Breast CancerPhase 1/2NCT03422679
Study of CB-103 in Adult Patients With Advanced or Metastatic Solid Tumours and Haematological Malignancies
A Phase 1/2 study testing CB-103 in people with Breast Cancer and Colorectal Cancer, run by Cellestia Biotech AG at 17 sites in 6 countries.
Trial summary
This is a phase I/II, non randomized, open-label, dose escalation study to investigate the safety, tolerability and preliminary efficacy of CB-103. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, Colorectal Cancer, Adenoid Cystic Carcinoma
- What is being tested?
- CB-103
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 79 participants
- Where
- 17 sitesin 6 countries
- Study dates
- 5 Dec 2017to 11 Nov 2022
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Disease
- Patients with histologically or cytologically confirmed solid tumours (breast cancer (triple negative breast cancer [TNBC], ER+/-, HER2+/-), gastrointestinal (GI) cancers (resistant to oxaliplatin or irinotecan-based therapy colorectal cancer [CRC]), osteosarcoma, adenoid cystic carcinoma (ACC), and malignant glomus tumour) that are surgically unresectable, locally advanced, or metastatic and whose disease has progressed on at least one line of systemic therapy (with the exception of ACC patients who are allowed to be systemic treatment-naïve) and for whom no established therapeutic alternatives exist. Any other solid cancer (including lymphoma) with a confirmed NOTCH1-4 activating mutation or genetic lesion.
- Relapsed or refractory (r/r) T-cell acute lymphoblastic leukaemia (T-ALL) or lymphoma (T-LBL) with a confirmed NOTCH pathway activation. Refractory patients are defined as T-ALL/T-LBL patients with ≥ 5% bone marrow blasts, and/or concomitant extramedullary involvement, who have not achieved a CR after standard induction/consolidation therapy attempt.
- Demography: men and women ≥ 18 years old
- Adequate organ function and laboratory results
- Adequate contraceptive measures
- Signed informed consent
Who cannot join
- Medical History
- Patients with symptomatic CNS metastases (neurologically unstable or requiring increasing doses of steroids to control their CNS disease)
- Hypersensitivity to any of the excipients of CB-103
- Patients with unresolved nausea, vomiting, or diarrhoea of CTCAE grade > 1
- Impairment of GI function or presence of GI disease that may significantly alter the absorption of CB-103
- History of second or other primary cancer with the exception of:
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- Curatively treated non-melanomatous skin cancer
- Curatively treated cervical cancer or breast carcinoma in situ
- Other primary solid tumour treated with curative intent and no known active disease present and no treatment administered during the last 2 years.
- Exclusionary concurrent medical conditions Impaired cardiac function or clinically significant cardiac diseases.
- Prior Therapy
- In patients with solid tumours cytotoxic chemotherapy within 3 weeks
- In T-ALL/T-LBL patients, prior anticancer therapy less than 2 weeks prior to starting therapy or 5 half-lives (whichever is longer) with exceptions.
- Radiation therapy within 2 weeks of scheduled CB-103 dosing day 1
- Immunotherapy, biological therapies, targeted small molecules, hormonal therapies within 3 weeks of scheduled CB-103 dosing day 1
- Unresolved toxicity CTCAE grade > 1 from previous anti-cancer therapy or radiotherapy (excluding neurotoxicity, alopecia, ototoxicity, lymphopenia), or incomplete recovery from previous surgery.
Trial locations and contacts
17 sites in 6 countries.
17 sites in 6 countries
Spain4 sites
Hospital Quirón Barcelona
Barcelona, 08023
Vall d'Hebron Institute of Oncology (VHIO)
Barcelona, 08035
Catalan Institute of Oncology
Barcelona, 08916
Hospital Ramón y Cajal
Madrid, 28034
United States3 sites
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
MD Anderson
Houston, Texas, 77030
Sarcoma Oncology Research Center
Santa Monica, California, 90403
Germany3 sites
Charite- Universitaetsmedizin Berlin- Campus Benjamin Franklin
Berlin, 10117
Universitätsklinikum Frankfurt
Frankfurt, 60590
Nationales Centrum für Tumorerkrankungen Heidelberg
Heidelberg, 69120
South Korea3 sites
Seoul National University Hospital
Seoul, 03080
Severance Hospital - Yonsei Cancer Center
Seoul, 03722
Seoul National University Hospital
Seoul, 06351
Switzerland2 sites
Oncology Institute of Southern Switzerland
Bellinzona, 6500
Kantonsspital St.Gallen
Sankt Gallen, 9007
About this study
Official title: A Phase I/IIA, Multi-Centre, Open-Label, Dose-Escalation Study With Expansion Arms to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of CB-103 Administered Orally in Adult Patients With Locally Advanced or Metastatic Solid Tumours and Haematological Malignancies Characterised by Alterations of the NOTCH Signalling Pathway
This is a phase I/II, non randomized, open-label, dose escalation study to investigate the safety, tolerability and preliminary efficacy of CB-103.
