Efficacy of Sacituzumab Govitecan Versus Standard of Care in Metastatic Refractory Colorectal Cancer: A Phase II/III Randomized Multicenter Trial
- Trial ID
- 2023-509771-17-00
- Protocol
- NCT_GI_BCK_01
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this randomized, open-label, multicenter phase II/III trial is to evaluate the **efficacy** of the antibody-drug conjugate Sacituzumab Govitecan, a TROP2 targeted approach, in patients with **Metastatic Colorectal Cancer (mCRC)**. The trial aims to determine the efficacy of Sacituzumab Govitecan by assessing progression-free survival in the initial single-arm phase (PART I). If high clinical efficacy is observed, the subsequent randomized phase (PART II) will compare the superiority of Sacituzumab Govitecan to the standard of care, which is determined by the physician's choice. This evaluation is clinically relevant as it may offer a new therapeutic option for patients with mCRC, potentially improving outcomes in a population with limited treatment options.
Secondary objectives include:
- Assessing overall survival (OS)
- Evaluating the overall response rate (ORR)
- Determining the disease control rate (DCR)
- Measuring the duration of response (DOR)
Participants
The clinical trial focuses on individuals diagnosed with **Metastatic Colorectal cancer (mCRC)**, specifically targeting those with a diagnosis of UICC Stage IV mCRC who are not eligible for local therapy. The study population includes both men and women aged 18 years and older, with no upper age limit, and an ECOG performance status of 0 to 2. Participants must have previously failed or been intolerant to standard therapies, including fluoropyrimidine, oxaliplatin, and irinotecan, and must not have received irinotecan treatment within the last six months unless they were responsive to prior irinotecan induction therapy. The trial does not involve a vulnerable population. Participants are required to have at least one measurable lesion according to RECIST 1.1 criteria, suitable for repeated assessment. The sponsor has not provided information regarding the total number of participants in the trial.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy of **sacituzumab govitecan** in patients with metastatic colorectal cancer (mCRC). This trial is structured as a randomized, open-label, multicenter phase II/III study. The trial is divided into two parts: Part I is a single-arm study assessing efficacy through progression-free survival, and Part II is a randomized comparison of sacituzumab govitecan against the standard of care, determined by the physician's choice. The trial is expected to commence recruitment in May 2024 and conclude by August 2028, with a maximum treatment period of 24 months for participants.
Participants will undergo a series of study visits, beginning with a screening visit to confirm eligibility based on criteria such as a diagnosis of UICC Stage IV mCRC, age of 18 years or older, and an ECOG performance status of 2 or less. The screening will include assessments like computed tomography or magnetic resonance imaging to identify measurable lesions. Following successful screening, participants will enter the treatment phase, with regular follow-up visits to monitor disease progression and treatment response. The primary endpoint is progression-free survival, while secondary endpoints include overall survival, overall response rate, disease control rate, and duration of response.
The expected length of participant involvement is up to 24 months, contingent on disease progression and treatment tolerance. Conditions that may lead to early termination from the study include significant adverse events, withdrawal of consent, or any clinical decision by the investigator deeming it in the participant's best interest to discontinue. The end-of-study visit will occur upon completion of the treatment period or earlier if the participant exits the study prematurely. This visit will include final assessments to evaluate the overall outcomes of the treatment regimen.
Treatment
The clinical trial involves the administration of several treatments, including **Regorafenib**, which is provided in the form of a film-coated tablet. The active substance, regorafenib, is a chemical compound administered orally. The maximum daily dose is 160 mg, with a total dose not exceeding 160 mg per day. The treatment period is set for a maximum of 24 weeks. Compliance with the dosing schedule is monitored to ensure adherence to the protocol.
Another treatment used in the trial is a combination of **Trifluridine** and **Tipiracil**, classified under the ATC code L01BC59. This combination is also administered orally, with a pharmaceutical form designated as PHF00082MIG. The maximum daily dose is 70 mg/m², with a total dose not exceeding 70 mg/m² per day. The treatment duration is capped at 24 weeks. Participant compliance is closely monitored to maintain the integrity of the study.
**Sacituzumab Govitecan** is utilized as the experimental medication in this trial. It is a humanized monoclonal antibody administered via infusion, with a pharmaceutical form identified as PHF00230MIG. The maximum daily dose is 10 mg/kg, with a total dose not exceeding 10 mg/kg per day. The treatment period is limited to 24 weeks. The administration schedule is strictly followed, and participant adherence is monitored throughout the study.
