Mucinous Adenocarcinoma of the ColonPhase 2NCT03693846
Nivolumab and Ipilimumab in Mucinous Colorectal and Appendiceal Tumors
A Phase 2 study testing Nivolumab and Ipilimumab in people with Mucinous Adenocarcinoma of the Colon and Mucinous Adenocarcinoma of the Rectum, run by Abramson Cancer Center at Penn Medicine at 1 site in United States.
Trial summary
This is a single-arm phase II study of twenty-one subjects with mucinous adenocarcinoma of the colon, rectum, or appendix with prior systemic therapy with a fluoropyrimidine, oxaliplatin, and irinotecan. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mucinous Adenocarcinoma of the Colon, Mucinous Adenocarcinoma of the Rectum
- What is being tested?
- Nivolumab and Ipilimumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Feb 2019to 6 Mar 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
- Subjects must have signed and dated an IRB-approved written informed consent form prior to the performance of any protocol-related procedures that are not part of standard care.
- Colorectal or appendiceal mucinous adenocarcinoma with peritoneal-only metastatic disease. It is recognized that in some patients, peritoneal disease will predominate without distinction of the site of origin, and such patients will be eligible.
- Microsatellite stable by PCR and/or mismatch repair proficient by immunohistochemistry
- ECOG performance status of 0 or 1
- Prior therapy with a fluoropyrimidine, oxaliplatin, and irinotecan unless contraindicated or refused. Prior treatment with antiangiogenic and/or anti-EGFR antibody therapy is permitted but not required
- Measurable disease by RECIST v. 1.1
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- Laboratory parameters:
- Absolute neutrophil count > 1500/μL
- Platelets > 100,000/μL
- Hemoglobin > 9.0 g/dL
- PT/INR or PTT < 1.5xULN
- Creatinine < 1.5xULN OR creatinine clearance > 50 mL/min by Cockcroft-Gault formula
- Total bilirubin < 1.5xULN
- Subjects with Gilbert's Syndrome must have a total bilirubin level of < 3.0xULN
- Albumin > 3.0 g/dL
- AST and/or ALT: < 3.0×ULN
- Subjects with HIV are permitted provided they meet the following criteria:
- CD4+ cell count > 250 cells/mm3
- No history of AIDS-defining conditions other than low CD4+ count
- If subject is on antiretroviral therapy, there must not be expected significant drug-drug interactions with study treatment
Who cannot join
- Bowel obstruction within the past 60 days
- Subjects who are currently pregnant, planning to become pregnant, or breast-feeding.
- Females participants of child-bearing potential are required to use an effective contraception method or abstain from intercourse during treatment and for at least 5 months following the last dose
- Males participants with partners of child-bearing potential are required to use an effective contraception method or abstain from intercourse during treatment and for at least 7 months following the last dose
- Subjects who, in the opinion of the physician, would not be clinically appropriate for receipt of the therapy regimen associated with participation
- Subjects with contraindications to immune checkpoint therapy, as follows:
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- Interstitial lung disease that is symptomatic or may interfere with the detection and management of suspected drug-related pulmonary toxicity
- Prior organ allograft or allogeneic bone marrow transplantation
- Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication
- Active autoimmune disease, except for vitiligo, type 1 diabetes mellitus, asthma, atopic dermatitis, or endocrinopathies manageable by hormone replacement; other autoimmune conditions may be allowable at the discretion of the principal investigator
- Condition requiring systemic treatment with corticosteroids
- Systemic steroids at physiologic doses (equivalent to dose of oral prednisone 10 mg) are permitted.
- Intranasal, inhaled, topical, intra-articular, and ocular corticosteroids with minimal systemic absorption are permitted.
- Established non-peritoneal metastatic disease, including but not limited to metastases to the liver, lung, brain, extra-abdominal lymph nodes, and bone
- A second primary malignancy that, in the judgment of the investigator, may affect interpretation of results
- Prior treatment with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody
- Toxicities attributed to prior anti-cancer therapy other than alopecia, fatigue, and peripheral neuropathy must have resolved to Grade 1 or baseline before administration of study drug. In addition, a washout period will be required for prior therapies as specified:
- No chemotherapy within 14 days prior to first dose
- No investigational product(s) (IPs) and/or biologic therapy within 28 days or 5 half-lives, whichever is longer, prior to first dose
- No major surgery within 28 days prior to first dose. Any surgery-related AE(s) must have resolved at least 14 days prior to first dose.
