Metastatic Colorectal CancerPhase 1NCT03176264
PDR001 in Combination With Bevacizumab and mFOLFOX6 as First Line Therapy in Patients With Metastatic MSS Colorectal Cancer
A Phase 1 study testing PDR001, bevacizumab and mFOLFOX6 in people with Metastatic Colorectal Cancer, run by Novartis Pharmaceuticals at 1 site in United Kingdom.
Trial summary
This was a phase Ib study of PDR001 in combination with bevacizumab and mFOLFOX6 as first line therapy in patients with metastatic microsatellite stable (MSS) colorectal cancer. The study was to have assessed primarily, the safety and tolerability and then the efficacy of PDR001 in combination with bevacizumab and… 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?
- PDR001, bevacizumab and mFOLFOX6
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 25 Sep 2017to 30 Jan 2018
- 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
- Patients with metastatic MSS colorectal adenocarcinoma.Note: MSI status will be performed locally by an immunohistochemistry (IHC) or PCR based test for eligibility.
- Patients must provide a newly obtained or an archival tumor sample corresponding to CRC diagnosis (primary tumor) with sufficient tissue quality (qualified) for analysis (mandatory)
- Patients must provide a newly obtained tumor tissue sample from a metastatic site (mandatory)
- Patients who are naïve to systemic treatment in metastatic setting. Patients with previous neoadjuvant or adjuvant chemotherapy (that may have included oxaliplatin or investigational VEGF inhibitors) are eligible if the treatment was completed > 12 months before inclusion.
- Patients with the presence of at least one lesion with measurable disease as per RECIST 1.1 guidelines. Lesions in previously irradiated areas should not be considered measurable unless they have clearly progressed since the radiotherapy.
- 9. Patients have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Who cannot join
- Patients with MSI-H colorectal adenocarcinoma as defined per local assessment using standard of care testing
- Patients with metastatic disease amenable to be resected with potentially curative surgery
- Patients who have received any systemic treatment for metastatic disease.
- Patients with a history of prior treatment with anti-PD-1, anti-PD-L1, anti-PDL2, anti-CTLA-4 antibodies, other checkpoint inhibitors
- Patients who had received radiation within 14 days prior to the first dose of study drug
- Other protocol-defined inclusion/exclusion criteria may apply
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Novartis Investigative Site
Sutton, Surrey, SM2 5PT
About this study
Official title: ElevatION: CRC-101: A Phase Ib Study of PDR001 in Combination With Bevacizumab and mFOLFOX6 as First Line Therapy in Patients With Metastatic MSS Colorectal Cancer
This was a phase Ib study of PDR001 in combination with bevacizumab and mFOLFOX6 as first line therapy in patients with metastatic microsatellite stable (MSS) colorectal cancer. The study was to have assessed primarily, the safety and tolerability and then the efficacy of PDR001 in combination with bevacizumab and mFOLFOX6. Particular attention would have been paid to the level of activity of study drug combinations in CMS4 patients (retrospective analysis).
The study was terminated early due to company decision.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- PDR001, bevacizumab, mFOLFOX6
- Keywords
- PDR001, immunotherapy, bevacizumab, mFOLFOX6, CRC, MMS, CMS4, ElevatION;CRC-101
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PDR001Drug
400 mg every 4 weeks
bevacizumabDrug
5 mg/kg every 2 weeks
mFOLFOX6Drug
Combination of chemotherapy administered every 2 weeks: oxaliplatin (85mg/m2), 5-Fluorouracil (2400mg/m2) and folinic acid (=leucovorin, 400mg/m2)
| Study group | Role | What they receive |
|---|---|---|
| PDR001 | Experimental | Not described Receives: Drug: PDR001; Drug: bevacizumab; Drug: mFOLFOX6 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Dose-limiting toxicity (DLT)
Measured: 12 months
Overall Response Rate (ORR) per investigator assessment using RECIST v1.1
RECIST v1.1 = Response Evaluation Criteria in Solid Tumors v1.1
Measured: 19 months
Secondary outcomes (10)
Overall response rate (ORR) per central assessment using RECIST v1.1
Measured: Baseline, every 8 weeks until progression per central assessment up to 1 year after last patient last visit
Overall survival (OS)
Measured: Every 3 months after last visit up to 1 year after last patient last visit
Progression free survival
Measured: Baseline, every 8 weeks until progression per central assessment up to 1 year after last patient last visit
Duration of response (DOR)
Measured: Baseline, every 8 weeks until progression per central assessment up to 1 year after last patient last visit
Disease control rate (DCR)
Measured: Baseline, every 8 weeks until progression per central assessment up to 1 year after last patient last visit
Time to response (TTR)
Measured: Baseline, every 8 weeks until progression per central assessment up to 1 year after last patient last visit
Ctrough
Measured: Through end of treatment completion, an average of 14 months
Cmax
Measured: Through end of treatment completion, an average of 14 months
Area under the curve (AUC)
Measured: Through end of treatment completion, an average of 14 months
Antidrug antibodies (ADA)
Measured: Through end of treatment completion, an average of 14 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2017
- Study start25 Sep 2017
- Primary completion30 Jan 2018
- Study completion30 Jan 2018
Why it stopped: The study was terminated early due to company decision.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe 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
- Model description
- Phase Ib study, safety run-in (N=\~6 pts) followed with an expansion (N=\~86 pts). One single arm: PDR001 in combination with bevacizumab and mFOLFOX6
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Principal investigator, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03176264
- Sponsor's protocol ID
- CPDR001I2101
- Other IDs
- 2017-000520-96, 2017
- Status last verified
- Oct 2021
- First submitted
- 25 May 2017
- Last updated
- 12 Oct 2021
- Results posted
- No
- 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 12 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ElevatION: CRC-101: A Phase Ib Study of PDR001 in Combination With Bevacizumab and mFOLFOX6 as First Line Therapy in Patients With Metastatic MSS Colorectal Cancer
- ClinicalTrials.gov ID
- NCT03176264
- Acronym / sponsor ID
- CPDR001I2101
- Conditions
- Metastatic Colorectal Cancer
- Keywords
- PDR001, immunotherapy, bevacizumab, mFOLFOX6, CRC, MMS, CMS4, ElevatION;CRC-101
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated early due to company decision.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 25 Sep 2017 (actual)
- Primary completion
- 30 Jan 2018 (actual)
- Study completion
- 30 Jan 2018 (actual)
- First posted
- 5 Jun 2017 (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.
