Metastatic Colorectal CancerPhase 2NCT03122509
A Clinical Trial of Durvalumab and Tremelimumab, Administered With Radiation Therapy or Ablation in Patients With Colorectal Cancer
A Phase 2 study testing durvalumab, tremelimumab and Radiotherapy (RT) in people with Metastatic Colorectal Cancer, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
Trial summary
The purpose of this study is to test the safety and effectiveness of two investigational drugs (drugs that are not currently approved by the FDA) given in combination with radiation therapy or ablation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- durvalumab, tremelimumab and Radiotherapy (RT)
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Apr 2017to 28 Apr 2021
- 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.
- Histologically- or cytologically- confirmed CRC.
- Metastatic CRC.
- Subjects have received at least two standard chemotherapy regimens for which they would be considered eligible (at least one containing a 5-fluoropyrimidine), or systemic chemotherapy is not indicated in the setting of low volume metastatic disease.
- At least one tumor for which palliative RT is considered appropriate standard therapy (cohort 1); or, at least one tumor for which palliative ablation is considered appropriate standard therapy (cohort 2).
- At least one index lesion that will not undergo RT or ablation, and which is measurable based on RECIST 1.1.
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- Be ≥ 18 years of age on day of signing informed consent.
- Consent for tumor biopsies (for patients enrolled in stage 1 only) and blood draws for research purposes (for all patients).
- Consent for use of available archived tissue and tumor obtained during a standard procedure, for research purposes.
- Have a performance status of 0 or 1 on the ECOG Performance Scale.
- Female subjects must either be of non-reproductive potential (i.e., post-menopausal by history: ≥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 within 2 weeks prior to starting treatment.
- Demonstrate adequate organ function as defined all screening labs should be performed within 4 weeks prior to treatment initiation.
- Hemoglobin ≥ 8.0 g/dL
- Absolute neutrophil count (ANC) ≥1,500 /mcL
- Platelets ≥100,000 / mcL
- Serum creatinine ≤1.5 X upper limit of normal (ULN) OR
- Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) OR
- Serum creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance.
- Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN
- AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases.
- aCreatinine clearance should be calculated per institutional standard.
Who cannot join
- Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.
- Chemotherapy, monoclonal antibody, targeted small molecule therapy, within 4 weeks prior to dose #1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent (excluding alopecia or toxicity not anticipated to interfere with planned treatment on study).
- Known or suspected MSI-H CRC.
- Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1, including anti-PD-1, anti-PD-L1, anti-CD137, anti-CTLA-4 antibody or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways, except for endocrinopathies and asymptomatic amylase/lipase.
- If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention per clinical discretion of the investigator prior to starting therapy.
- Concurrent active malignancy that requires systemic treatment.
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- Known CNS metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable without evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. The use of topical steroids is permitted.
- Active autoimmune disease requiring systemic immune suppressive treatment within the past 2 years. NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
- Has active, non-infectious pneumonitis.
- Active or prior documented inflammatory bowel disease.
- History of allogeneic organ transplant.
- Has an active infection requiring systemic therapy.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
- Has known active and untreated Hepatitis B (e.g., HBsAg reactive) or active Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- Has received a live vaccine within 30 days prior to the first dose of trial treatment.
- Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab with the exceptions of premedication and intranasal, topical and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10mg/day of prednisone, or an equivalent corticosteroid.
- Hypersensitivity to durvalumab or tremelimumab, or any excipients on the formulation.
- Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results.
- Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 180 days after the last dose of durvalumab + tremelimumab combination therapy or 90 days after the last dose of durvalumab monotherapy, whichever is the longer time period.
- QT interval corrected for heart rate (QTc) ≥ 470ms calculated from 1 electrocardiogram (ECG) using Fridericia's Correction.
- History of primary immunodeficiency.
- Known history of previous clinical diagnosis of tuberculosis.
- Subjects with uncontrolled seizures.
Trial locations and contacts
1 site in 1 country.
