Rectal NeoplasmsPhase 1NCT04357587
Safety and Feasibility of PD-1 Blockade in the Treatment of dMMR or MSI-H Rectal Cancer
A Phase 1 study testing Pembrolizumab, External beam radiation and Capecitabine in people with Rectal Neoplasms, run by Case Comprehensive Cancer Center at 1 site in United States.
Trial summary
Colorectal cancer is the third most common cancer worldwide and the second leading cause of cancer mortality in the United States. The current standard of care (SOC) for locally advanced rectal cancer includes neoadjuvant chemotherapy and radiation followed by surgery. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rectal Neoplasms
- What is being tested?
- Pembrolizumab, External beam radiation and Capecitabine
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Aug 2020to 25 Sep 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Must have confirmed rectal adenocarcinoma Defined as, MRI based clinical stage II (T3-4, N0), stage III (T1-4, N+), or oligometastatic locally advanced stage IV that are candidates for curative surgery
- Tumor location at and/or below the peritoneal reflection on MRI.
- Review and discussion at multidisciplinary tumor board with consensus recommendation for neoadjuvant chemoradiation followed by curative-intent surgery. Documented in EPIC tumor board.
- MMR-deficiency confirmed on immunohistochemistry or MSI status confirmed by PCR.
- ECOG Performance status 0-1
- Life expectancy of ≥ 6 months, in the opinion of and as documented by the treating physician.
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- Must have normal organ and marrow function as defined below:
- Hemoglobin ≥ 8.0 g/dL
- Leukocytes ≥ 3,000/k/uL
- Absolute neutrophil count ≥ 1,500/k/uL
- Platelet count ≥ 100,000/k/uL
- Total bilirubin ≤ 1.3 x institutional upper limit of normal (ULN)
- AST (SGOT) ≤ 2.5 x institutional upper limit of normal (ULN)
- ALT (SGPT) ≤ 2.5 x institutional upper limit of normal (ULN)
- Must have the ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Prior treatment for rectal cancer or prior radiation for other diagnoses to the expected rectal cancer treatment fields.
- Participants receiving any other investigational agents.
- Unresectable primary tumor or unresectable metastatic disease as determined by imaging.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to Pembrolizumab or other agents used in this study.
- Participants with uncontrolled intercurrent illness including, but not limited to:
- Ongoing or active infection
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- Known history of pneumonitis
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant or lactating females.
- Female participants who:
- Are postmenopausal for at least 1 year before the screening visit, OR
- Are surgically sterile, OR
- Agree to practice true abstinence from heterosexual contact or agree to use effective contraception without interruption during the study therapy and 90 days after the last dose
- Male participants who: Are surgically sterile, OR Agree to practice true abstinence from heterosexual contact or agree to use effective contraception without interruption during the study therapy and 90 days after the last dose
- HIV-positive participants on combination antiretroviral therapy, participants with active Hepatitis B or C, active tuberculosis, or administration of live vaccine within 30 days of planned start of study therapy will be excluded.
- Participants with a diagnosis of immunodeficiency, active autoimmune disease (including inflammatory bowel disease) or those receiving immunosuppressive therapy within 7 days (other than Prednisone ≤ 5mg daily) prior to the planned start of study treatment will be excluded.
Trial locations and contacts
1 site in 1 country.
United States1 site
Cleveland Clinic, Case Comprehensive Cancer Center
Cleveland, Ohio, 44122
About this study
Official title: Neoadjuvant Immunotherapy in Rectal Cancer: A Pilot Study Examining the Safety and Feasibility of PD-1 Blockade in the Treatment of dMMR or MSI-H Rectal Cancer
Colorectal cancer is the third most common cancer worldwide and the second leading cause of cancer mortality in the United States. The current standard of care (SOC) for locally advanced rectal cancer includes neoadjuvant chemotherapy and radiation followed by surgery. However, great variability exists in patient's response to neoadjuvant chemoradiotherapy with only about 20-25% of patients achieving a complete response while other patients achieve a partial or no treatment response. The purpose of this study is to test the investigational agent, Pembrolizumab, in combination with SOC radiation and Capecitabine (or 5-Fluorouacil) in treatment of patients with mismatch repair deficient locally advanced rectal cancer.
Read the detailed description
This study investigates the safety, tolerability, and feasibility of Pembrolizumab, an immunotherapy agent, in combination with SOC radiation and Capecitabine (or 5-Fluorouacil) in treatment of patients with mismatch repair deficient locally advanced rectal cancer. Pembrolizumab is an investigational (experimental) drug that works by enhancing the functional activity of the target lymphocytes (immune cells) to facilitate tumor regression and ultimately immune rejection. Pembrolizumab in combination with radiation and Capcitabine (or 5-Fluorouacil) is experimental because it is not approved by the Food and Drug Administration (FDA) for this specific indication.