Read the detailed description
This Phase I/IIA, open label, multicenter, dose escalation study of CB-103 in patients with Locally Advanced or Metastatic Solid Tumours and Haematological Malignancies. After providing signed informed consent, patients will be screened for entry into the study. The study will be conducted in 2 stages: dose escalation in Part A of the study (Phase I) followed by dose expansion in Part B (Phase IIA).
Escalation cohorts will receive repeat doses of CB-103 to determine the MTD and RP2D.
CB-103 will be administered orally in treatment cycles of 28-days each. Aim of the expansion Phase IIA, Part B of the study will be to collect preliminary evidence of anti-tumour activity.
- Conditions
- Breast Cancer, Colorectal Cancer, Adenoid Cystic Carcinoma, Non-hodgkin Lymphoma, Glomus Tumor, Malignant, Hepatocellular Carcinoma
- Being tested
- CB-103
- Keywords
- advanced solid tumours, haematological malignancies, phase I/II, NOTCH pathway, pan-NOTCH inhibitor
- Medical subject headings
- Breast Neoplasms, Colorectal Neoplasms, Carcinoma, Adenoid Cystic, Lymphoma, Non-Hodgkin, Glomus Tumor, Carcinoma, Hepatocellular, Osteosarcoma, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CB-103Drug
Hard gelatine capsules taken orally during treatment period. Treatment cycle is 28 days.
| Study group | Role | What they receive |
|---|---|---|
| CB-103 | Experimental | CB-103 capsules will be administered orally in treatment cycles of 28-days each. Receives: Drug: CB-103 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Limiting Toxicity (DLT)
Number of patients with dose limiting toxicity during the first cycle.
DLT is defined as a severe adverse event or abnormal laboratory value assessed as unrelated to disease progression, inter-current illness, or concomitant medications, that occurs ≤ 28 days following the first dose of CB-103 (Cycle 1).
Measured: 28 days
Secondary outcomes (1)
Overall Response Rate
Number of patients with an overall response rate (CR+PR assessed by RECSIT v1.1 or CR or CRi by NCCN guidelines) up to 24 months
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2018
- Study start5 Dec 2017
- Primary completion11 Nov 2022
- Study completion11 Nov 2022
Why it stopped: business reason
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 79 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cellestia Biotech AG
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Elena Garalda, MD, PhD, Principal investigator, Vall d'Hebron University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03422679
- Sponsor's protocol ID
- CB103-C-101
- Status last verified
- Jan 2024
- First submitted
- 19 Jan 2018
- Last updated
- 16 Jan 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Hanna GJ, Stathis A, Lopez-Miranda E, Racca F, Quon D, Leyvraz S, Hess D, Keam B, Rodon J, Ahn MJ, Kim HR, Schneeweiss A, Ribera JM, DeAngelo D, Perez Garcia JM, Cortes J, Schonborn-Kellenberger O, Weber D, Pisa P, Bauer M, Beni L, Bobadilla M, Lehal R, Vigolo M, Vogl FD, Garralda E. A Phase I Study of the Pan-Notch Inhibitor CB-103 for Patients with Advanced Adenoid Cystic Carcinoma and Other Tumors. Cancer Res Commun. 2023 Sep 14;3(9):1853-1861. doi: 10.1158/2767-9764.CRC-23-0333.
PubMed 37712875Alfaifi A, Bahashwan S, Alsaadi M, Ageel AH, Ahmed HH, Fatima K, Malhan H, Qadri I, Almehdar H. Advancements in B-Cell Non-Hodgkin's Lymphoma: From Signaling Pathways to Targeted Therapies. Adv Hematol. 2024 Nov 12;2024:5948170. doi: 10.1155/2024/5948170. eCollection 2024.
