anticoagulant for unrelated medical condition such as
atrial fibrillation or anti-thrombocyte treatment allowed provided treatment can
be withheld for operation

- Total serum bilirubin ≤ 1.5 mg/dL (> 1.5 mg/dL for patients with Gilbert syndrome)

- Alkaline phosphatase < 2.5 times upper limit of normal (ULN)

- AST < 1.5 times ULN

- Serum creatinine normal

- BUN normal

- Not pregnant or nursing

- Fertile patients must use effective contraception

- No history of severe congestive heart failure or severe pulmonary disease

- Patients who are status post-revascularization procedures with satisfactory
cardiac function are eligible

- No acute myocardial infarction within the past 6 months

- No significant history of a medical problem or co-morbidity (e.g., severe congestive
heart failure or active ischemic heart disease) that would preclude a major abdominal
operation

- No concurrent second malignancy requiring systemic therapy

- No psychiatric or addictive disorders, or other conditions that would preclude the
patient from meeting the study requirements

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No prior second-line systemic treatment for metastatic colon adenocarcinoma

- Patients who received prior adjuvant therapy for colon adenocarcinoma and/or
prior first-line systemic therapy for metastatic colon adenocarcinoma are
eligible

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall survival (OS)

Safety Issue:

No

Principal Investigator

Alexander Stojadinovic, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Walter Reed Army Medical Center

Authority:

United States: Federal Government

Study ID:

CDR0000681540

NCT ID:

NCT01167725

Start Date:

August 2010

Completion Date:

Related Keywords:

  • Colorectal Cancer
  • mucinous adenocarcinoma of the colon
  • stage III colon cancer
  • stage IV colon cancer
  • Adenocarcinoma
  • Colonic Neoplasms
  • Colorectal Neoplasms

Name

Location

Wake Forest University Comprehensive Cancer CenterWinston-Salem, North Carolina  27157-1096
St. Agnes Hospital Cancer CenterBaltimore, Maryland  21229