PDR001 in Combination With Bevacizumab and mFOLFOX6 as First Line Therapy in Patients With Metastatic MSS Colorectal Cancer

Metastatic Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03176264
• Other study ID #: CPDR001I2101
• Secondary ID: 2017-000520-96
• Status: Terminated
• Phase: Phase 1
• Start date: September 25, 2017
• Est. completion date: January 30, 2018

Study information

• Verified date: October 2021
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: January 30, 2018
• Est. primary completion date: January 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

Drug:
• PDR001
400 mg every 4 weeks
• bevacizumab
5 mg/kg every 2 weeks
• mFOLFOX6
Combination of chemotherapy administered every 2 weeks: oxaliplatin (85mg/m2), 5-Fluorouracil (2400mg/m2) and folinic acid (=leucovorin, 400mg/m2)

Locations

Country	Name	City	State
United Kingdom	Novartis Investigative Site	Sutton	Surrey

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United Kingdom, 

Outcome

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

External Links

•   A Plain Language Trial Summary is available on novartisclinicaltrials.com
•   Novartis results database