This was a phase Ib study of PDR001 in combination with bevacizumab and mFOLFOX6 as first line therapy in patients with metastatic microsatellite stable (MSS) colorectal cancer. The study was to have assessed primarily, the safety and tolerability and then the efficacy of PDR001 in combination with bevacizumab and mFOLFOX6. Particular attention would have been paid to the level of activity of study drug combinations in CMS4 patients (retrospective analysis).
The study was terminated early due to company decision.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Phase Ib study, safety run-in (N=~6 pts) followed with an expansion (N=~86 pts). One single arm: PDR001 in combination with bevacizumab and mFOLFOX6
| Arm | Type | Receives |
|---|---|---|
| PDR001 | Experimental | Drug: PDR001, Drug: bevacizumab, Drug: mFOLFOX6 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients with metastatic MSS colorectal adenocarcinoma.Note: MSI status will be performed locally by an immunohistochemistry (IHC) or PCR based test for eligibility.
- Patients must provide a newly obtained or an archival tumor sample corresponding to CRC diagnosis (primary tumor) with sufficient tissue quality (qualified) for analysis (mandatory)
- Patients must provide a newly obtained tumor tissue sample from a metastatic site (mandatory)
- Patients who are naïve to systemic treatment in metastatic setting. Patients with previous neoadjuvant or adjuvant chemotherapy (that may have included oxaliplatin or investigational VEGF inhibitors) are eligible if the treatment was completed > 12 months before inclusion.
- Patients with the presence of at least one lesion with measurable disease as per RECIST 1.1 guidelines. Lesions in previously irradiated areas should not be considered measurable unless they have clearly progressed since the radiotherapy.
Key exclusion criteria (6 listed)
- Patients with MSI-H colorectal adenocarcinoma as defined per local assessment using standard of care testing
- Patients with metastatic disease amenable to be resected with potentially curative surgery
- Patients who have received any systemic treatment for metastatic disease.
- Patients with a history of prior treatment with anti-PD-1, anti-PD-L1, anti-PDL2, anti-CTLA-4 antibodies, other checkpoint inhibitors
- Patients who had received radiation within 14 days prior to the first dose of study drug
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 |
|---|---|---|
| PDR001400 mg every 4 weeks | Drug | PDR001 |
| bevacizumab5 mg/kg every 2 weeks | Drug | PDR001 |
| mFOLFOX6Combination of chemotherapy administered every 2 weeks: oxaliplatin (85mg/m2), 5-Fluorouracil (2400mg/m2) and folinic acid (=leucovorin, 400mg/m2) | Drug | PDR001 |
Primary outcome
Incidence of Dose-limiting toxicity (DLT)
Time frame: 12 months
Overall Response Rate (ORR) per investigator assessment using RECIST v1.1
Time frame: 19 months
RECIST v1.1 = Response Evaluation Criteria in Solid Tumors v1.1
10 secondary outcomes
Overall response rate (ORR) per central assessment using RECIST v1.1
Time frame: Baseline, every 8 weeks until progression per central assessment up to 1 year after last patient last visit
Overall survival (OS)
Time frame: Every 3 months after last visit up to 1 year after last patient last visit
Progression free survival
Time frame: Baseline, every 8 weeks until progression per central assessment up to 1 year after last patient last visit
Duration of response (DOR)
Time frame: Baseline, every 8 weeks until progression per central assessment up to 1 year after last patient last visit
Disease control rate (DCR)
Time frame: Baseline, every 8 weeks until progression per central assessment up to 1 year after last patient last visit
Time to response (TTR)
Time frame: Baseline, every 8 weeks until progression per central assessment up to 1 year after last patient last visit
Ctrough
Time frame: Through end of treatment completion, an average of 14 months
Cmax
Time frame: Through end of treatment completion, an average of 14 months
Area under the curve (AUC)
Time frame: Through end of treatment completion, an average of 14 months
Antidrug antibodies (ADA)
Time frame: Through end of treatment completion, an average of 14 months
Results and safety
The study was stopped early (reason given: The study was terminated early due to company decision.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2021.
- Novartis results databaseLink provided by the sponsor.
- A Plain Language Trial Summary is available on novartisclinicaltrials.comLink provided by the sponsor.
- 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.
Novartis Pharmaceuticals principal investigator
Novartis Pharmaceuticals
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 PDR001, bevacizumab and mFOLFOX6 in people with Metastatic Colorectal Cancer, run by Novartis Pharmaceuticals at 1 site in United Kingdom.
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 6 inclusion and 6 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 12 Oct 2021. 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 Kingdom. 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 was stopped early (reason given: The study was terminated early due to company decision.). Results are not available in the source record.
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?
Incidence of Dose-limiting toxicity (DLT) (time frame: 12 months). The study lists 2 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 12 Oct 2021.