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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03176264




Registration number
NCT03176264
Ethics application status
Date submitted
25/05/2017
Date registered
5/06/2017
Date last updated
9/10/2019

Titles & IDs
Public title
PDR001 in Combination With Bevacizumab and mFOLFOX6 as First Line Therapy in Patients With Metastatic MSS Colorectal Cancer
Scientific 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
Secondary ID [1] 0 0
2017-000520-96
Secondary ID [2] 0 0
CPDR001I2101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Colorectal Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - PDR001
Treatment: Drugs - bevacizumab
Treatment: Drugs - mFOLFOX6

Experimental: PDR001 -


Treatment: Drugs: PDR001
400 mg every 4 weeks

Treatment: Drugs: bevacizumab
5 mg/kg every 2 weeks

Treatment: Drugs: mFOLFOX6
Combination of chemotherapy administered every 2 weeks: oxaliplatin (85mg/m2), 5-Fluorouracil (2400mg/m2) and folinic acid (=leucovorin, 400mg/m2)

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of Dose-limiting toxicity (DLT)
Timepoint [1] 0 0
12 months
Primary outcome [2] 0 0
Overall Response Rate (ORR) per investigator assessment using RECIST v1.1 - RECIST v1.1 = Response Evaluation Criteria in Solid Tumors v1.1
Timepoint [2] 0 0
19 months
Secondary outcome [1] 0 0
Overall response rate (ORR) per central assessment using RECIST v1.1
Timepoint [1] 0 0
Baseline, every 8 weeks until progression per central assessment up to 1 year after last patient last visit
Secondary outcome [2] 0 0
Overall survival (OS)
Timepoint [2] 0 0
Every 3 months after last visit up to 1 year after last patient last visit
Secondary outcome [3] 0 0
Progression free survival
Timepoint [3] 0 0
Baseline, every 8 weeks until progression per central assessment up to 1 year after last patient last visit
Secondary outcome [4] 0 0
Duration of response (DOR)
Timepoint [4] 0 0
Baseline, every 8 weeks until progression per central assessment up to 1 year after last patient last visit
Secondary outcome [5] 0 0
Disease control rate (DCR)
Timepoint [5] 0 0
Baseline, every 8 weeks until progression per central assessment up to 1 year after last patient last visit
Secondary outcome [6] 0 0
Time to response (TTR)
Timepoint [6] 0 0
Baseline, every 8 weeks until progression per central assessment up to 1 year after last patient last visit
Secondary outcome [7] 0 0
Ctrough
Timepoint [7] 0 0
Through end of treatment completion, an average of 14 months
Secondary outcome [8] 0 0
Cmax
Timepoint [8] 0 0
Through end of treatment completion, an average of 14 months
Secondary outcome [9] 0 0
Area under the curve (AUC)
Timepoint [9] 0 0
Through end of treatment completion, an average of 14 months
Secondary outcome [10] 0 0
Antidrug antibodies (ADA)
Timepoint [10] 0 0
Through end of treatment completion, an average of 14 months

Eligibility
Key inclusion criteria
Key inclusion criteria:

1. Patients with metastatic MSS colorectal adenocarcinoma.Note: MSI status will be
performed locally by an immunohistochemistry (IHC) or PCR based test for eligibility.

2. 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)

3. Patients must provide a newly obtained tumor tissue sample from a metastatic site
(mandatory)

4. 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.

5. 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

Key exclusion criteria:

1. Patients with MSI-H colorectal adenocarcinoma as defined per local assessment using
standard of care testing

2. Patients with metastatic disease amenable to be resected with potentially curative
surgery

3. Patients who have received any systemic treatment for metastatic disease.

4. Patients with a history of prior treatment with anti-PD-1, anti-PD-L1, anti-PDL2,
anti-CTLA-4 antibodies, other checkpoint inhibitors

5. Patients who had received radiation within 14 days prior to the first dose of study
drug

Other protocol-defined inclusion/exclusion criteria may apply
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Novartis Investigative Site - St Leonards
Recruitment postcode(s) [1] 0 0
2065 - St Leonards
Recruitment outside Australia
Country [1] 0 0
United Kingdom
State/province [1] 0 0
Surrey

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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 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.
Trial website
https://clinicaltrials.gov/show/NCT03176264
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03176264