Avelumab for MSI-H or POLE Mutated Metastatic Colorectal Cancer

NCT03150706 | Unknown Phase 2

• 1 other identifier: mCRC avelumab
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief 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, Investigator planned a phase II study of avelumab monotherapy in patients with previously treated, metastatic, MMR deficient (MSI-H) or POLE mutated colorectal cancer.

Conditions

Metastatic Colorectal Cancer

Keywords

POLE mutation; mismatch repair deficient; Avelumab

Outcome Measures

Primary Outcomes (1)

• Serum CEA, TSH, T3, free T4, EKG,CT (or MRI) scans of evaluable/measurable lesions by RECIST 1.1.

  During the CRT

  6 weeks(maximum 7 weeks)

Study Arms (1)

Avelumab

EXPERIMENTAL

The mismatch repair deficient or microsatellite instable, or POLE mutated metastatic colorectal cancer patients who were progressed after at least one prior systemic treatment for metastatic setting. After checking the eligibility for the study entry, patients will be entered into the study treatment with avelumab monotherapy.

Drug: Avelumab

Interventions

Avelumab DRUG

Patients will receive 10 mg/kg of avelumab via intravenous infusion every 2 weeks. Response evaluation will be performed every 6 weeks (± 1-week window period). Treatment will be continued until disease progression, unacceptable adverse events or the patient's refusal. Treatment through progression is at the investigator's discretion, and the investigator should ensure that patients do not have any significant, unacceptable, or irreversible toxicity that indicate that continuing treatment will not further benefit the patient. The Investigator should ensure that patients still meet all of the inclusion criteria and none of the exclusion criteria for this study.

Also known as: MSB0010718C

Avelumab

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 4. ≥ 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, D5S345, D17S250)
• Progressed after at least first-line systemic chemotherapy for metastatic setting.
• ≥ 1 measurable lesion(s) by RECIST 1.1.
• Unresectable advanced or metastatic disease.
• Age over 20 years old.
• ECOG 0-1, but final decision by clinical.
• 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 (Cockroft) ≥ 30 ml/min
• Be willing and able to comply with the protocol for the duration of the study.
• Give written informed consent prior to study-specific screening procedures, with the understanding that the patient has the right to withdraw the study at any time, without prejudice.
• Female subjects must either be of non-reproductive potential ( 60 years old and no menses for 1 year without an alternative medical cause, or history of hysterectomy, or history of bilateral tubal ligation, or history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry.
• Women of childbearing potential and men must agree to use highly efficient contraception since signing of the IC form until at least 8 weeks after the last study drug administration.

You may not qualify if:

• Any prior treatment with PD-1 or PD-L1 inhibitor.
• Receipt of the last dose of chemotherapy ≤ 28 days prior to the first dose of study drugs.
• Current or prior use of immunosuppressive medication within 28 days before the first dose of avelumab, with the exceptions for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
• Concurrent or previous history of another primary cancer within 3 years prior to randomisation except for curatively treated cervical cancer in situ, non-melanomatous skin cancer, superficial bladder cancer (pTis and pT1) and curatively treated thyroid cancer of any stage. Concurrent, histologically confirmed, unresected thyroid cancer without distant metastasis could be allowed with the agreement of the chief principal investigator.
• Uncontrolled CNS metastases; permitted if asymptomatic or neurologically stable.
• Prior radiation therapy would be permitted, but non-radiated evaluable lesions should be present at study entry.
• Radiation therapy during study treatment is not permitted, but if the local investigator decides that radiation therapy should be given during study treatments, he should be convinced that there is no evidence of disease progression with agreement of the chief principal investigator.
• Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (\< 6 months prior to enrollment), myocardial infarction (\< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
• Active or prior documented autoimmune disease within the past 2 years; subjects with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.
• Active or prior documented inflammatory bowel disease.
• History of prior immunodeficiency.
• History of allogeneic organ transplantation.
• Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade ≥ 3)
• History of previous clinical diagnosis of active tuberculosis.
• Vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines

Sponsors & Collaborators

• Asan Medical Center: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (1)

Asan Medical Center

Seoul, Songpa, 05505, South Korea

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Turcot syndrome

Interventions

avelumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Tae Won Kim, Professor

  Asan Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 9, 2017
• First Posted: May 12, 2017
• Study Start: May 22, 2017
• Primary Completion: July 31, 2021
• Study Completion: December 31, 2021
• Last Updated: April 3, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)