Sunitinib Malate and Combination Chemotherapy as Front-Line Therapy in Treating Patients With Metastatic Rectal Cancer That Cannot Be Removed by Surgery

This study has been withdrawn prior to enrollment.
(because the sunitinib showed futility in anotehr trial)
Sponsor:
Information provided by (Responsible Party):
Federation Francophone de Cancerologie Digestive
ClinicalTrials.gov Identifier:
NCT00936832
First received: July 8, 2009
Last updated: March 3, 2014
Last verified: July 2009
  Purpose

RATIONALE: Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as irinotecan hydrochloride, leucovorin calcium, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) together with sunitinib malate may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving sunitinib malate together with combination chemotherapy works as front-line therapy in treating patients with metastatic rectal cancer that cannot be removed by surgery.


Condition Intervention Phase
Colorectal Cancer
Metastatic Cancer
Drug: FOLFIRI regimen
Drug: fluorouracil
Drug: irinotecan hydrochloride
Drug: leucovorin calcium
Drug: sunitinib malate
Other: laboratory biomarker analysis
Other: pharmacogenomic studies
Other: pharmacological study
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: Front-line Combination Therapy of Sunitinib Malate Plus Chemotherapy With Leucovorin/5-Fluorouracil and Irinotecan (FOLFIRI) for Rectal Cancer Patients With Synchronous Non-Resectable Metastases: A Phase II Non Controlled Study. (SUREMETS)

Resource links provided by NLM:


Further study details as provided by Federation Francophone de Cancerologie Digestive:

Primary Outcome Measures:
  • Response rate at 3 months as assessed by RECIST criteria [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Rate of complete response after resection [ Designated as safety issue: No ]
  • Rate of R0 resection of metastases [ Designated as safety issue: No ]
  • Rate of local failure [ Designated as safety issue: No ]
  • Rate of local complications [ Designated as safety issue: No ]
  • Metastatic progression-free survival [ Designated as safety issue: No ]
  • Local progression-free survival [ Designated as safety issue: No ]
  • Disease-free survival [ Designated as safety issue: No ]
  • Symptom-free survival [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Quality of life, specifically fatigue and global health score (EORTC QLQ-C30) [ Designated as safety issue: No ]
  • Time to deterioration of the final score for overall health and fatigue [ Designated as safety issue: No ]
  • Tolerance and incidence of side effects as assessed by NCI CTCAE v2 [ Designated as safety issue: Yes ]
  • Translational research including pharmacodynamic studies of plasma and rectal tumor biopsies and histological and molecular studies [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: April 2009
Detailed Description:

OBJECTIVES:

Primary

  • Evaluation of the efficacy of front-line treatment with sunitinib malate and FOLFIRI chemotherapy at 3 months in patients with rectal cancer and synchronous metastases deemed unresectable in a multidisciplinary consultation.

Secondary

  • Evaluate the rate of resection of secondary metastases and rectal cancer, rate of R0 resection of metastases and rectal cancer, and the rate of complete response after resection.
  • Evaluate the rate of local failure (progression of rectal cancer).
  • Evaluate the rate of local complications.
  • Evaluate disease-free survival.
  • Evaluate progression-free survival, metastatic progression-free survival, and local progression-free survival.
  • Evaluate symptom-free survival.
  • Evaluate overall survival.
  • Evaluate quality of life, specifically fatigue and global health score (EORTC QLQ-C30).
  • Evaluate the tolerance to treatment.
  • Conduct translational research, in particular, pharmacokinetic studies of plasma and rectal tumor biopsies, and histological and molecular studies.

OUTLINE: Patients receive simplified FOLFIRI chemotherapy comprising irinotecan hydrochloride IV over 90 minutes, leucovorin calcium IV over 2 hours, and fluorouracil IV over 46 hours on days 1, 15, and 29. Patients also receive oral sunitinib malate once daily on days 1-28. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.

Patients may undergo surgical resection and/or local radiotherapy if the tumor regresses. After resection or radiotherapy, patients may undergo up to 4 more courses of study treatment.

Biopsies of the tumor and healthy mucosa are collected for translational research at baseline. Blood samples are collected for pharmacodynamic and pharmacogenetic studies at baseline and at week 6. Patients also complete a quality-of-life questionnaire (EORTC QLQ-C30) at baseline and periodically thereafter.

After completion of study therapy, patients are followed up every 12 weeks.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed adenocarcinoma of the rectum

    • Lower pole of the tumor < 12 cm from the anal margin
  • Synchronous metastases of the liver and/or lung

    • Unresectable or resectability uncertain according to the decision of a local multidisciplinary consultation
  • Lesions measurable in 1 dimension by RECIST criteria (metastases and primary rectal cancer)
  • No rectal obstruction requiring surgery or the emergency fitting of a prosthesis
  • No CNS metastases

PATIENT CHARACTERISTICS:

  • WHO performance status 0-2
  • ANC ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Creatinine clearance ≥ 60 mL/min
  • Hemoglobin ≥ 10 g/dL (transfusions allowed)
  • FEV ≥ 50%
  • QT interval ≤ 450 ms (in men) or ≤ 470 ms (in women)
  • Total bilirubin ≤ 1.5 times upper limit of normal
  • Serum albumin ≥ 25 g/L
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No history of another cancer except for nonmelanoma skin cancer or curatively treated carcinoma in situ of the cervix

    • History of other cancers allowed provided the patient has been disease-free > 3 years
  • None of the following:

    • Congestive heart failure or coronary heart disease
    • Myocardial infarction within the past year
    • Uncontrolled hypertension (systolic BP > 160 mm Hg or diastolic BP > 100 mm Hg) despite optimal medical management
  • No active severe rectal bleeding
  • No liver failure
  • No known Gilbert syndrome
  • No severe uncontrolled infection
  • No chronic diarrhea, malabsorption syndrome, or intestinal obstruction/subocclusion
  • No severe uncontrolled pain (visual analogue scale 5/10) with morphine treatment
  • No other medical, psychological, or social condition that, in the investigator's opinion, could affect the patient's compliance with study treatment
  • No hypersensitivity to any component of study treatment

PRIOR CONCURRENT THERAPY:

  • See Patient Characteristics
  • No prior radiotherapy to the pelvis
  • More than 4 weeks since prior experimental therapy
  • More than 7 days since prior CYP3A4 inhibitor before the administration of sunitinib malate
  • More than 12 days since prior CYP3A4 inducer
  • No concurrent participation in another clinical study
  • No other concurrent anticancer therapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00936832

Locations
France
Hopital Ambroise Pare
Boulogne Billancourt, France, 92100
Sponsors and Collaborators
Federation Francophone de Cancerologie Digestive
Investigators
Principal Investigator: Philippe Rougier, MD Hopital Ambroise Pare
  More Information

Additional Information:
No publications provided

Responsible Party: Federation Francophone de Cancerologie Digestive
ClinicalTrials.gov Identifier: NCT00936832     History of Changes
Other Study ID Numbers: CDR0000637832, FFCD-0801, EUDRACT-2008-005959-19, EU-20918
Study First Received: July 8, 2009
Last Updated: March 3, 2014
Health Authority: Unspecified

Keywords provided by Federation Francophone de Cancerologie Digestive:
stage IV rectal cancer
adenocarcinoma of the rectum
liver metastases
lung metastases

Additional relevant MeSH terms:
Rectal Neoplasms
Colorectal Neoplasms
Neoplasm Metastasis
Neoplasms
Neoplasms, Second Primary
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Colonic Diseases
Neoplastic Processes
Pathologic Processes
Fluorouracil
Irinotecan
Sunitinib
Camptothecin
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on August 28, 2014