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

Primary Purpose

Colorectal Cancer, Metastatic Cancer

Status

Withdrawn

Phase

Phase 2

Locations

France

Study Type

Interventional

Intervention

FOLFIRI regimen

fluorouracil

irinotecan hydrochloride

leucovorin calcium

sunitinib malate

laboratory biomarker analysis

pharmacogenomic studies

pharmacological study

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring stage IV rectal cancer, adenocarcinoma of the rectum, liver metastases, lung metastases

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Hopital Ambroise Pare

Outcomes

Primary Outcome Measures

Response rate at 3 months as assessed by RECIST criteria

Secondary Outcome Measures

Rate of complete response after resection

Rate of R0 resection of metastases

Rate of local failure

Rate of local complications

Metastatic progression-free survival

Local progression-free survival

Disease-free survival

Symptom-free survival

Overall survival

Quality of life, specifically fatigue and global health score (EORTC QLQ-C30)

Time to deterioration of the final score for overall health and fatigue

Tolerance and incidence of side effects as assessed by NCI CTCAE v2

Translational research including pharmacodynamic studies of plasma and rectal tumor biopsies and histological and molecular studies

Full Information

NCT ID

NCT00936832

First Posted

July 8, 2009

Last Updated

August 26, 2022

Sponsor

Federation Francophone de Cancerologie Digestive

1. Study Identification

Unique Protocol Identification Number

NCT00936832

Brief Title

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

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)

Study Type

Interventional

2. Study Status

Record Verification Date

July 2009

Overall Recruitment Status

Withdrawn

Why Stopped

because the sunitinib showed futility in anotehr trial

Study Start Date

April 2009 (undefined)

Primary Completion Date

March 24, 2010 (Actual)

Study Completion Date

March 24, 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Federation Francophone de Cancerologie Digestive

4. Oversight

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Colorectal Cancer, Metastatic Cancer

Keywords

stage IV rectal cancer, adenocarcinoma of the rectum, liver metastases, lung metastases

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

FOLFIRI regimen

Intervention Type

Drug

Intervention Name(s)

fluorouracil

Intervention Type

Drug

Intervention Name(s)

irinotecan hydrochloride

Intervention Type

Drug

Intervention Name(s)

leucovorin calcium

Intervention Type

Drug

Intervention Name(s)

sunitinib malate

Intervention Type

Other

Intervention Name(s)

laboratory biomarker analysis

Intervention Type

Other

Intervention Name(s)

pharmacogenomic studies

Intervention Type

Other

Intervention Name(s)

pharmacological study

Primary Outcome Measure Information:

Title

Response rate at 3 months as assessed by RECIST criteria

Secondary Outcome Measure Information:

Title

Rate of complete response after resection

Title

Rate of R0 resection of metastases

Title

Rate of local failure

Title

Rate of local complications

Title

Metastatic progression-free survival

Title

Local progression-free survival

Title

Disease-free survival

Title

Symptom-free survival

Title

Overall survival

Title

Quality of life, specifically fatigue and global health score (EORTC QLQ-C30)

Title

Time to deterioration of the final score for overall health and fatigue

Title

Tolerance and incidence of side effects as assessed by NCI CTCAE v2

Title

Translational research including pharmacodynamic studies of plasma and rectal tumor biopsies and histological and molecular studies

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

120 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Philippe Rougier, MD

Organizational Affiliation

Hopital Ambroise Pare

Official's Role

Principal Investigator

Facility Information:

Facility Name

Hopital Ambroise Pare

City

Boulogne Billancourt

ZIP/Postal Code

92100

Country

France

12. IPD Sharing Statement

Learn more about this trial

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

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