Postoperative Hepatic Arterial Chemotherapy in High-risk Patients as Adjuvant Treatment After Resection of Colorectal Liver Metastases

NCT ID: NCT02494973

Last Updated: 2024-10-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 104 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-26
• Study Completion Date: 2024-03-18

Brief Summary

Currently, no adjuvant study with hepatic arterial infusion in the adjuvant setting is opened. Recently, the results of a phase II study (NCT00268463, NSABP-C-09) assessing the potential benefit of systemic oxaliplatin and capecitabine alternating with HAI of FUDR, after resection of CRLM have been reported.

The primary end point was 2-year survival. Fifty-five of 76 eligible patients were able to initiate protocol-directed therapy and completed median of six cycles (range, one to six). Three postoperative or treatment-related deaths were reported. Overall, 88% of evaluable patients were alive at 2 years. With a median followup of 4.8 years, a total of 30 patients have had disease recurrence, 11 involving the liver. Median disease-free survival was 32.7 months. In conclusion alternating HAI of FUDR and systemic capecitabine and oxaliplatin met the prespecified end point of higher than 85% survival at 2 years and were clinically tolerable.

Conditions

Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Adjuvant systemic chemotherapy with mFOLFOX6

started within 8 weeks after surgery for a maximal duration of 6 months and at least 3 months, every 14 days:

• Oxaliplatin 85 mg/m² in 2 hours IV day (D)1,
• Acide folinique 400 mg/m² in 2 hours IV (concomitantly to oxaliplatin) D1, followed by 5FU bolus 400 mg/m² in 5-10 minutes IV D1 followed by 5FU 2400 mg/m² IV in 46 hours.

Group Type: ACTIVE_COMPARATOR

Oxaliplatin IV

Intervention Type: DRUG

Oxaliplatin 85 mg/m² in 2 hours IV day (D)1,

mFOLFOX6

Intervention Type: DRUG

Acide folinique 400 mg/m² in 2 hours IV (concomitantly to oxaliplatin) D1, followed by 5FU bolus 400 mg/m² in 5-10 minutes IV D1 followed by 5FU 2400 mg/m² IV in 46 hours.

Adjuvant HAI oxaliplatin and systemic LV5FU2

started within 8 weeks after surgery for a maximal duration of 6 months and at least 3 months, and performed every 14 days:

• Oxaliplatin 85 mg/m² in 4-6 hours HAI day (D)1,
• Acide Folinique 400 mg/m² in 2 hours IV (concomitantly to oxaliplatin) D1, followed by 5FU bolus 400 mg/m² in 5-10 minutes IV D1 followed by 5FU 2400 mg / m² IV in 46 hours. In both arms, continuation of targeted therapy (if any) used in the preoperative treatment is allowed.

Group Type: EXPERIMENTAL

Oxaliplatin HAI

Intervention Type: DRUG

Oxaliplatin 85 mg/m² in 2 hours HAI day (D)1,

LV5FU2

Intervention Type: DRUG

Acide Folinique 400 mg/m² in 2 hours IV (concomitantly to oxaliplatin) D1, followed by 5FU bolus 400 mg/m² in 5-10 minutes IV D1 followed by 5FU 2400 mg / m² IV in 46 hours.

Interventions

Oxaliplatin HAI

Oxaliplatin 85 mg/m² in 2 hours HAI day (D)1,

Intervention Type: DRUG

Oxaliplatin IV

Oxaliplatin 85 mg/m² in 2 hours IV day (D)1,

Intervention Type: DRUG

mFOLFOX6

Acide folinique 400 mg/m² in 2 hours IV (concomitantly to oxaliplatin) D1, followed by 5FU bolus 400 mg/m² in 5-10 minutes IV D1 followed by 5FU 2400 mg/m² IV in 46 hours.

