Durvalumab for MSI-H or POLE Mutated Metastatic Colorectal Cancer (NCT03435107) | Clinical Trial Compass
CompletedPhase 2
Durvalumab for MSI-H or POLE Mutated Metastatic Colorectal Cancer
South Korea33 participantsStarted 2018-04-12
Plain-language summary
The POLE mutations represent high somatic mutation loads in patients with colorectal cancer, especially in those with MMR proficient or MSS, therefore, tumors harbouring POLE mutations might be susceptible to immune checkpoint blockade.
Based on these reasons, the investigators planned a phase II study of durvalumab monotherapy in patients with previously treated, metastatic, MMR deficient (MSI-H) or POLE mutated colorectal cancer.
Who can participate
Age range20 Years
SexALL
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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
✓. Histologically or cytologically confirmed adenocarcinoma of the colon or the rectum.
✓. Mismatch repair deficient or microsatellite instable (defined below), or POLE mutated tumors A. Mismatch repair deficient: loss of expression by immunohistochemical stains ≥ 1 out of 4 markers (MLH1, MSH2, MSH6, PMS2) B. Microsatellite instable: loss of stability ≥2 out of 5 gene panels (BAT-25, BAT-26, D2S123, D5S346, D17S250)
✓. Refractory to at least one agent of prior treatments(fluoropyrimidines, irinotecan or oxaliplatin) Progressed after at least first-line systemic chemotherapy for metastatic setting (progressed within 6 months after completion of adjuvant chemotherapy is also considered as first-line failure)
✓. ≥ 1 measurable lesion(s) by RECIST 1.1.
✓. Unresectable advanced or metastatic disease.
✓. Age over 20 years old.
✓. ECOG performance status of 0-1 or lower.
✓. Adequate organ functions. A. Bone marrow function: Hemoglobin 9.0≥ g/dL, ANC≥ 1,500/mm3, platelet≥ 100,000/mm3 B. Hepatic functions: bilirubin ≤ 1.5 X ULN, AST/ALT ≤ 2.5 X ULN (≤ 5 X ULN in cases of liver metastasis) C. Renal functions: serum Cr ≤ 1.5 X ULN or calculated CCr (Cockcroft) \> 40 ml/min
Exclusion criteria
✕. Any prior treatment with PD-1 or PD-L1 inhibitor, including durvalumab.
✕. Involvement in the planning and/or conduct of the study.
What they're measuring
1
Objective Response Rates (RECIST 1.1)
Timeframe: First measurement should be at 8weeks from first administration.After first measurement, it should be followed up at every 8weeks until date of progression disease or date of death from any cause, whichever came first, assessed up to 46months..
. Receipt of the last dose of chemotherapy ≤ 28 days prior to the first dose of study drugs.
✕. Mean QT interval corrected for heart rate (QTc) ≥ 470 msec calculated from 3 electrocardiograms (ECGs) using Frediricia's Correction.
✕. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
✕. Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
✕. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician.
✕. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (eg, hormone replacement therapy) is acceptable.