- No radiation therapy with curative intent within 28 days prior to first dose. Prior focal palliative radiotherapy must have been completed at least 14 days prior to first dose.
- Active hepatitis B or hepatitis C, defined as the following:
- Hepatitis B surface antigen positive or HBV DNA PCR >100 IU/mL
- Hepatitis C antibody positive unless HCV RNA PCR is negative (i.e. undetectable viral load)
- Prisoners or participants who are involuntarily incarcerated. (Note: under specific circumstances a person who has been imprisoned may be included as a participant. Strict conditions apply and BMS approval is required.)
- Participants who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness
Trial locations and contacts
1 site in 1 country.
United States1 site
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: A Phase II Study of Nivolumab and Ipilimumab in Mucinous Colorectal and Appendiceal Tumors
This is a single-arm phase II study of twenty-one subjects with mucinous adenocarcinoma of the colon, rectum, or appendix with prior systemic therapy with a fluoropyrimidine, oxaliplatin, and irinotecan. Treatment will consist of nivolumab 480mg every 4 weeks and ipilimumab 1mg/kg every 8 weeks until disease progression, unacceptable toxicity, or 2 years of therapy.
Read the detailed description
Treatment will consist of nivolumab 480mg every 4 weeks and ipilimumab 1mg/kg every 8 weeks (within a 56-day cycle, (Nivolumab administered on days 1 and 29, and Ipilimumab administered on day 1 of each cycle). Imaging assessments will be conducted every 8 weeks (+/-2 weeks) for the first 24 weeks then every 8-12 weeks (+/-2 weeks). If progression is noted on imaging in the setting of clinical stability, subjects may remain on study and have confirmatory imaging in 4-8 weeks per iRECIST criteria
- Being tested
- Nivolumab, Ipilimumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabDrug
Also called Opdivo
IV infusion per institutional guidelines and the Package Insert
IpilimumabDrug
Also called Yervoy
IV infusion per institutional guidelines and the Package Insert
| Study group | Role | What they receive |
|---|---|---|
| Nivolumab and Ipilimumab | Experimental | Treatment will consist of Nivolumab 480mg every 4 weeks and Ipilimumab 1mg/kg every 8 weeks. Subjects will continue on study therapy until disease progression, unacceptable toxicity, withdrawal of consent, or 24 months of therapy. Receives: Drug: Nivolumab; Drug: Ipilimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Progression-Free Survival at 6 Months
To determine six-month progression-free survival by iRECIST from start of study treatment until 6 months
Measured: Start of treatment until 6 months later
Secondary outcomes (4)
Progression-Free Survival
to determine Progression-Free survival from start of study treatment until time of documented disease progression or death assessed up to 2 years
Measured: start of treatment until disease progression or death, assessed up to 2 years
Overall Survival
Overall survival (OS) is defined as the duration of time from start of treatment to death
Measured: From start of treatment until death assessed up to 2 years
Objective Response Rate
The objective response rate is determined by the percentage of individuals on study attaining a complete or partial response as noted by by iRECIST and RECIST v1.1 Criteria
Measured: From start of treatment until progression or death assessed up to 2 years
Duration of Response
Time from the first recorded partial or complete response using RECIST v.1.1 criteria until disease progression or death
Measured: From the first recorded partial or complete response until progressive disease or death, whichever came first, assessed up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2018
- Study start15 Feb 2019
- Primary completion6 Mar 2021
- Study completion6 Mar 2021
Why it stopped: Terminated due to slow enrollment and lack of efficacy
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 Mucinous Adenocarcinoma of the ColonStudies of the same condition, open and under way.
