A Phase I Dose Escalation Study of CGM097 in Adult Patients With Selected Advanced Solid Tumors (CCGM097X2101)

This study is currently recruiting participants.
Verified December 2013 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01760525
First received: January 2, 2013
Last updated: December 5, 2013
Last verified: December 2013
  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).


Condition Intervention Phase
Solid Tumor With p53 Wild Type Status
Drug: CGM097
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Incidence of Dose Limiting Toxicities [ Time Frame: From day 1 to day 28 of treatment ] [ Designated as safety issue: Yes ]
    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:
  • 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. ] [ Designated as safety issue: No ]
    Plasma concentration of CGM097

  • Tumor response per RECIST [ Time Frame: Baseline, then every third cycle (approximately every 12 weeks), until disease progression or discontinuation. ] [ Designated as safety issue: No ]
    This includes duration of response and progression free survival

  • Pharmacodynamic effect of CGM097 [ Time Frame: At baseline, Cycle 2 Day 8 and at disease progression. ] [ Designated as safety issue: No ]
    Changes of tumors markers in tumor tissue and blood

  • 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). ] [ Designated as safety issue: Yes ]
    Changes in laboratory values, vital signs or cardiac functionality, dose reduction, dose interruption and dose intensity, incidence and severity of adverse events.


Estimated Enrollment: 92
Study Start Date: March 2013
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CGM097 - Dose escalation Drug: CGM097
Patients treated with CGM097
Experimental: CGM097 - Dose Expansion at MTD or RP2D Drug: CGM097
Patients treated with CGM097

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01760525

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals

Locations
United States, Massachusetts
Dana Farber Cancer Institute SC (2) Not yet recruiting
Boston, Massachusetts, United States, 02115
Contact: Brian Beardslee    617-632-5638    bbeardslee1@partners.org   
Principal Investigator: George D. Demetri         
France
Novartis Investigative Site Recruiting
Lyon Cedex, France, 69373
Germany
Novartis Investigative Site Recruiting
Essen, Germany, 45147
Novartis Investigative Site Recruiting
Köln, Germany, 50924
Singapore
Novartis Investigative Site Recruiting
Singapore, Singapore, 169610
Switzerland
Novartis Investigative Site Recruiting
Zürich, Switzerland, 8091
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01760525     History of Changes
Other Study ID Numbers: CCGM097X2101, 2012-000940-87
Study First Received: January 2, 2013
Last Updated: December 5, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
p53, solid tumor

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on April 17, 2014