Pembrolizumab Before Surgery for the Treatment of Mismatch Repair Deficient Locally Advanced Solid Cancers
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|ClinicalTrials.gov Identifier: NCT04082572|
Recruitment Status : Recruiting
First Posted : September 9, 2019
Last Update Posted : October 25, 2019
|Condition or disease||Intervention/treatment||Phase|
|High-Frequency Microsatellite Instability Locally Advanced Malignant Solid Neoplasm Loss of MLH1 Expression Loss of MSH2 Expression Loss of MSH6 Expression Loss of PMS2 Expression Mismatch Repair Protein Deficiency||Biological: Pembrolizumab||Phase 2|
I. To assess the safety of neo-adjuvant pembrolizumab in patients with locally advanced (unresectable primary cancer or resectable primary cancer with a high chance of recurrence) mismatch repair protein deficiency (dMMR) solid organ tumors by Common Terminology Criteria for Adverse Events (CTCAE) assessed toxicity and post-surgical complication assessment by the Clavien-Dindo classification.
II. To assess the rate of complete pathological response for patients who undergo surgical resection following at least 3 doses of neoadjuvant pembrolizumab.
I. To quantify the rate of organ sparing at 1 year for all patients treated with one dose of pembrolizumab (intent to treat) and those patients who receive at least 3 doses of neoadjuvant pembrolizumab and decline to undergo surgical resection and opt to continue receiving pembrolizumab for a total of 1 year.
II. To assess radiographic tumor response to neoadjuvant pembrolizumab. III. To estimate the relapse-free survival and overall survival in all enrolled participants.
IV. To determine the overall rates of pathological response to neoadjuvant pembrolizumab.
V. To assess the rate of complete pathological response (intent to treat) for patients who undergo surgical resection following at least 1 dose of neoadjuvant pembrolizumab.
Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Cycles repeat every 21 days for 1 year in the absence of disease progression or unacceptable toxicity. Patients who do not respond to pembrolizumab and stop the treatment after 2 doses may undergo surgery within 6 months.
After completion of study treatment, patients are followed up at 30 days, every 6 weeks for 1 year, every 12 weeks, and then every 6 months for up to 2 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||35 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Neoadjuvant Pembrolizumab for Patients With Mismatch Repair Deficient Locally Advanced Solid Cancers|
|Actual Study Start Date :||September 17, 2019|
|Estimated Primary Completion Date :||May 3, 2021|
|Estimated Study Completion Date :||May 3, 2021|
Experimental: Treatment (pembrolizumab)
Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for 1 year in the absence of disease progression or unacceptable toxicity. Patients who do not respond to pembrolizumab and stop the treatment after 2 doses may undergo surgery within 6 months.
- Pathological complete response [ Time Frame: At 1 year ]Estimated with 95% confidence interval.
- Rate of organ sparing [ Time Frame: At 1 year ]Estimated with 95% confidence interval.
- Incidence of adverse events [ Time Frame: Up to 2 years ]Safety will be recorded according to Common Terminology Criteria for Adverse Events toxicity and also post-operative complications will be classified according to Clavien-Dindo classification1.
- Overall survival [ Time Frame: From treatment start till death or last follow-up, assessed up to 2 years ]Will be estimated using the method of Kaplan and Meier.
- Relapse-free survival [ Time Frame: Up to 2 years ]Defined as the number of days from the date of response to the date of documented treatment failure, relapses or death from any cause, whichever occurs first. Will be estimated using the method of Kaplan and Meier.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04082572
|Contact: Michael J Overmanfirstname.lastname@example.org|
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Michael J. Overman 713-792-2828|
|Principal Investigator: Michael J. Overman|
|Principal Investigator:||Michael J Overman||M.D. Anderson Cancer Center|