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Metastatic Colorectal Cancer (CRC)Phase 3CRCNCT05378867

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

A Phase 3 study testing TRS003, China-approved Bevacizumab and mFOLFOX6 in people with Metastatic Colorectal Cancer (CRC), run by Zhejiang Teruisi Pharmaceutical Inc..

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Colorectal Cancer (CRC)
What is being tested?
TRS003, China-approved Bevacizumab and mFOLFOX6
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
126 participants
Where
No sites listed yet
Study dates
1 Aug 2022to 1 Jul 2024
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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
  • Platelets ≥ 100,000/uL
  • Serum creatinine < 1.5 × ULN or calculated creatinine clearance (CLcr) > 50 mL/min.
  • Total bilirubin ≤ 1.5 × upper limit of normal (ULN) except for patients with Gilbert's syndrome, who are included if total bilirubin is < 3 × ULN or if direct bilirubin is < 1.5 × ULN.
  • Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 × ULN. For those with hepatic metastases, AST and ALT ≤ 5 × ULN.
  • Albumin ≥ 2.5 g/dL
  • Urinalysis ≤ 1+ protein. Patients that have ≥ 2+ proteinuria must have < 1g of protein on a 24h urine collection.

Who cannot join

  • 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
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  • 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.
  • Any major surgical procedure within 28 days prior to screening or anticipated elective surgery during the study. Any minor surgery such as central vein catheterization within 48 hours prior to the first dose of the study drugs.
  • Hypersensitivity to Chinese hamster ovary cell products or to recombinant human or murine antibodies.
  • Hypersensitivity to oxaliplatin or any other platinum-based drug.
  • Active hepatitis B or hepatitis C virus. Patients with evidence of infection with hepatitis B who have an undetectable viral load are eligible for study entry. Patients with evidence of infection with hepatitis C should have completed curative therapy.
  • History of HIV infection.
  • Pregnant or breast-feeding females
  • Any uncontrolled intercurrent illness or condition that in the judgement of the Investigator may endanger the patient.

Trial locations and contacts

No sites are listed yet.

Hongwei Kang contact

(+86)010-65188368

hongwei.kang@teruisipharm.com

About this study

Official title: 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)

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.

Read the detailed description

This is a randomized, double-blind Phase 3 clinical trial evaluating the interchangeability, by a comparison of PK parameters between non-Switching and the Switching arms following the final switch between TRS003 and Bevacizumab® in patients with metastatic adenocarcinoma of the colon or rectum (please note that Bevacizumab® means China-approved Bevacizumab® in this protocol, unless otherwise specified). 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. There will be 3 switches as detailed in the Treatment section (below) and the Schema. If oxaliplatin-induced neurotoxicity requires discontinuation of oxaliplatin, treatment will continue using leucovorin (LCV) plus 5-fluorouracil (5-FU) in combination with either Bevacizumab® or TRS003 until progressive disease (PD), intolerability, or other cause for stopping treatment.

Being tested
TRS003, China-approved Bevacizumab, mFOLFOX6
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TRS003Biological

    • 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

  • China-approved BevacizumabBiological

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

  • mFOLFOX6Drug

    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.
Study groups in NCT05378867
Study groupRoleWhat they receive
TRS003.ExperimentalLead 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®).
Receives: Biological: TRS003; Biological: China-approved Bevacizumab; Drug: mFOLFOX6
China-approved BevacizumabActive comparatorLead 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
Receives: Biological: China-approved Bevacizumab; Drug: mFOLFOX6

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. AUCtau，Area under the curve over the dosing interval

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

    Measured: Cycle 14 (each cycle is 14 days)

Secondary outcomes (8)

  1. C trough， trough concentration

    Besides AUCtau, the PK parameters to be estimated will include the trough concentration (Ctrough), the maximum concentration (Cmax), and time to reach Cmax (Tmax).

    Measured: Cycle 14 (each cycle is 14 days)

  2. C max，maximum concentration

    Besides AUCtau, the PK parameters to be estimated will include the trough concentration (Ctrough), the maximum concentration (Cmax), and time to reach Cmax (Tmax).

    Measured: Cycle 14 (each cycle is 14 days)

  3. T max，the time to reach Cmax

    Besides AUCtau, the PK parameters to be estimated will include the trough concentration (Ctrough), the maximum concentration (Cmax), and time to reach Cmax (Tmax).

    Measured: Cycle 14 (each cycle is 14 days)

  4. ADA，anti-drug antibody

    anti-drug antibody (ADA) and neutralizing antibody if ADA is positive

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

  5. PFS，Progression-free survival

    Progression-free survival (PFS) is defined as the time from randomization to Investigator-determined PD or death due to any cause in the absence of documented PD.

    Measured: Cycle 14 (each cycle is 14 days)

  6. OS，Overall survival

    Overall survival (OS) is defined as the time from randomization to death due to any cause.

    Measured: Cycle 14 (each cycle is 14 days)

  7. ORR，objective response rate

    ORR in the TRS003 Arm/ORR in the China-approved bevacizumab Arm Confidence interval of ORR in each group will be estimated by the Clopper-Pearson Exact method.

    Measured: Cycle 14 (each cycle is 14 days)

  8. DOR，Duration of response

    Duration of response (DOR) is defined as the time from the date of the first documentation of Investigator-determined response in patients with confirmed objective tumor response (CR or PR) to the first documentation of Investigator determined disease progression (PD) or to death due to any cause in the absence of documented PD.

    Measured: Cycle 14 (each cycle is 14 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 May 2022
  2. Study start1 Aug 2022 (estimated)
  3. Primary completion1 Oct 2023 (estimated)
  4. Study completion1 Jul 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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)
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
126 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05378867
Sponsor's protocol ID
TRS00303002
Acronym
CRC
Status last verified
May 2022
First submitted
21 Apr 2022
Last updated
18 May 2022
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing TRS003, China-approved Bevacizumab and mFOLFOX6 in people with Metastatic Colorectal Cancer (CRC), run by Zhejiang Teruisi Pharmaceutical Inc..

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 18 May 2022. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Hongwei Kang ((+86)010-65188368, hongwei.kang@teruisipharm.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

AUCtau，Area under the curve over the dosing interval (time frame: Cycle 14 (each cycle is 14 days)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05378867.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 May 2022.

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