- More trials run by Abramson Cancer Center at Penn MedicineThe 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
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Abramson Cancer Center at Penn Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Thomas Karasic, MD, Principal investigator, Abramson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03693846
- Sponsor's protocol ID
- UPCC 28218
- Status last verified
- Sep 2022
- First submitted
- 1 Oct 2018
- Last updated
- 20 Oct 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- 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 20 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Nivolumab and Ipilimumab in Mucinous Colorectal and Appendiceal Tumors
- ClinicalTrials.gov ID
- NCT03693846
- Acronym / sponsor ID
- UPCC 28218
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated due to slow enrollment and lack of efficacy
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Abramson Cancer Center at Penn MedicineUniversity, hospital or other
- Study start
- 15 Feb 2019 (actual)
- Primary completion
- 6 Mar 2021 (actual)
- Study completion
- 6 Mar 2021 (actual)
- First posted
- 3 Oct 2018 (actual)
- Results
- Posted 20 Oct 2022
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-arm phase II study of twenty-one subjects with mucinous adenocarcinoma of the colon, rectum, or appendix with prior systemic therapy with a fluoropyrimidine, oxaliplatin, and irinotecan. Treatment will consist of nivolumab 480mg every 4 weeks and ipilimumab 1mg/kg every 8 weeks until disease progression, unacceptable toxicity, or 2 years of therapy.
Detailed description
Treatment will consist of nivolumab 480mg every 4 weeks and ipilimumab 1mg/kg every 8 weeks (within a 56-day cycle, (Nivolumab administered on days 1 and 29, and Ipilimumab administered on day 1 of each cycle). Imaging assessments will be conducted every 8 weeks (+/-2 weeks) for the first 24 weeks then every 8-12 weeks (+/-2 weeks). If progression is noted on imaging in the setting of clinical stability, subjects may remain on study and have confirmatory imaging in 4-8 weeks per iRECIST criteria
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nivolumab and Ipilimumab | Experimental | Drug: Nivolumab, Drug: IpilimumabTreatment will consist of Nivolumab 480mg every 4 weeks and Ipilimumab 1mg/kg every 8 weeks. Subjects will continue on study therapy until disease progression, unacceptable toxicity, withdrawal of consent, or 24 months of therapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Subjects must have signed and dated an IRB-approved written informed consent form prior to the performance of any protocol-related procedures that are not part of standard care.
- Colorectal or appendiceal mucinous adenocarcinoma with peritoneal-only metastatic disease. It is recognized that in some patients, peritoneal disease will predominate without distinction of the site of origin, and such patients will be eligible.
- Microsatellite stable by PCR and/or mismatch repair proficient by immunohistochemistry
- ECOG performance status of 0 or 1
- Prior therapy with a fluoropyrimidine, oxaliplatin, and irinotecan unless contraindicated or refused. Prior treatment with antiangiogenic and/or anti-EGFR antibody therapy is permitted but not required
Key exclusion criteria (26 listed)
- Bowel obstruction within the past 60 days
- Subjects who are currently pregnant, planning to become pregnant, or breast-feeding.
- Subjects who, in the opinion of the physician, would not be clinically appropriate for receipt of the therapy regimen associated with participation
- Subjects with contraindications to immune checkpoint therapy, as follows:
- Established non-peritoneal metastatic disease, including but not limited to metastases to the liver, lung, brain, extra-abdominal lymph nodes, and bone
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 |
|---|---|---|
| NivolumabAlso: OpdivoIV infusion per institutional guidelines and the Package Insert | Drug | Nivolumab and Ipilimumab |
| IpilimumabAlso: YervoyIV infusion per institutional guidelines and the Package Insert | Drug | Nivolumab and Ipilimumab |
Primary outcome
Number of Participants With Progression-Free Survival at 6 Months
Time frame: Start of treatment until 6 months later
To determine six-month progression-free survival by iRECIST from start of study treatment until 6 months
4 secondary outcomes
Progression-Free Survival
Time frame: start of treatment until disease progression or death, assessed up to 2 years
Overall Survival
Time frame: From start of treatment until death assessed up to 2 years
Objective Response Rate
Time frame: From start of treatment until progression or death assessed up to 2 years
Duration of Response
Time frame: From the first recorded partial or complete response until progressive disease or death, whichever came first, assessed up to 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Thomas Karasic, MD principal investigator
Abramson 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 Nivolumab and Ipilimumab in people with Mucinous Adenocarcinoma of the Colon and Mucinous Adenocarcinoma of the Rectum, run by Abramson Cancer Center at Penn Medicine 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 20 inclusion and 26 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: stopped early, as of the sponsor's last update on 20 Oct 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 20 Oct 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?
Number of Participants With Progression-Free Survival at 6 Months (time frame: Start of treatment until 6 months later). 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 20 Oct 2022.