Locally Advanced Esophageal and Gastric Cancers (EGC)Phase 2PROCEEDNCT03064490
Pembrolizumab, Radiotherapy, and Chemotherapy in Neoadjuvant Treatment of Malignant Esophago-gastric Diseases (PROCEED)
A Phase 2 study testing Pembrolizumab in people with Locally Advanced Esophageal and Gastric Cancers (EGC), run by Duke University at 1 site in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Locally Advanced Esophageal and Gastric Cancers (EGC)
- What is being tested?
- Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Oct 2017to 22 Nov 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
Read the 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.
- Being tested
- Pembrolizumab
- Medical subject headings
- Stomach Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Also called Keytruda
Neoadjuvant Pembrolizumab ( 3 cycles) administered concurrently with weekly Carboplatin and Paclitaxel and daily radiation therapy; followed by surgical resection and adjuvant Pembrolizumab ( 3 cycles)
| Study group | Role | What they receive |
|---|---|---|
| Single arm interventional study | Other | 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. Receives: Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Pathologic Complete Response (pCR)
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.
Measured: up to 20 weeks
Secondary outcomes (1)
Safety of the Combined Drug Therapy With Radiation Therapy
The number of Grade 3+ non-hematological adverse events of special interest that occurred will be reported.
Measured: Neoadjuvant: from the start of neoadjuvant therapy until surgery, approximately 20 weeks Postoperative: within 30 days after surgery Adjuvant: from the start of adjuvant therapy until 90 days after the last dose of adjuvant therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2017
- Study start17 Oct 2017
- Primary completion24 Feb 2023
- Study completion22 Nov 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Locally Advanced Esophageal and Gastric Cancers (EGC)Studies of the same condition, open and under way.
- More trials run by Duke UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Manisha Palta, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03064490
- Sponsor's protocol ID
- Pro00081010
- Acronym
- PROCEED
- Status last verified
- Apr 2025
- First submitted
- 22 Feb 2017
- Last updated
- 10 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pembrolizumab, Radiotherapy, and Chemotherapy in Neoadjuvant Treatment of Malignant Esophago-gastric Diseases (PROCEED)
- ClinicalTrials.gov ID
- NCT03064490
- Acronym / sponsor ID
- PROCEED / Pro00081010
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Study start
- 17 Oct 2017 (actual)
- Primary completion
- 24 Feb 2023 (actual)
- Study completion
- 22 Nov 2023 (actual)
- First posted
- 27 Feb 2017 (actual)
- Results
- Posted 13 Mar 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single arm interventional study | Other | Drug: PembrolizumabSingle 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (22 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PembrolizumabAlso: KeytrudaNeoadjuvant Pembrolizumab ( 3 cycles) administered concurrently with weekly Carboplatin and Paclitaxel and daily radiation therapy; followed by surgical resection and adjuvant Pembrolizumab ( 3 cycles) | Drug | Single arm interventional study |
Primary outcome
Number of Participants With Pathologic Complete Response (pCR)
Time frame: up to 20 weeks
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.
1 secondary outcome
Safety of the Combined Drug Therapy With Radiation Therapy
Time frame: Neoadjuvant: from the start of neoadjuvant therapy until surgery, approximately 20 weeks Postoperative: within 30 days after surgery Adjuvant: from the start of adjuvant therapy until 90 days after the last dose of adjuvant therapy
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Manisha Palta, MD principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab in people with Locally Advanced Esophageal and Gastric Cancers (EGC), run by Duke University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Pathologic Complete Response (pCR) (time frame: up to 20 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Apr 2025.