Solid Tumor With p53 Wild Type StatusPhase 1CCGM097X2101NCT01760525
A Phase I Dose Escalation Study of CGM097 in Adult Patients With Selected Advanced Solid Tumors
A Phase 1 study testing CGM097 in people with Solid Tumor With p53 Wild Type Status, run by Novartis Pharmaceuticals at 5 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumor With p53 Wild Type Status
- What is being tested?
- CGM097
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- 5 sitesin 5 countries
- Study dates
- 20 Mar 2013to 24 Jul 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
5 sites in 5 countries.
5 sites in 5 countries
United States1 site
Dana Farber Cancer Institute SC (2)
Boston, Massachusetts, 02215
About this study
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
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).
Read the 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.
- Conditions
- Solid Tumor With p53 Wild Type Status
- Being tested
- CGM097
- Keywords
- p53, solid tumor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CGM097Drug
Patients treated with CGM097
| Study group | Role | What they receive |
|---|---|---|
| CGM097 - Dose escalation | Experimental | Not described Receives: Drug: CGM097 |
| CGM097 - Dose Expansion at MTD or RP2D | Experimental | Not described Receives: Drug: CGM097 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Dose Limiting Toxicities
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
Measured: From day 1 to day 28 of treatment
Secondary outcomes (4)
Pharmacokinetic profile of CGM097
Plasma concentration of CGM097
Measured: At Cycle 1 Day 1, 2, 5, 8, 15 and 22, then each first day of the Cycle (28 days per Cycle) until discontinuation.
Tumor response per RECIST
This includes duration of response and progression free survival
Measured: Baseline, then every third cycle (approximately every 12 weeks), until disease progression or discontinuation.
Pharmacodynamic effect of CGM097
Changes of tumors markers in tumor tissue and blood
Measured: At baseline, Cycle 2 Day 8 and at disease progression.
Changes in laboratory values, vital signs or cardiac functionality, dose reduction, dose interruption and dose intensity, incidence and severity of adverse events.
Changes in laboratory values, vital signs or cardiac functionality, dose reduction, dose interruption and dose intensity, incidence and severity of adverse events.
Measured: 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).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jan 2013 (estimated)
- Study start20 Mar 2013
- Primary completion24 Jul 2020
- Study completion24 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Solid Tumor With p53 Wild Type StatusStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01760525
- Sponsor's protocol ID
- CCGM097X2101
- Other IDs
- 2012-000940-87
- Acronym
- CCGM097X2101
- Status last verified
- Jun 2021
- First submitted
- 2 Jan 2013
- Last updated
- 15 Jun 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Bauer S, Demetri GD, Halilovic E, Dummer R, Meille C, Tan DSW, Guerreiro N, Jullion A, Ferretti S, Jeay S, Van Bree L, Hourcade-Potelleret F, Wuerthner JU, Fabre C, Cassier PA. Pharmacokinetic-pharmacodynamic guided optimisation of dose and schedule of CGM097, an HDM2 inhibitor, in preclinical and clinical studies. Br J Cancer. 2021 Aug;125(5):687-698. doi: 10.1038/s41416-021-01444-4. Epub 2021 Jun 17.
PubMed 34140638
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01760525
- Acronym / sponsor ID
- CCGM097X2101 / CCGM097X2101
- Conditions
- Solid Tumor With p53 Wild Type Status
- Keywords
- p53, solid tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 20 Mar 2013 (actual)
- Primary completion
- 24 Jul 2020 (actual)
- Study completion
- 24 Jul 2020 (actual)
- First posted
- 4 Jan 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CGM097 - Dose escalation | Experimental | Drug: CGM097 |
| CGM097 - Dose Expansion at MTD or RP2D | Experimental | Drug: CGM097 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CGM097Patients treated with CGM097 | Drug | CGM097 - Dose Expansion at MTD or RP2D, CGM097 - Dose escalation |
Primary outcome
Incidence of Dose Limiting Toxicities
Time frame: 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
4 secondary outcomes
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.
Tumor response per RECIST
Time frame: Baseline, then every third cycle (approximately every 12 weeks), until disease progression or discontinuation.
Pharmacodynamic effect of CGM097
Time frame: At baseline, Cycle 2 Day 8 and at disease progression.
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).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2021.
- Derived from this study: PubMed 34140638Bauer S, Demetri GD, Halilovic E, Dummer R, Meille C, Tan DSW, Guerreiro N, Jullion A, Ferretti S, Jeay S, Van Bree L, Hourcade-Potelleret F, Wuerthner JU, Fabre C, Cassier PA. Pharmacokinetic-pharmacodynamic guided optimisation of dose and schedule of CGM097, an HDM2 inhibitor, in preclinical and clinical studies. Br J Cancer. 2021 Aug;125(5):687-698. doi: 10.1038/s41416-021-01444-4. Epub 2021 Jun 17.
- Study ResultsLink provided by the sponsor.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
5 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CGM097 in people with Solid Tumor With p53 Wild Type Status, run by Novartis Pharmaceuticals at 5 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States, France, Germany, Singapore, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Dose Limiting Toxicities (time frame: From day 1 to day 28 of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01760525, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2021.