PubMed 39563886
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/IIA, Multi-Centre, Open-Label, Dose-Escalation Study With Expansion Arms to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of CB-103 Administered Orally in Adult Patients With Locally Advanced or Metastatic Solid Tumours and Haematological Malignancies Characterised by Alterations of the NOTCH Signalling Pathway
- ClinicalTrials.gov ID
- NCT03422679
- Acronym / sponsor ID
- CB103-C-101
- Conditions
- Breast Cancer, Colorectal Cancer, Adenoid Cystic Carcinoma, Non-hodgkin Lymphoma, Glomus Tumor, Malignant, Hepatocellular Carcinoma
- Keywords
- advanced solid tumours, haematological malignancies, phase I/II, NOTCH pathway, pan-NOTCH inhibitor
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: business reason
- Enrolment
- 79 participants (actual)
- Lead sponsor
- Cellestia Biotech AGIndustry (pharma, biotech, devices)
- Study start
- 5 Dec 2017 (actual)
- Primary completion
- 11 Nov 2022 (actual)
- Study completion
- 11 Nov 2022 (actual)
- First posted
- 6 Feb 2018 (actual)
- Results
- Posted 16 Jan 2024
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 phase I/II, non randomized, open-label, dose escalation study to investigate the safety, tolerability and preliminary efficacy of CB-103.
Detailed description
This Phase I/IIA, open label, multicenter, dose escalation study of CB-103 in patients with Locally Advanced or Metastatic Solid Tumours and Haematological Malignancies. After providing signed informed consent, patients will be screened for entry into the study. The study will be conducted in 2 stages: dose escalation in Part A of the study (Phase I) followed by dose expansion in Part B (Phase IIA).
Escalation cohorts will receive repeat doses of CB-103 to determine the MTD and RP2D.
CB-103 will be administered orally in treatment cycles of 28-days each. Aim of the expansion Phase IIA, Part B of the study will be to collect preliminary evidence of anti-tumour activity.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CB-103 | Experimental | Drug: CB-103CB-103 capsules will be administered orally in treatment cycles of 28-days each. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Disease
- Demography: men and women ≥ 18 years old
- Adequate organ function and laboratory results
- Adequate contraceptive measures
- Signed informed consent
Key exclusion criteria (16 listed)
- Medical History
- Exclusionary concurrent medical conditions Impaired cardiac function or clinically significant cardiac diseases.
- Prior Therapy
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 |
|---|---|---|
| CB-103Hard gelatine capsules taken orally during treatment period. Treatment cycle is 28 days. | Drug | CB-103 |
Primary outcome
Dose Limiting Toxicity (DLT)
Time frame: 28 days
Number of patients with dose limiting toxicity during the first cycle. DLT is defined as a severe adverse event or abnormal laboratory value assessed as unrelated to disease progression, inter-current illness, or concomitant medications, that occurs ≤ 28 days following the first dose of CB-103 (Cycle 1).
1 secondary outcome
Overall Response Rate
Time frame: 24 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jan 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 37712875Hanna GJ, Stathis A, Lopez-Miranda E, Racca F, Quon D, Leyvraz S, Hess D, Keam B, Rodon J, Ahn MJ, Kim HR, Schneeweiss A, Ribera JM, DeAngelo D, Perez Garcia JM, Cortes J, Schonborn-Kellenberger O, Weber D, Pisa P, Bauer M, Beni L, Bobadilla M, Lehal R, Vigolo M, Vogl FD, Garralda E. A Phase I Study of the Pan-Notch Inhibitor CB-103 for Patients with Advanced Adenoid Cystic Carcinoma and Other Tumors. Cancer Res Commun. 2023 Sep 14;3(9):1853-1861. doi: 10.1158/2767-9764.CRC-23-0333.
- Derived from this study: PubMed 39563886Alfaifi A, Bahashwan S, Alsaadi M, Ageel AH, Ahmed HH, Fatima K, Malhan H, Qadri I, Almehdar H. Advancements in B-Cell Non-Hodgkin's Lymphoma: From Signaling Pathways to Targeted Therapies. Adv Hematol. 2024 Nov 12;2024:5948170. doi: 10.1155/2024/5948170. eCollection 2024.
- Individual participant dataSharing planned: No
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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.
Elena Garalda, MD, PhD principal investigator
Vall d'Hebron University Hospital
17 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing CB-103 in people with Breast Cancer and Colorectal Cancer, run by Cellestia Biotech AG at 17 sites in 6 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 7 inclusion and 16 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: stopped early, as of the sponsor's last update on 16 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in Spain, United States, Germany, South Korea, France and 1 more country. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Jan 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Dose Limiting Toxicity (DLT) (time frame: 28 days). 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 NCT03422679, which also lists 2 linked publications.
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 16 Jan 2024.