Intervention Type: DRUG

LV5FU2

Acide Folinique 400 mg/m² in 2 hours IV (concomitantly to oxaliplatin) D1, followed by 5FU bolus 400 mg/m² in 5-10 minutes IV D1 followed by 5FU 2400 mg / m² IV in 46 hours.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Histologically confirmed metastatic colorectal adenocarcinoma,

2. Curative-intent resection (or ablation) R0 of at least 4 CRLM,

3. Preoperative oxaliplatin- and/or irinotecan-based chemotherapy (successively or concomitantly) +/- non experimental biological therapy, e.g., anti-EGFR or antiangiogenic antibody,

4. Confirmed radiological tumor control before surgery (i.e., objective response or stable disease according to RECIST1.1 criteria),

5. WHO performance status of 0 or 1,

6. Age ≥ 18 years,

7. Adequate hematological function: absolute neutrophil count (ANC) > 2 x 109/L; platelets > 100 x 10^^9/L, hemoglobin (Hb) > 9 g/dL.

8. Adequate liver function: serum bilirubin </= 1.5 x ULN;

9. Aminotransferases levels </= 2.5 ULN (</= 5 ULN if liver metastases in place), and alkaline phosphatase level ≤ 5 ULN

10. Creatinin clearance ≥ 30 ml/min

11. Informed consent signed by the patient or his/her legal representative.

12. Negative pregnancy test in women of childbearing potential within 14 days prior to treatment initiation (premenopausal or less than 12 months of amenorrhea post-menopause, and who have not undergone surgical sterilization). Both men and women (of childbearing potential) who are sexually active must use adequate contraception, during and for at least 6 months post-treatment.

3. Contraindication to fluoropyrimidines or oxaliplatin, as mentioned in the SMPC of investigational medicinal products

4. Known dihydropyrimidine dehydrogenase (DPD) deficiency

5. Disease progression during, or early hepatic relapse (< 6 months) after the end of, oxaliplatin-based adjuvant chemotherapy following primary tumor resection

6. History of hepatic arterial infusion with any treatment (chemotherapy, radioembolisation),

7. Peripheral neuropathy> grade 1,

8. History of cancer within 5 years prior to entry into the trial other than adequately treated basal-cell skin cancer or in situ carcinoma of the cervix

9. Concomitant administration of cimetidine

10. Concomitant medications/comorbidities that may prevent the patient from receiving study treatments,

11. Patient already included in another clinical trial with an experimental molecule,

12. Pregnancy or lactation,

13. Patients deprived of liberty or under guardianship,

14. Patients unable to undergo medical monitoring test for geographical, social or psychological reasons.

15. Patients must not have any uncontrolled concurrent illness including, but not limited to, severe active or uncontrolled infection, symptomatic congestive heart failure, unstable, angina pectoris, cardiac arrhythmia, uncontrolled diabetes mellitus or psychiatric illness/social situations that would limit compliance with study requirements resection is planned (REVERSE strategy authorized)

Exclusion Criteria

1. Extrahepatic metastatic disease (except ≤3 lung nodules (≤10 mm on chest CT scan) deemed amenable to curative-intent resection/ablation),

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute, France

OTHER_GOV

Sponsor Role: collaborator

Gustave Roussy, Cancer Campus, Grand Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Gustave Roussy Cancer Campus Grand Paris

Villejuif, Val De Marne, France

Countries

France

References

Goere D, Pignon JP, Gelli M, Elias D, Benhaim L, Deschamps F, Caramella C, Boige V, Ducreux M, de Baere T, Malka D. Postoperative hepatic arterial chemotherapy in high-risk patients as adjuvant treatment after resection of colorectal liver metastases - a randomized phase II/III trial - PACHA-01 (NCT02494973). BMC Cancer. 2018 Aug 6;18(1):787. doi: 10.1186/s12885-018-4697-7.

Reference Type: DERIVED

PMID: 30081865 (View on PubMed)

Other Identifiers

2014/2187

Identifier Type: OTHER

Identifier Source: secondary_id

2014-005110-32

Identifier Type: -

Identifier Source: org_study_id