United States1 site
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
About this study
Official title: Phase II Study to Assess the Efficacy of Durvalumab (MEDI4736) and Tremelimumab Plus Radiotherapy or Ablation in Patients With Metastatic Colorectal Cancer
The purpose of this study is to test the safety and effectiveness of two investigational drugs (drugs that are not currently approved by the FDA) given in combination with radiation therapy or ablation.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- durvalumab, tremelimumab, Radiotherapy (RT), ablation
- Keywords
- Durvalumab, Tremelimumab, Radiation Therapy, Ablation, 17-139
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
durvalumabDrug
Also called (MEDI4736)
1500 mg durvalumab via IV infusion
tremelimumabDrug
75 mg tremelimumab via IV infusion
Radiotherapy (RT)Radiation
Radiotherapy (RT) will be performed using external beam ionizing radiation as standard therapy in accordance with institutional standard practice.
ablationProcedure or surgery
Ablation will be performed percutaneously under image guidance as standard therapy at the discretion of the interventional radiologist in accordance with institutional standard practice.
| Study group | Role | What they receive |
|---|---|---|
| durvalumab and tremelimumab plus Radiotherapy (RT) | Experimental | Patients will receive 1500 mg durvalumab via IV infusion q4w for up to 4 doses/cycles and 75 mg tremelimumab via IV infusion q4w for up to 4 doses/cycles, and then continue 1500 mg durvalumab q4w starting on Week 16. Tremelimumab will be administered first. Durvalumab infusion will start approximately 1 hour after the end of tremelimumab infusion. The duration will be approximately 1 hour for each infusion. Radiotherapy (RT) will be performed using external beam ionizing radiation as standard therapy in accordance with institutional standard practice. RT will be initiated within 7 days after the first of durvalumab and tremelimumab. Receives: Drug: durvalumab; Drug: tremelimumab; Radiation: Radiotherapy (RT) |
| durvalumab and tremelimumab plus ablation | Experimental | Patients will receive 1500 mg durvalumab via IV infusion q4w for up to 4 doses/cycles and 75 mg tremelimumab via IV infusion q4w for up to 4 doses/cycles, and then continue 1500 mg durvalumab q4w starting on Week 16. Tremelimumab will be administered first. Durvalumab infusion will start approximately 1 hour after the end of tremelimumab infusion. The duration will be approximately 1 hour for each infusion. The ablation will be performed percutaneously under image guidance as standard therapy at the discretion of the interventional radiologist in accordance with institutional standard practice. Ablation will be performed within 7 days after the first of durvalumab and tremelimumab. Receives: Drug: durvalumab; Drug: tremelimumab; Procedure: ablation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2017
- Study start24 Apr 2017
- Primary completion28 Apr 2021
- Study completion28 Apr 2021
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 Metastatic Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- This will be a Simon two-stage design, phase II study. It will be conducted to determine the efficacy and safety of (1) durvalumab and tremelimumab plus RT in subjects with metastatic CRC who are undergoing RT as standard therapy; and, (2) durvalumab and tremelimumab plus ablation in subjects with metastatic CRC who are undergoing ablation as standard therapy.
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- MedImmune LLC, AstraZeneca
- Responsible party
- Sponsor
- Investigators
- Neil Segal, MD, PhD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03122509
- Sponsor's protocol ID
- 17-139
- Status last verified
- Apr 2021
- First submitted
- 18 Apr 2017
- Last updated
- 6 Jul 2022
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 6 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study to Assess the Efficacy of Durvalumab (MEDI4736) and Tremelimumab Plus Radiotherapy or Ablation in Patients With Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT03122509
- Acronym / sponsor ID
- 17-139
- Conditions
- Metastatic Colorectal Cancer
- Keywords
- Durvalumab, Tremelimumab, Radiation Therapy, Ablation, 17-139
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- MedImmune LLC, AstraZeneca
- Study start
- 24 Apr 2017 (actual)
- Primary completion
- 28 Apr 2021 (actual)
- Study completion
- 28 Apr 2021 (actual)
- First posted
- 20 Apr 2017 (actual)
- Results
- Posted 6 Jul 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to test the safety and effectiveness of two investigational drugs (drugs that are not currently approved by the FDA) given in combination with radiation therapy or ablation.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This will be a Simon two-stage design, phase II study. It will be conducted to determine the efficacy and safety of (1) durvalumab and tremelimumab plus RT in subjects with metastatic CRC who are undergoing RT as standard therapy; and, (2) durvalumab and tremelimumab plus ablation in subjects with metastatic CRC who are undergoing ablation as standard therapy.
