A Phase II Prospective Trial of mXELOXIRI Reintroduction for mCRC

A Phase II Prospective Trial of mXELOXIRI Reintroduction for the Unresectable Metastatic Colorectal Cancer

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)

Study Overview

• Status: Recruiting
• Conditions: Unresectable Metastatic Colorectal Carcinoma
• Intervention / Treatment: Drug: Capecitabine-Oxaliplatin-Irinotecan-Bevacizumab Combination

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.

• Study Type: Interventional
• Enrollment (Anticipated): 91
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ye Feng, M.D.; Phone Number: 87236858 +8613858191208; Email: yefeng-h1@zju.edu.cn
• Study Contact Backup: Name: Jiang Weiqin, M.D.; Phone Number: +8615068117618; Email: weiqinjiang@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Recruiting
      • The first Affiliated Hospital, Zhejiang University School of Medicine
      • Contact: Jiang Weiqin, M.D.; Phone Number: +8615068117618; Email: weiqinjiang@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reintroduction Rate	The rate of patients who receive reintroduction therapy after the first progression.	Up to 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
R0 rate	resection rate	Up to 18 months
PFS	the time from randomization to the first documentation of objective disease progression or death due to any cause, whichever occurs first.	Up to 18 months
OS	the time from randomization to the date of death due to any cause.	Up to 18 months
PFS1	the time from randomization to the first documentation of objective disease progression or death due to any cause before second-line therapy, whichever occurs first.	Up to 18 months
ORR1	percentage of patients, relative to the total of enrolled subjects, achieving a complete (CR) or partial (PR) response, according to RECIST 1.1 criteria, during the first-line induction and the maintenance phases of treatment.	Every 8 weeks, up to 18 months after last patient last visit
PFS2	from the beginning of the second-line treatment to the documentation of objective disease progression or death due to any cause, whichever occurs first	up to 18 months after last patient last visit
ORR2	percentage of patients, relative to the total of enrolled subjects, achieving a complete (CR) or partial (PR) response, according to RECIST 1.1 criteria, during the second-line induction and the maintenance phases of treatment.	Every 8 weeks, up to 18 months after last patient last visit

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): May 18, 2020
• Primary Completion (Anticipated): June 1, 2022
• Study Completion (Anticipated): June 1, 2023

Study Registration Dates

• First Submitted: August 9, 2020
• First Submitted That Met QC Criteria: August 9, 2020
• First Posted (Actual): August 11, 2020

Study Record Updates

• Last Update Posted (Actual): February 2, 2021
• Last Update Submitted That Met QC Criteria: January 31, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Topoisomerase I Inhibitors; Capecitabine; Oxaliplatin; Bevacizumab; Irinotecan
• Other Study ID Numbers: TRICAP-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes