A Phase II Study of Pembrolizumab in Previously Treated Subjects with Mismatched Repair Deficient or Microsatellite Instability-High Colorectal Carcinoma
- Conditions
- Colorectal CarcinomaTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-001852-32-DE
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 120
Subjects must: be male or female subjects who are = 18 years of age on
the day of signing the informed consent. Locally confirmed MMR
deficient or MSI-h CRC. Have a histologically proven locally advanced
unresectable or metastatic (Stage IV) CRC. Have been previously treated with standard therapies, which must include, for Cohort A, fluoropyrimidine, oxaliplatin and irinotecan and for Cohort B, at least 1 line of systemic standard of care therapy (fluoropyrimidine + oxaliplatin or fluoropyrimidine + irinotecan +/- anti-VEGF/EGFR monoclonal antibody). Subjects who have withdrawn from therapy standard treatment due to unacceptable toxicity warranting discontinuation of that treatment and precluding retreatment with the same agent before progression of disease will also be eligible. Regimens given with adjuvant intent will be counted as treatment for metastatic disease if the patient's disease had progressed within 6 month following treatment. Have an ECOG performance status of 0 or 1. Have a life expectancy of greater than 3 months. Have at least one measureable lesion by RECIST 1.1 as determined by central review for response assessment. Provide an archival or newly obtained tumor tissue sample (Cohort B). Subjects failing screening criteria in Cohort A may be rescreened for Cohort B only after consultation with the SPONSOR.
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 110
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10
Subjects will be excluded if he/she: is currently participating in another
study and receiving trial treatment, has participated in a study of an
investigational agent and received trial treatment within 4 weeks of the
first dose of treatment in this study, or used an investigational device
within 4 weeks of the first dose of treatment in this study. 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. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to
the first dose of trial treatment.
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 [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] for at least four weeks prior to the first dose of trial treatment; also, any
neurologic symptoms must have returned to baseline], have no evidence of new or enlarging brain metastases, and have not used steroids for brain metastases for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis, as subjects with carcinomatous meningitis are excluded regardless of clinical stability. Has had prior monoclonal antibody (mAb), chemotherapy, targeted small
molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1 or at baseline) from adverse events due to a previously administered agent. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. Has received a live vaccine within 30 days of planned start of study therapy. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected). Has known history of, or any evidence of interstitial lung disease or active, non-infectious pneumonitis. Has an active infection requiring systemic therapy.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method