| Arm | Type | Receives |
|---|---|---|
| durvalumab and tremelimumab plus Radiotherapy (RT) | Experimental | Drug: durvalumab, Drug: tremelimumab, Radiation: Radiotherapy (RT)Patients will receive 1500 mg durvalumab via IV infusion q4w for up to 4 doses/cycles and 75 mg tremelimumab via IV infusion q4w for up to 4 doses/cycles, and then continue 1500 mg durvalumab q4w starting on Week 16. Tremelimumab will be administered first. Durvalumab infusion will start approximately 1 hour after the end of tremelimumab infusion. The duration will be approximately 1 hour for each infusion. Radiotherapy (RT) will be performed using external beam ionizing radiation as standard therapy in accordance with institutional standard practice. RT will be initiated within 7 days after the first of durvalumab and tremelimumab. |
| durvalumab and tremelimumab plus ablation | Experimental | Drug: durvalumab, Drug: tremelimumab, Procedure: ablationPatients will receive 1500 mg durvalumab via IV infusion q4w for up to 4 doses/cycles and 75 mg tremelimumab via IV infusion q4w for up to 4 doses/cycles, and then continue 1500 mg durvalumab q4w starting on Week 16. Tremelimumab will be administered first. Durvalumab infusion will start approximately 1 hour after the end of tremelimumab infusion. The duration will be approximately 1 hour for each infusion. The ablation will be performed percutaneously under image guidance as standard therapy at the discretion of the interventional radiologist in accordance with institutional standard practice. Ablation will be performed within 7 days after the first of durvalumab and tremelimumab. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Be willing and able to provide written informed consent for the trial.
- Histologically- or cytologically- confirmed CRC.
- Metastatic CRC.
- Subjects have received at least two standard chemotherapy regimens for which they would be considered eligible (at least one containing a 5-fluoropyrimidine), or systemic chemotherapy is not indicated in the setting of low volume metastatic disease.
- At least one tumor for which palliative RT is considered appropriate standard therapy (cohort 1); or, at least one tumor for which palliative ablation is considered appropriate standard therapy (cohort 2).
Key exclusion criteria (24 listed)
- Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.
- Chemotherapy, monoclonal antibody, targeted small molecule therapy, within 4 weeks prior to dose #1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent (excluding alopecia or toxicity not anticipated to interfere with planned treatment on study).
- Known or suspected MSI-H CRC.
- Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1, including anti-PD-1, anti-PD-L1, anti-CD137, anti-CTLA-4 antibody or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways, except for endocrinopathies and asymptomatic amylase/lipase.
- If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention per clinical discretion of the investigator prior to starting therapy.
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 |
|---|---|---|
| durvalumabAlso: (MEDI4736)1500 mg durvalumab via IV infusion | Drug | durvalumab and tremelimumab plus Radiotherapy (RT), durvalumab and tremelimumab plus ablation |
| tremelimumab75 mg tremelimumab via IV infusion | Drug | durvalumab and tremelimumab plus Radiotherapy (RT), durvalumab and tremelimumab plus ablation |
| Radiotherapy (RT)Radiotherapy (RT) will be performed using external beam ionizing radiation as standard therapy in accordance with institutional standard practice. | Radiation | durvalumab and tremelimumab plus Radiotherapy (RT) |
| ablationAblation will be performed percutaneously under image guidance as standard therapy at the discretion of the interventional radiologist in accordance with institutional standard practice. | Procedure or surgery | durvalumab and tremelimumab plus ablation |
Primary outcome
Overall Response Rate
Time frame: 2 years
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jul 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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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.
Neil Segal, MD, PhD principal investigator
Memorial Sloan Kettering 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 2 study testing durvalumab, tremelimumab and Radiotherapy (RT) in people with Metastatic Colorectal Cancer, run by Memorial Sloan Kettering 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 21 inclusion and 24 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 6 Jul 2022. 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 6 Jul 2022). 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?
Overall Response Rate (time frame: 2 years). 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 6 Jul 2022.