Clinical Trials /

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

NCT03176264

Description:

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.

Related Conditions:
  • Colorectal Adenocarcinoma
Recruiting Status:

Terminated

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: PDR001 in Combination With Bevacizumab and mFOLFOX6 as First Line Therapy in Patients With Metastatic MSS Colorectal Cancer
  • 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 IDs

  • ORG STUDY ID: CPDR001I2101
  • SECONDARY ID: 2017-000520-96
  • NCT ID: NCT03176264

Conditions

  • Metastatic Colorectal Cancer

Interventions

DrugSynonymsArms
PDR001PDR001
bevacizumabPDR001
mFOLFOX6PDR001

Purpose

This is 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 will assess primarily the safety and tolerability and then the efficacy of PDR001 in combination with bevacizumab and mFOLFOX6. Particular attention will be paid to the level of activity of study drug combinations in CMS4 patients (retrospective analysis).

Trial Arms

NameTypeDescriptionInterventions
PDR001Experimental
  • PDR001
  • bevacizumab
  • mFOLFOX6

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Dose-limiting toxicity (DLT)
Time Frame:12 months
Safety Issue:
Description:RECIST v1.1 = Response Evaluation Criteria in Solid Tumors v1.1

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:
Measure:Overall survival (OS)
Time Frame:Every 3 months after last visit up to 1 year after last patient last visit
Safety Issue:
Description:
Measure:Progression free survival
Time Frame:Baseline, every 8 weeks until progression per central assessment up to 1 year after last patient last visit
Safety Issue:
Description:
Measure:Duration of response (DOR)
Time Frame:Baseline, every 8 weeks until progression per central assessment up to 1 year after last patient last visit
Safety Issue:
Description:
Measure:Disease control rate (DCR)
Time Frame:Baseline, every 8 weeks until progression per central assessment up to 1 year after last patient last visit
Safety Issue:
Description:
Measure:Time to response (TTR)
Time Frame:Baseline, every 8 weeks until progression per central assessment up to 1 year after last patient last visit
Safety Issue:
Description:
Measure:Ctrough
Time Frame:Through end of treatment completion, an average of 14 months
Safety Issue:
Description:
Measure:Cmax
Time Frame:Through end of treatment completion, an average of 14 months
Safety Issue:
Description:
Measure:Area under the curve (AUC)
Time Frame:Through end of treatment completion, an average of 14 months
Safety Issue:
Description:
Measure:Antidrug antibodies (ADA)
Time Frame:Through end of treatment completion, an average of 14 months
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • PDR001
  • immunotherapy
  • bevacizumab
  • mFOLFOX6
  • CRC
  • MMS
  • CMS4
  • ElevatION;CRC-101

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