A Study Assessing the Interchangeability Between TRS003 and Bevacizumab® For CRC

NCT05378867 | Unknown Phase 3 FDA Drug

• 1 other identifier: TRS00303002
• Study Type: interventional
• Target: 126
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a Phase 3, multicenter, randomized and double-blind study assessing the interchangeability between TRS003 and China-approved Bevacizumab® (also called China-approved Avastin) for first-line treatment of patients with metastatic Colorectal Cancer (CRC), approximately 126 patients will be enrolled in this study. Patients who sign the informed consent, meet the eligibility criteria and are confirmed as non-progressors after lead-in treatment period with Bevacizumab® in combination with modified FOLFOX6 chemotherapy for 6 cycles, will be randomized (1:1) to either the non-switching arm and receive Bevacizumab® + modified FOLFOX6 for all subsequent cycles or to the switching arm and receive TRS003 alternating with Bevacizumab® in combination with mFOLFOX6 until disease progression or intolerability.

Conditions

Metastatic Colorectal Cancer (CRC)

Outcome Measures

Primary Outcomes (1)

• AUCtau，Area under the curve over the dosing interval

  The natural log-transformed AUCtau in Cycle 14 will be analyzed.

  Cycle 14 (each cycle is 14 days)

Secondary Outcomes (8)

• C trough， trough concentration

  Cycle 14 (each cycle is 14 days)

• C max，maximum concentration

  Cycle 14 (each cycle is 14 days)

• T max，the time to reach Cmax

  Cycle 14 (each cycle is 14 days)

• ADA，anti-drug antibody

  at Day 1 of every 2 cycles（each cycle is 14 days）

• PFS，Progression-free survival

  Cycle 14 (each cycle is 14 days)

Study Arms (2)

TRS003.

EXPERIMENTAL

Lead in Treatment Period * Will consist of 6 cycles of Bevacizumab® + mFOLFOX6 * Each cycle length is 14 days After completion of the Lead-in Period, patients who have not progressed or experienced intolerable side effects and remain on study will be randomized 1:1 to either the Non-Switch or Switch Arm of the study. Switch Arm * TRS003, 5 mg/kg IV every 14 days with mFOLFOX6 for 1 cycle followed by switch to: * Bevacizumab®, 5 mg/kg IV every 14 days with mFOLFOX6 for 1 cycle followed by switch to: * TRS003, 5 mg/kg IV every 14 days with mFOLFOX6 until end of treatment due to PD, intolerability or other cause for stopping treatment. Intensive PK sampling will be performed after 7 cycles of this TRS003 switch period (to occur during Cycle 14, adequate for washout of preceding Bevacizumab®).

Biological: TRS003; Biological: China-approved Bevacizumab; Drug: mFOLFOX6

China-approved Bevacizumab

ACTIVE COMPARATOR

Lead in Treatment Period * Will consist of 6 cycles of Bevacizumab® + mFOLFOX6 * Each cycle length is 14 days After completion of the Lead-in Period, patients who have not progressed or experienced intolerable side effects and remain on study will be randomized 1:1 to either the Non-Switch or Switch Arm of the study. Non-Switch Arm: * Bevacizumab®, 5 mg/kg administered IV every 14 days * mFOLFOX6 administered as described above every 14 days

Biological: China-approved Bevacizumab; Drug: mFOLFOX6

Interventions

TRS003 BIOLOGICAL

* TRS003, 5 mg/kg IV every 14 days with mFOLFOX6 for 1 cycle followed by switch to: * Bevacizumab®, 5 mg/kg IV every 14 days with mFOLFOX6 for 1 cycle followed by switch to: * TRS003, 5 mg/kg IV every 14 days with mFOLFOX6 until end of treatment due to PD, intolerability or other cause for stopping treatment. Intensive PK sampling will be performed after 7 cycles of this TRS003 switch period

TRS003.

China-approved Bevacizumab BIOLOGICAL

• Bevacizumab®, 5 mg/kg IV every 14 days with mFOLFOX6 for 1 cycle

China-approved Bevacizumab; TRS003.

mFOLFOX6 DRUG

The mFOLFOX6 regimen is: * Oxaliplatin, 85 mg/m2 administered IV over 2 hours * LCV, 400 mg/m2 administered over 2 hours concurrent with oxaliplatin * 5-FU, 400 mg/m2 given as a slow IV push (bolus) over 5 minutes administered immediately after LCV * 5-FU, 2400 mg/m2 administered IV over 46 hours by infusion pump beginning immediately after FU IV bolus.

