- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03064490
Pembrolizumab, Radiotherapy, and Chemotherapy in Neoadjuvant Treatment of Malignant Esophago-gastric Diseases (PROCEED) (PROCEED)
February 13, 2024 updated by: Duke University
This is a single-institution, prospective phase II trial with an initial safety run-in to evaluate the efficacy and safety of neoadjuvant pembrolizumab combined with chemoradiotherapy and adjuvant pembrolizumab in patients with locally advanced esophageal and gastric cancers (EGC).
Chemoradiation therapy (45Gy in 25 fractions with concurrent, weekly carboplatin [AUC 2] and paclitaxel [50mg/m2 of BSA]) with three cycles of pembrolizumab will be administered as neoadjuvant therapy.
These patients will also receive three cycles of adjuvant pembrolizumab after surgical resection
Study Overview
Status
Completed
Intervention / Treatment
Detailed Description
Enrolled patients will receive three doses of neoadjuvant pembrolizumab (200 mg administered as an intravenous infusion over 30 minutes every 3 weeks).
The first dose of pembrolizumab will be administered approximately 14 days prior to initiating radiotherapy.
The second dose will be administered three weeks later (week 1 of chemoradiation).
The third dose will be administered 3 weeks later (week 4 of chemoradiotherapy).
Pembrolizumab will be given every 3 weeks and may be given at the same time as systemic therapy.
All patients will receive radiation treatment (45Gy in 25 fractions at 1.8 Gy/fraction) using image-guided radiation therapy with concurrent, weekly carboplatin (AUC 2) and paclitaxel (50mg/m2 of BSA).
Restaging will be performed per standard of care approximately 4-8 weeks after completing chemoradiotherapy.
Resection will be performed approximately 6-12 weeks after completing chemoradiotherapy per standard of care.
Postoperatively, three additional cycles of pembrolizumab (200 mg every 3 weeks) will be administered as adjuvant therapy.
Study Type
Interventional
Enrollment (Actual)
35
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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North Carolina
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Durham, North Carolina, United States, 27710
- Duke Cancer Center
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Be willing and able to provide written informed consent for the trial.
- Be 18 years of age or older on day of signing informed consent.
- Has a pathologic diagnosis of invasive esophageal, gastroesophageal or gastric adenocarcinoma.
- Staging CT CAP or PET/CT shows no evidence of metastatic disease.
- Have a performance status of 0-2 on the ECOG Performance Scale.
- Plan for neoadjuvant chemoradiation.
- Demonstrate adequate organ function as defined in the study protocol, all screening labs should be performed within 14 days of treatment initiation.
- Female subject of childbearing potential should have a negative serum pregnancy within 48 hours prior to receiving the first dose of study medication.
- Female and male subjects of childbearing potential must be willing to use an adequate method of contraception as outlined in the Duke Contraception Policy.
Exclusion Criteria:
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of 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 a known history of active TB (Bacillus Tuberculosis)
- Hypersensitivity to pembrolizumab or any of its excipients.
- Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
- Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy for the current diagnosis of EGC.
- 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. (all patients with prior radiotherapy must be reviewed by the PI to determine if patient is eligible).
- Has known metastatic disease. Staging CT C/A/P or PET/CT will be mandatory no more than 45 days prior to enrollment to evaluate for the presence of metastatic disease.
- Has unresectable disease or is medically inoperable.
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with chronic use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Has known history of, or any evidence of active, non-infectious pneumonitis.
- Has an active infection requiring systemic 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 known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
- 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 received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
- Has a diagnosis of scleroderma.
- Has a known history of allogenic stem cell transplant
- Has received a solid organ transplant
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: Single arm interventional study
Single arm, non randomized, open label study.
Subjects will receive three doses of neoadjuvant pembrolizumab (200 mg administered as an intravenous infusion over 30 minutes every 3 weeks).
Pembrolizumab will be administered with weekly standard of care Carboplatin/Paclitaxel concurrent chemo-radiation therapy in the neo-adjuvant setting.
Postoperatively, three additional cycles of pembrolizumab (200 mg every 3 weeks) will be administered as adjuvant therapy.
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Neoadjuvant Pembrolizumab ( 3 cycles) administered concurrently with weekly Carboplatin and Paclitaxel and daily radiation therapy; followed by surgical resection and adjuvant Pembrolizumab ( 3 cycles)
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Pathologic Complete Response (pCR)
Time Frame: up to 20 weeks
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A two-stage design will be used to test the null hypothesis that the true pCR rate is ≤ 0.30 against the alternative hypothesis that the true pCR rate is ≥ 0.50.
This design will allow the trial to stop early to accept the null hypothesis.
If there are no more than 4 responders (27%) in the first 15 evaluable patients, the trial will stop to accept the null.
Otherwise, an additional 15 evaluable patients will be accrued.
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up to 20 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety of the Combined Drug Therapy With Radiation Therapy.
Time Frame: up to 51 weeks
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Toxicity by type and grade will be tabulated.
Toxicity rates of interest will be calculated with their 80% confidence intervals.
After the first 5 subjects have been accrued, an analysis will be performed to assess acute treatment-related toxicities.
If more than 1, grade 3 or greater toxicities definitely related to concurrent pembrolizumab and radiotherapy are observed, then an additional five patients will be added to this treatment arm.If no issues concerning for safety are observed within 30 days of the last dose of neoadjuvant pembrolizumab (cycle 3) for the fifth patient, then the study will continue to accrue.
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up to 51 weeks
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Manisha Palta, MD, Duke University
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
October 17, 2017
Primary Completion (Actual)
February 24, 2023
Study Completion (Actual)
November 22, 2023
Study Registration Dates
First Submitted
February 22, 2017
First Submitted That Met QC Criteria
February 24, 2017
First Posted (Actual)
February 27, 2017
Study Record Updates
Last Update Posted (Actual)
March 13, 2024
Last Update Submitted That Met QC Criteria
February 13, 2024
Last Verified
February 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- Pro00081010
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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