**Bevacizumab** is included as a comparator treatment in the trial. It is a humanized monoclonal antibody administered through infusion, with a pharmaceutical form also designated as PHF00230MIG. The maximum daily dose is 5 mg/kg, with a total dose not exceeding 5 mg/kg per day. The treatment duration is set for a maximum of 24 weeks. Compliance with the dosing regimen is ensured through regular monitoring.
Efficacy
The efficacy of the clinical trial will be assessed primarily through **Progression Free Survival (PFS)**, defined as the time from the first day of treatment (C1D1) in part 1 or randomization in part 2 until disease progression or death from any cause, whichever occurs first. Secondary endpoints include **Overall Survival (OS)**, measured from C1D1 or randomization until death or the end of the study, **Overall Response Rate (ORR)**, which includes Partial Response (PR) or Complete Response (CR), **Disease Control Rate (DCR)**, encompassing CR, PR, or Stable Disease (SD), and **Duration of Response (DOR)**, calculated from the achievement of PR/CR until disease recurrence, progression, or death from any cause.
The trial is structured in two parts: the first part is a single-arm study assessing efficacy through PFS, and the second part is a randomized comparison of Sacituzumab Govitecan against the standard of care. Efficacy assessments will be conducted using validated criteria, such as RECIST 1.1, to evaluate measurable lesions through computed tomography or magnetic resonance imaging. These assessments will be performed at specified intervals to ensure accurate and consistent data collection throughout the trial duration.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Diagnosis of UICC Stage IV mCRC, not eligible for local therapy
- Women or men aged ≥ 18 years, no upper age limit
- ECOG performance status ≤2
- Patients must have failed standard therapy or were intolerable towards standard therapy which must include fluoropyrimidine, oxaliplatin and irinotecan. (Targeted therapies (in combination with chemotherapy) including antiangiogenic monoclonal antibody/fusion protein/small molecule (e.g. bevacizumab, aflibercept, ramucirumab) and anti-EGFR antibody (e.g. Cetuximab, Panitumumab) are allowed as previous therapies.)
- No Irinotecan treatment within the last 6 months. Patients that received Irinotecan treatment more than 6 months prior to inclusion, must have been responsive to Irinotecan induction therapy (i.e., patients previously exposed to induction chemotherapy containing irinotecan must have presented CR or PR or else SD at least 3 months or at initial response assessment).
- At least one measurable lesion according to RECIST 1.1 that can be accurately assessed at screening by computed tomography or magnetic resonance imaging and is suitable for repeated assessment or available CT scan of thorax and abdomen not older than 30 days before start of treatment (day 1 of cycle 1).
Exclusion Criteria
- Patient with a known hypersensitivity to any of the excipients of sacituzumab govitecan
- Participation in other clinical trials involving an investigational drug(s) (Phases 1-4) or observation period of competing trials, respectively within 4 weeks prior to study entry. Patients participating in observational studies are eligible.
- Taking medications that may interfere with SN-38 metabolism.
- Have had a prior anticancer biologic agent within 2 weeks prior to enrollment or have had prior chemotherapy, targeted therapy, or radiation therapy within 2 weeks prior to enrollment AND have not recovered (ie, ≥ Grade 2 is considered not recovered) from AEs at the time of study entry.
- Have not recovered (ie, ≥ Grade 2 is considered not recovered) from AEs due to a previously administered agent.
- Have an active second malignancy.
- History of significant cardiovascular disease ( NYHA ≥ III)
- Clinical signs of active severe infection with or without requiring antibiotics.
- Inadequate bone marrow, renal, and hepatic function defined by laboratory tests within 14 days prior to study treatment (growth factor support is not allowed within 14 days prior to baseline labs
- Known microsatellite instable (MSI-H) / MMR-protein deficient (dMMR) colorectal cancer.
- Pregnancy and lactation
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Germany | Not Recruiting | 01 May 2024 | 80 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
REGORAFENIB | Comparator | — | ORAL | 160 | 24 | SUB73090 |
TRIFLURIDINE, COMBINATIONS | Comparator | PHF00082MIG | ORAL | 70 | 24 | SCP12480833 |
SACITUZUMAB GOVITECAN | Test | PHF00230MIG | INFUSION | 10 | 24 | SCP53436014 |
BEVACIZUMAB | Comparator | PHF00230MIG | INFUSION | 5 | 24 | SCP29096188 |