Solid Tumor With p53 Wild Type Status
Conditions
Keywords
p53, solid tumor
Brief summary
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.
Interventions
DRUGCGM097
Patients treated with CGM097
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Dose Limiting Toxicities | From day 1 to day 28 of treatment | 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
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic profile of CGM097 | At Cycle 1 Day 1, 2, 5, 8, 15 and 22, then each first day of the Cycle (28 days per Cycle) until discontinuation. | Plasma concentration of CGM097 |
| Tumor response per RECIST | Baseline, then every third cycle (approximately every 12 weeks), until disease progression or discontinuation. | This includes duration of response and progression free survival |
| Pharmacodynamic effect of CGM097 | At baseline, Cycle 2 Day 8 and at disease progression. | 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. | 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). | Changes in laboratory values, vital signs or cardiac functionality, dose reduction, dose interruption and dose intensity, incidence and severity of adverse events. |
Countries
France, Germany, Singapore, Switzerland, United States
Outcome results
None listed