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

Colorectal Cancer Clinical Trial

— PACHA-01  

Official title:

Postoperative Hepatic Arterial Chemotherapy in High-risk Patients as Adjuvant Treatment After Resection of Colorectal Liver Metastases - A Randomized Phase II/III Trial

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT02494973
• Other study ID #: 2014-005110-32
• Secondary ID: 2014/2187
• Status: Suspended
• Phase: Phase 2/Phase 3
• Start date: May 26, 2015
• Est. completion date: May 2028

Study information

• Verified date: August 2023
• Source: Gustave Roussy, Cancer Campus, Grand Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 104
• Est. completion date: May 2028
• Est. primary completion date: May 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Exclusion Criteria:

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

2. Symptomatic primary tumor requiring urgent surgery, asymptomatic primary colorectal tumor is not a non-inclusion criteria if its

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)

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Drug:
• Oxaliplatin HAI
Oxaliplatin 85 mg/m² in 2 hours HAI day (D)1,
• Oxaliplatin IV
Oxaliplatin 85 mg/m² in 2 hours IV day (D)1,
• 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.
• 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.

Locations

Country	Name	City	State
France	Gustave Roussy Cancer Campus Grand Paris	Villejuif	Val De Marne

Sponsors (2)

Lead Sponsor	Collaborator
Gustave Roussy, Cancer Campus, Grand Paris	National Cancer Institute, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	18-month hepatic RFS rate		Assessed 18 months after inclusion
Primary	3-year RFS rate		Assessed 3 years after inclusion