China-approved Bevacizumab; TRS003.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically documented adenocarcinoma of the colon or rectum
• Must have radiographic documentation of measurable metastatic disease (per RECIST v1.1)
• Patients with resected primary tumors are eligible if documented metastatic disease is present.
• Age ≥ 18 years
• ECOG Performance Status of 0-1
• Patients who received oxaliplatin/fluorouracil-based adjuvant chemotherapy then developed metastatic disease are eligible if \> 12 months since last adjuvant chemotherapy treatment. Consider biopsy to confirm lesions are metastatic colorectal cancer, especially if initial CRC was stage I.
• May have received radiation with radio-sensitizing chemotherapy if completed \> 12 months before enrollment. Patients with rectal cancer who have received locoregional radiation therapy are eligible if they have measurable metastatic disease that is outside the radiation therapy portal.
• Patients with left or right sided primary colon cancers are eligible as are patients with RAS or BRAF mutant tumor (molecular determination is not required).
• Hypertension must be well controlled (\< 150/90) on a stable anti-hypertensive regimen.
• Patients on full-dose anticoagulation or taking anti-platelet agents are eligible if on a stable dose of medication and have no active bleeding or conditions that predispose to bleeding.
• For women of childbearing potential, must consent to use two highly effective methods (i.e., total abstinence, placement of an intrauterine device) of contraception during treatment and for an additional 90 days after the last administration of study drug.
• Men with a partner of childbearing potential, must consent to use two highly effective methods of contraception during treatment and for an additional 90 days after the last administration of study drug.
• Required laboratory values:
• Granulocytes ≥ 1500/uL
• Hemoglobin ≥ 9.0 grams/dL

You may not qualify if:

• Prior systemic or regional treatment for metastatic disease
• Prior exposure to drugs that target VEGF or VEGF receptors (e.g., tyrosine kinase inhibitors, monoclonal antibodies, or soluble receptors).
• Patients whose tumors have microsatellite instability-high or mismatch repair deficiency
• Radiotherapy to greater than 25% of the bone marrow. Standard adjuvant rectal cancer chemoradiation will not exclude the patient.
• Previous or concurrent malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer that the patient has been disease-free for 5 years
• Sensory or peripheral neuropathy of ≥ grade 2 at baseline
• Known central nervous system metastases or carcinomatous meningitis
• Interstitial pneumonia or medically significant interstitial fibrosis of the lung
• Pleural effusion or ascites that causes ≥ grade 2 dyspnea.
• Colon or small bowel disorders with baseline symptoms including 3 watery or soft stools per day (patients without colostomy or ileostomy; patients with stoma may be entered at Investigator's discretion).
• Uncontrolled seizure disorder or active neurological disease
• Current congestive heart failure (NY Heart Association Class II, III, or IV)
• Significant hemorrhagic events within 6 months prior to the study screening including hemoptysis \> 2.5 mL of red blood, gastrointestinal bleeding, hematemesis, central nervous system hemorrhage, severe epistaxis or vaginal bleeding, etc.
• Venous or arterial thrombotic events within 6 months of enrollment, including pulmonary embolism or deep vein thrombosis, transient ischemic attack (TIA), cerebrovascular accident (CVA), unstable angina, or myocardial infarction (MI) requiring surgical or medical intervention. Patients with clinically significant peripheral vascular disease or any other arterial thrombotic event are ineligible.
• Serious or non-healing wound, ulcer, or bone fracture.

Sponsors & Collaborators

• Zhejiang Teruisi Pharmaceutical Inc.: lead

MeSH Terms

Conditions

Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Central Study Contacts

Hongwei Kang

CONTACT

(+86)010-65188368; hongwei.kang@teruisipharm.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This is a double-blind study. Neither the subjects, nor the Investigator, nor the Sponsor knows which drug is being administered to which group. Only the Biostatistician who generated the actual randomization scheme with IWRS and the Pharmacist or nurse at the study center who prepares the study drugs and dose for the subjects will be unblinded. All other study related individuals including ancillary clinical staff, biological laboratory staff, clinical research associates, medical monitors, and scientific operation and management team at the study center will remain blinded to the treatment assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A Phase 3, Multicenter, Randomized and Double-blind Study Assessing the Interchangeability between TRS003 and China-approved Bevacizumab® (also called China-approved Avastin) For First-Line Treatment of Patients with Metastatic Colorectal Cancer (CRC)

Study Record Dates

• First Submitted: April 21, 2022
• First Posted: May 18, 2022
• Study Start: August 1, 2022
• Primary Completion: October 1, 2023
• Study Completion: July 1, 2024
• Last Updated: May 18, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share