Pembrolizumab vs Chemotherapy in Microsatellite Instability-High or Mismatch Repair Deficient Stage IV Colorectal Cancer
- Conditions
- Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Stage IV Colorectal CarcinomaTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-002024-89-BE
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 300
1. Provide written informed consent for the study.
2. Be male or female who is = 18 years of age on the date of signing informed consent.
3. Have locally confirmed MMR deficient (dMMR) or microsatellite instability high (MSI-H) stage IV colorectal carcinoma
4. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 10 days prior to treatment initiation
5. Have life expectancy of at least 3 months
6. Have measurable disease at baseline based on RECIST 1.1 as determined by the local site Investigator/radiology assessment.
7. Female subjects of childbearing potential must have a negative serum pregnancy test within 72 hours prior to receiving the first dose of study medication.
8. Female subjects of childbearing potential must be willing to use an adequate method of contraception for the course of the study starting with the first dose of study medication through 180 days after the last dose of study medication for the chemotherapy arm and 120 days for pembrolizumab arm, whichever is later.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
9. Male subjects of childbearing potential must agree to use an adequate method of contraception starting with the first dose of study medication through 180 days after the last dose of study medication for the chemotherapy arm and 120 days for pembrolizumab arm, whichever is later.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
10. Demonstrate adequate organ function. All screening laboratory assessments should be performed within 10 days prior to treatment initiation.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 270
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30
1. Has received prior systemic therapy for stage IV CRC. Subjects may have received prior adjuvant chemotherapy for CRC as long as it was completed at least 6 months prior to randomization.
2. Is currently participating and receiving study medication in another study, or has participated in a study of an investigational agent and received study medication, or used an investigational device within 4 weeks of randomization.
3. Has an active autoimmune disease that has required systemic treatment in past 2 years (I.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
4. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to randomization.
5. Has had radiation therapy within 4 weeks prior to randomization of study medication and who has not recovered to baseline from adverse events due to radiation therapy. Subjects who have been given palliative radiotherapy to peripheral sites (e.g., bone metastasis) may enter the study before 4 weeks have elapsed but must have recovered from any acute adverse effects.
6. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they have stable brain metastases [without evidence of progression by imaging as confirmed by magnetic resonance imaging (MRI) if MRI was used at prior imaging, or confirmed by computed tomography (CT) imaging if CT used at prior imaging] at least 4 weeks prior to the first dose of study medication; also, any neurologic symptoms must have returned to baseline], and have not used steroids for brain metastases for at least 28 days prior to trial initiation. This exception does not include carcinomatous meningitis, as subjects with carcinomatous meningitis are excluded regardless of clinical stability.
7. Has had major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to randomization.
8. Has received prior therapy with an immune checkpoint inhibitor (e.g., anti-PD-1, anti-PD-L1, anti-PD-L2 agent, or anti-CTLA-4 agent, etc).
9. Has another malignancy that is progressing or requires active treatment. Exceptions include non-melanomatous skin cancer that has undergone potentially curative therapy and in situ cervical carcinoma.
10. Has received a live vaccine within 30 days of planned start of study medication (see Section 5.5.2).
11. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject’s participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating Investigator.
12. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies), active chronic or acute Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
13. Has known history of, or any evidence of interstitial lung disease or active, non-infectious pneumonitis.
14. Has a known history of active tuberculosis (TB; Bacillus tuberculosis).
15. Has an active infection requiring systemic therapy.
16. Has known psychiatric or substance abuse dis
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: 1) To compare Progression Free Survival (PFS) per RECIST 1.1 by central imaging vendor in subjects with stage IV MSI-H or dMMR CRC treated with first line (1L) pembrolizumab versus SOC chemotherapies.<br>2) To compare Overall Survival (OS) in subjects with stage IV MSI-H ordMMR CRC treated with first line (1L) pembrolizumab versus SOC chemotherapies. ;Secondary Objective: To compare Overall Response Rate (ORR) per RECIST 1.1 by central imaging vendor in subjects with stage IV MSI-H or dMMR CRC treated with first line (1L) pembrolizumab versus SOC chemotherapies.<br>To evaluate the safety and tolerability profiles in subjects with 1L stage IV MSI-H or dMMR CRC treated with pembrolizumab versus SOC chemotherapies.<br>;Primary end point(s): 1) Progression-free Survival (PFS) per RECIST 1.1 by central imaging vendor.<br>2) Overall survival;Timepoint(s) of evaluation of this end point: at interim and final analyses
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Overall response rate;Timepoint(s) of evaluation of this end point: at final analysis