The primary objective of this study is to determine the safety, tolerability and feasibility of neoadjuvant pembrolizumab in combination with capectiabine (or 5-Fluorouracil ) in the treatment of patients with MMR-d locally advanced rectal cancer
The secondary objective of this study is to determine the treatment response in MMR-d rectal cancer patients treated with neoadjuvant chemoradiotherapy and Pembrolizumab.
- Conditions
- Rectal Neoplasms
- Being tested
- Pembrolizumab, External beam radiation, Capecitabine
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
200 mg intravenously (IV) on days 1, 22, and 43
External beam radiationRadiation
Daily fractions of 200 cGy, 5 days a week for the first 5 weeks of the study, excluding weekends
CapecitabineDrug
825 mg/m2 orally twice a day on days where radiation therapy is given
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab | Experimental | Experimental pembrolizumab and SOC external beam radiation and capecitabine Receives: Drug: Pembrolizumab; Radiation: External beam radiation; Drug: Capecitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of adverse events (AEs) as defined by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Safety endpoint will be defined by rate of AEs as defined by the CTCAE v5.0
Measured: 30 days after intervention
Proportion of participants able to complete planned neoadjuvant treatment protocol
Tolerability as defined by proportion of participants that are able to complete the planned neoadjuvant treatment protocol
Measured: 45 days after intervention
Feasibility as defined by proportion of participants with any delay in planned surgery of more than 30 days
Feasibility as defined by proportion of participants with any delay in the planned surgery of more than 30 days
Measured: 115 days after intervention
Treatment response as measured by AJCC tumor regression grade (TRG)
Treatment response as measured by pathologic assessment of treatment response using the AJCC TRG following surgical resection.
AJCC TRG grading ranges from 0-3:
0 (complete response): no viable cancer cells
- (near complete response): single cells or rare small groups of cancer cells
- (partial response): residual cancer with evident tumor regression but more than single cells or rare small groups of cancer cells
- (poor or no response): extensive residual cancer with no evident tumor regression.
Measured: at time of surgical resection, an average of 10 weeks after radiation
Treatment response as measured by MRI tumor regression grade
Treatment response as measured by MRI tumor regression grade.
The MRI tumor regression grade uses the following scale:
- No/minimal fibrosis visible (tiny linear scar) and no tumor signal
- Dense fibrotic scar (low signal intensity) but no macroscopic tumor signal (indicates no or microscopic tumor)
- Fibrosis predominates but obvious measurable areas of tumor signal visible
- Tumor signal predominates with little/minimal fibrosis
- Tumor signal only: no fibrosis, includes progression of tumor
Measured: 4-6 weeks before intervention
Treatment response as measured by Carcinoembryonic antigen (CEA) blood test
Treatment response as measured by CEA levels
Measured: 4-6 weeks before intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2020
- Study start6 Aug 2020
- Primary completion25 Sep 2023
- Study completion25 Sep 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rectal NeoplasmsStudies of the same condition, open and under way.
- More trials run by Case Comprehensive Cancer CenterThe 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Case Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- David Liska, MD, Principal investigator, Cleveland Clinic, Case Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04357587
- Sponsor's protocol ID
- CASE1220
- Status last verified
- May 2024
- First submitted
- 20 Apr 2020
- Last updated
- 29 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neoadjuvant Immunotherapy in Rectal Cancer: A Pilot Study Examining the Safety and Feasibility of PD-1 Blockade in the Treatment of dMMR or MSI-H Rectal Cancer
- ClinicalTrials.gov ID
- NCT04357587
- Acronym / sponsor ID
- CASE1220
- Conditions
- Rectal Neoplasms
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Case Comprehensive Cancer CenterUniversity, hospital or other
- Study start
- 6 Aug 2020 (actual)
- Primary completion
- 25 Sep 2023 (actual)
- Study completion
- 25 Sep 2023 (actual)
- First posted
- 22 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Colorectal cancer is the third most common cancer worldwide and the second leading cause of cancer mortality in the United States. The current standard of care (SOC) for locally advanced rectal cancer includes neoadjuvant chemotherapy and radiation followed by surgery. However, great variability exists in patient's response to neoadjuvant chemoradiotherapy with only about 20-25% of patients achieving a complete response while other patients achieve a partial or no treatment response. The purpose of this study is to test the investigational agent, Pembrolizumab, in combination with SOC radiation and Capecitabine (or 5-Fluorouacil) in treatment of patients with mismatch repair deficient locally advanced rectal cancer.
