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Postoperative Hepatic Arterial Chemotherapy in High-risk Patients as Adjuvant Treatment After Resection of Colorectal Liver Metastases (PACHA-01)

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ClinicalTrials.gov Identifier: NCT02494973
Recruitment Status : Recruiting
First Posted : July 10, 2015
Last Update Posted : July 23, 2018
Sponsor:
Collaborator:
National Cancer Institute, France
Information provided by (Responsible Party):
Gustave Roussy, Cancer Campus, Grand Paris

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.


Condition or disease Intervention/treatment Phase
Colorectal Cancer Drug: Oxaliplatin HAI Drug: Oxaliplatin IV Drug: mFOLFOX6 Drug: LV5FU2 Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 220 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : May 2015
Estimated Primary Completion Date : May 2028
Estimated Study Completion Date : May 2028

Resource links provided by the National Library of Medicine

Drug Information available for: Oxaliplatin

Arm Intervention/treatment
Active Comparator: 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.
Drug: Oxaliplatin IV
Oxaliplatin 85 mg/m² in 2 hours IV day (D)1,

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.

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

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.




Primary Outcome Measures :
  1. 18-month hepatic RFS rate [ Time Frame: Assessed 18 months after inclusion ]
  2. 3-year RFS rate [ Time Frame: Assessed 3 years after inclusion ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02494973


Contacts
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Contact: Diane Goéré, MD 0142115441 ext +33 diane.goere@gustaveroussy.fr
Contact: Jean Pierre Pignon, MD 0142114565 ext +33 jean-pierre.pignon@gustaveroussy.fr

Locations
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France
Gustave Roussy Cancer Campus Grand Paris Recruiting
Villejuif, Val De Marne, France, 94805
Contact: Diane Goéré, MD    0142115441 ext +33    diane.goéré@gustaveroussy.fr   
Contact: Aurélie Abou Lovergne    0142113862 ext +33    aurelie.aboulovergne@gustaveroussy.fr   
Principal Investigator: Diane Goéré, MD         
Sponsors and Collaborators
Gustave Roussy, Cancer Campus, Grand Paris
National Cancer Institute, France

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Gustave Roussy, Cancer Campus, Grand Paris
ClinicalTrials.gov Identifier: NCT02494973     History of Changes
Other Study ID Numbers: 2014-005110-32
2014/2187 ( Other Identifier: CSET number )
First Posted: July 10, 2015    Key Record Dates
Last Update Posted: July 23, 2018
Last Verified: July 2018

Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Oxaliplatin
Levoleucovorin
Antineoplastic Agents
Antidotes
Protective Agents
Physiological Effects of Drugs