A Phase II Prospective Trial of mXELOXIRI Reintroduction for mCRC

NCT ID: NCT04508452

Last Updated: 2021-02-02

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 91 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-18
• Study Completion Date: 2023-06-01

Brief Summary

The objective is to evaluate the efficacy and safety of reintroduction of modified XELOXIRI combined with molecular targeted drug in patients with metastatic colorectal cancer (mCRC)

Detailed Description

It is an investigator-initiated, single institution, prospective, single-arm clinical study to evaluate the efficacy and safety of reintroduction of modified XELOXIRI combined with bevacizumab as first-line therapy in patients with unresectable mCRC. Eligible patients will receive 12 cycles of mXELOXIRI with bevacizumab and then MDT will be initiated to determine whether to perform a surgery or receive the maintenance therapy until disease progression (PD). At the time of PD, patients will re-introduce XELOXIRI plus bev at the same doses and schedule previously tolerated, for a maximum of 12 cycles.

Conditions

Unresectable Metastatic Colorectal Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

mXELOXIRI+Bev reintroduction

Patients will receive mXELOXIRI+BEV as first-line therapy (to be repeated every 2 weeks for a maximum of 12 cycles), followed to initiate a MDT to determine whether to perform a surgery or receive maintenance therapy. Maintenance treatment: CAP+BEV. The following CAP+BEV therapy will be repeated in 2-week cycles.

At the time of disease progression, patients will be re-introduced XELOXIRI plus bev at the same doses and schedule previously tolerated, for a maximum of 12 cycles. If no progression occurs during XELOXIRI plus bev, patients will receive maintenance CAP+BEV at the same dose used in the last cycle of the induction treatment.

Group Type: EXPERIMENTAL

Capecitabine-Oxaliplatin-Irinotecan-Bevacizumab Combination

Intervention Type: DRUG

CAP 1,600 mg/sq.m /day (p.o. day1-10) D1-10; Oxaliplatin (OX): 68 mg/sq.m (d.i.v.) D1; Irinotecan (IRI):135 mg/sq.m (d.i.v.) D1; BEV: 5mg/kg (d.i.v.) D1; Administered every 2 weeks.

Interventions

Capecitabine-Oxaliplatin-Irinotecan-Bevacizumab Combination

CAP 1,600 mg/sq.m /day (p.o. day1-10) D1-10; Oxaliplatin (OX): 68 mg/sq.m (d.i.v.) D1; Irinotecan (IRI):135 mg/sq.m (d.i.v.) D1; BEV: 5mg/kg (d.i.v.) D1; Administered every 2 weeks.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Personal written informed consent is obtained after the study has been fully explained

2. Histologically confirmed colon or rectal adenocarcinoma

*Excluding appendix cancer and anal canal cancer

3. Clinically unresectable

4. Borderline resectable liver metastases of colorectal cancer considered to have poor-risk disease not deemed to be suitable for upfront resection if they had one or more of the following features assessed by a local multidisciplinary team: more than four metastases, location and distribution of metastatic disease within the liver unsuitable for resection with clear margins (e.g. involvement of both lobes of liver, invasion of intrahepatic vascular structures), extent of liver involvement precluding resection with adequate post-resection residual liver parenchyma volume for viable liver function in the immediate postoperative period, and inability to retain adequate vascular inflow and outflow to maintain viable liver function.

5. Age at enrollment is >= 18 and <= 75 years

6. Life expectancy of at least 12 weeks.

7. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1

8. .Vital organ functions meet the following criteria within 14 days before enrollment.

If multiple test results are available in that period, the results closest to enrollment will be used. No blood transfusions or hematopoietic factor administration will be permitted within 2 weeks before the date on which measurements are taken.

i. Absolute neutrophil count (ANC): ≥3,000 /cu.mm ii. Platelet count: ≥10.0 × 104/cu.mm iii. Hemoglobin concentration: ≥8.0 g/dL iv. Prothrombin time (PT), activated partial thromboplastin time(APTT): ≤1.5 times upper limit of normal (ULN) v. Total bilirubin: ≤1.5 times ULN (≤3 times ULN for metastases to liver).Aspartate aminotransferase (AST), Alanine aminotransferase (ALT): ≤2.5 times ULN (≤5 times ULN for metastases to liver).vi. Serum creatinine: ≤1.5 times ULN, or creatinine clearance: ≥30 mL/min

Exclusion Criteria

1. Clinically resectable. Major surgical procedure within 28 days prior to study treatment initiation (such as open chest, laparoscopy, thoracoscopic surgery, laparoscopic surgery), unless only colostomy is performed; open biopsy or suturing for major trauma within 14 days of study treatment initiation; or planned major surgical procedure during the study (open chest, laparoscopy) ("major surgical procedures" does not include central venous (CV) port insertion)

2. Previous adjuvant oxaliplatin-containing chemotherapy

3. 5-Fu-containing chemotherapy within 12 months.

4. .Have received any experimental therapy (such as take part in another clinical study) within 4 weeks before treatment;

5. Receiving immunotherapy, chemotherapy, radiotherapy (except palliative radiotherapy), or hormonotherapy, which are not included in study protocol;

6. Untreated brain metastases, spinal cord compression, or primary brain tumor;

7. Pregnant, breastfeeding, positive pregnancy test (women who have menstruated in the last year will be tested), or women who are unwilling to use contraception; men who are unwilling to use contraception during the study

8. Any of the following comorbidities i. Uncontrolled hypertension ii. Uncontrolled diabetes mellitus iii. Uncontrolled diarrhea iv. Peripheral sensory neuropathy (≥Grade 1) v. Active peptic ulcer vi. Unhealed wound (except for suturing associated with implanted port placement) vii. Other clinically significant disease (such as interstitial pneumonia or renal impairment)

9. Subjects with known allergy to the study drugs or to any of its excipients.

10. Any indication of contraindications to chemotherapy;

11. Other active malignancies (synchronous malignancies, and asynchronous malignancies separated by a 5-year disease-free interval) (excluding malignancies that are expected to be completely cured, such as intramucosal carcinoma and carcinoma in situ)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

First Affiliated Hospital of Zhejiang University

OTHER

Sponsor Role: lead

Responsible Party

Feng Ye

Chief physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

Ye Feng, M.D.

Role: CONTACT

yefeng-h1@zju.edu.cn

+8613858191208 ext. 87236858

Jiang Weiqin, M.D.

Role: CONTACT

weiqinjiang@zju.edu.cn

+8615068117618

Facility Contacts

Jiang Weiqin, M.D.

Role: primary

weiqinjiang@zju.edu.cn

+8615068117618

Other Identifiers

TRICAP-2

Identifier Type: -

Identifier Source: org_study_id