Detailed description
This study investigates the safety, tolerability, and feasibility of Pembrolizumab, an immunotherapy agent, in combination with SOC radiation and Capecitabine (or 5-Fluorouacil) in treatment of patients with mismatch repair deficient locally advanced rectal cancer. Pembrolizumab is an investigational (experimental) drug that works by enhancing the functional activity of the target lymphocytes (immune cells) to facilitate tumor regression and ultimately immune rejection. Pembrolizumab in combination with radiation and Capcitabine (or 5-Fluorouacil) is experimental because it is not approved by the Food and Drug Administration (FDA) for this specific indication.
The primary objective of this study is to determine the safety, tolerability and feasibility of neoadjuvant pembrolizumab in combination with capectiabine (or 5-Fluorouracil ) in the treatment of patients with MMR-d locally advanced rectal cancer
The secondary objective of this study is to determine the treatment response in MMR-d rectal cancer patients treated with neoadjuvant chemoradiotherapy and Pembrolizumab.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab | Experimental | Drug: Pembrolizumab, Radiation: External beam radiation, Drug: CapecitabineExperimental pembrolizumab and SOC external beam radiation and capecitabine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Must have confirmed rectal adenocarcinoma Defined as, MRI based clinical stage II (T3-4, N0), stage III (T1-4, N+), or oligometastatic locally advanced stage IV that are candidates for curative surgery
- Tumor location at and/or below the peritoneal reflection on MRI.
- Review and discussion at multidisciplinary tumor board with consensus recommendation for neoadjuvant chemoradiation followed by curative-intent surgery. Documented in EPIC tumor board.
- MMR-deficiency confirmed on immunohistochemistry or MSI status confirmed by PCR.
- ECOG Performance status 0-1
Key exclusion criteria (19 listed)
- Prior treatment for rectal cancer or prior radiation for other diagnoses to the expected rectal cancer treatment fields.
- Participants receiving any other investigational agents.
- Unresectable primary tumor or unresectable metastatic disease as determined by imaging.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to Pembrolizumab or other agents used in this study.
- Participants with uncontrolled intercurrent illness including, but not limited to:
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 |
|---|---|---|
| Pembrolizumab200 mg intravenously (IV) on days 1, 22, and 43 | Drug | Pembrolizumab |
| External beam radiationDaily fractions of 200 cGy, 5 days a week for the first 5 weeks of the study, excluding weekends | Radiation | Pembrolizumab |
| Capecitabine825 mg/m2 orally twice a day on days where radiation therapy is given | Drug | Pembrolizumab |
Primary outcome
Rate of adverse events (AEs) as defined by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Time frame: 30 days after intervention
Safety endpoint will be defined by rate of AEs as defined by the CTCAE v5.0
Proportion of participants able to complete planned neoadjuvant treatment protocol
Time frame: 45 days after intervention
Tolerability as defined by proportion of participants that are able to complete the planned neoadjuvant treatment protocol
Feasibility as defined by proportion of participants with any delay in planned surgery of more than 30 days
Time frame: 115 days after intervention
Feasibility as defined by proportion of participants with any delay in the planned surgery of more than 30 days
Treatment response as measured by AJCC tumor regression grade (TRG)
Time frame: at time of surgical resection, an average of 10 weeks after radiation
Treatment response as measured by pathologic assessment of treatment response using the AJCC TRG following surgical resection. AJCC TRG grading ranges from 0-3: 0 (complete response): no viable cancer cells 1. (near complete response): single cells or rare small groups of cancer cells 2. (partial response): residual cancer with evident tumor regression but more than single cells or rare small groups of cancer cells 3. (poor or no response): extensive residual cancer with no evident tumor regression.
Treatment response as measured by MRI tumor regression grade
Time frame: 4-6 weeks before intervention
Treatment response as measured by MRI tumor regression grade. The MRI tumor regression grade uses the following scale: 1. No/minimal fibrosis visible (tiny linear scar) and no tumor signal 2. Dense fibrotic scar (low signal intensity) but no macroscopic tumor signal (indicates no or microscopic tumor) 3. Fibrosis predominates but obvious measurable areas of tumor signal visible 4. Tumor signal predominates with little/minimal fibrosis 5. Tumor signal only: no fibrosis, includes progression of tumor
Treatment response as measured by Carcinoembryonic antigen (CEA) blood test
Time frame: 4-6 weeks before intervention
Treatment response as measured by CEA levels
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2024.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
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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.
David Liska, MD principal investigator
Cleveland Clinic, Case Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Pembrolizumab, External beam radiation and Capecitabine in people with Rectal Neoplasms, run by Case Comprehensive Cancer Center 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 15 inclusion and 19 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 29 May 2024. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Rate of adverse events (AEs) as defined by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 (time frame: 30 days after intervention). The study lists 6 primary outcomes in all. 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 29 May 2024.