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A Phase I Dose Escalation Study of CGM097 in Adult Patients With Selected Advanced Solid Tumors

NCT01760525

Description:

This is a first in human phase I study of single agent CGM097 in patients with advanced solid tumors who have progressed despite standard therapy or for whom no standard therapy exists. The tumor must be characterized by p53wt status. The study consists of a dose escalation part where patients will receive escalating doses of CGM097, and a dose expansion part in which patients are given CGM097 at the maximum tolerated dose (MTD) or Recommended Phase 2 Dose (RP2D). Each dose escalation step will be decided based on the recommendation from an adaptive Bayesian logistic regression model (BLRM).

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Phase I Dose Escalation Study of CGM097 in Adult Patients With Selected Advanced Solid Tumors
  • Official Title: A Phase I, Open-label, Multi-center, Dose Escalation Study of Oral CGM097, a p53/HDM2-interaction Inhibitor, in Adult Patients With Selected Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: CCGM097X2101
  • SECONDARY ID: 2012-000940-87
  • NCT ID: NCT01760525

Conditions

  • Solid Tumor With p53 Wild Type Status

Interventions

DrugSynonymsArms
CGM097CGM097 - Dose escalation

Purpose

This is a first in human phase I study of single agent CGM097 in patients with advanced solid tumors who have progressed despite standard therapy or for whom no standard therapy exists. The tumor must be characterized by p53wt status. The study consists of a dose escalation part where patients will receive escalating doses of CGM097, and a dose expansion part in which patients are given CGM097 at the maximum tolerated dose (MTD) or Recommended Phase 2 Dose (RP2D). Each dose escalation step will be decided based on the recommendation from an adaptive Bayesian logistic regression model (BLRM).

Detailed Description

      This is a multi-center, open-label, dose finding, phase I study of single agent CGM097,
      administered in patients with advanced solid tumors who have progressed despite standard
      therapy or for whom no standard therapy exists. Patients' tumors must be characterized by
      p53wt status.

      The study consists of a dose escalation part, where cohorts of three to six newly enrolled
      patients will receive escalating doses of CGM097, and a dose expansion part, in which
      patients are given CGM097 the maximum tolerated dose (MTD) or Recommended Phase 2 Dose
      (RP2D). Novartis and the site investigators will jointly decide on each dose escalation step
      based on the recommendation from an adaptive Bayesian logistic regression model (BLRM). If
      safety data should indicate a lower increment than suggested by the BLRM, the next dose level
      (DL) will be adjusted accordingly.
    

Trial Arms

NameTypeDescriptionInterventions
CGM097 - Dose escalationExperimental
  • CGM097
CGM097 - Dose Expansion at MTD or RP2DExperimental
  • CGM097

Eligibility Criteria

        Inclusion Criteria:

          -  Patient has advanced solid malignancy that has progressed despite standard therapy, or
             for which no effective standard therapy exists

          -  Tumor of the patient is p53wt

          -  Evaluable disease as determined by RECIST 1.1

          -  WHO performance status 0-2

        Exclusion criteria:

          -  Prior treatment with CGM097 or other p53/HDM2-interaction inhibitor

          -  Patient with symptomatic or growing CNS metastatic lesions

          -  Concurrent other malignancy

          -  Clinically significant cardiac disease as defined in the protocol

          -  Diagnosis of acute or chronic pancreatitis

          -  Concomitant therapy that precludes enrollment, as defined in the protocol

          -  Women of child-bearing potential, unless they are using highly effective methods of
             contraception during dosing and for 2 weeks after study drug discontinuation

          -  Pregnant or nursing women

        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 Toxicities
Time Frame:From day 1 to day 28 of treatment
Safety Issue:
Description:To characterize the maximum tolerated dose (MTD) and/or identify the recommended dose for expansion(RDE) of CGM097. Dose Limiting Toxicities will be listed and their incidence summarized by primary system organ class, worst grade based on CTCAE version 4.03 and type of Adverse Event

Secondary Outcome Measures

Measure:Pharmacokinetic profile of CGM097
Time Frame:At Cycle 1 Day 1, 2, 5, 8, 15 and 22, then each first day of the Cycle (28 days per Cycle) until discontinuation.
Safety Issue:
Description:Plasma concentration of CGM097
Measure:Tumor response per RECIST
Time Frame:Baseline, then every third cycle (approximately every 12 weeks), until disease progression or discontinuation.
Safety Issue:
Description:This includes duration of response and progression free survival
Measure:Pharmacodynamic effect of CGM097
Time Frame:At baseline, Cycle 2 Day 8 and at disease progression.
Safety Issue:
Description:Changes of tumors markers in tumor tissue and blood
Measure:Changes in laboratory values, vital signs or cardiac functionality, dose reduction, dose interruption and dose intensity, incidence and severity of adverse events.
Time Frame:At Cycle 1 Day 1, 2, 5, 8, 15, 22 and 28, Cycle 2 Day 1, 8,15 and 22, then each Day 1 and 15 of the Cycle until discontinuation. For dose interruption, dose intensity and adverse events: each day of the Cycle until discontinuation (28 days per Cycle).
Safety Issue:
Description:Changes in laboratory values, vital signs or cardiac functionality, dose reduction, dose interruption and dose intensity, incidence and severity of adverse events.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • p53, solid tumor

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