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).
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
| Drug | Synonyms | Arms |
|---|
| CGM097 | | CGM097 - Dose Expansion at MTD or RP2D |
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
| Name | Type | Description | Interventions |
|---|
| CGM097 - Dose escalation | Experimental | | |
| CGM097 - Dose Expansion at MTD or RP2D | Experimental | | |
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: | Completed |
| Lead Sponsor: | Novartis Pharmaceuticals |
Trial Keywords
Last Updated
June 15, 2021
