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Study of CB-103 in Adult Patients With Advanced or Metastatic Solid Tumours and Haematological Malignancies

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03422679
Recruitment Status : Recruiting
First Posted : February 6, 2018
Last Update Posted : January 21, 2022
Sponsor:
Information provided by (Responsible Party):
Cellestia Biotech AG

Brief 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.

Condition or disease Intervention/treatment Phase
Breast Cancer Colorectal Cancer Adenoid Cystic Carcinoma Non-hodgkin Lymphoma Glomus Tumor, Malignant Hepatocellular Carcinoma Osteosarcoma T-ALL Drug: CB-103 Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : December 5, 2017
Estimated Primary Completion Date : October 31, 2022
Estimated Study Completion Date : December 31, 2022


Arm Intervention/treatment
Experimental: CB-103
CB-103 capsules will be administered orally in treatment cycles of 28-days each.
Drug: CB-103
Hard gelatine capsules taken orally during treatment period. Treatment cycle is 28 days.




Primary Outcome Measures :
  1. Part A: Dose limiting toxicity (DLT) [ Time Frame: 28 days ]
    Number of patients with dose limiting toxicity

  2. Part B: antitumour efficacy [ Time Frame: up to 12 months ]
    Best overall response rates of each tumor type using appropriate response Evaluation Criteria


Secondary Outcome Measures :
  1. Part A and B: incidence of all adverse events and serious adverse events (safety and tolerability) [ Time Frame: up to 12 months ]
    Number of participants with adverse events as a measure of safety and tolerability

  2. Part A and B: pharmacokinetic - Cmax [ Time Frame: PK profiling in cycle 1 and 2 (cycle duration: 28 days) ]
    Maximum plasma concentration

  3. Part A and B: pharmacokinetic - tmax [ Time Frame: PK profiling in cycle 1 and 2 (cycle duration: 28 days) ]
    Time to Cmax

  4. Part A and B: pharmacokinetic - AUC [ Time Frame: PK profiling in cycle 1 and 2 (cycle duration: 28 days) ]
    Area under the curve during 8 and 24 hours

  5. Part A and B: pharmacokinetic - t1/2 [ Time Frame: PK profiling in cycle 1 and 2 (cycle duration: 28 days) ]
    elimination half-life

  6. Part A: preliminary antitumour efficacy [ Time Frame: up to 6 months ]
    Overall response rates of each tumor type using appropriate response evaluation criteria



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA:

  1. 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.
  2. Demography: men and women ≥ 18 years old
  3. Adequate organ function and laboratory results
  4. Adequate contraceptive measures
  5. Signed informed consent

EXCLUSION CRITERIA

  1. Medical History

    1. Patients with symptomatic CNS metastases (neurologically unstable or requiring increasing doses of steroids to control their CNS disease)
    2. Hypersensitivity to any of the excipients of CB-103
    3. Patients with unresolved nausea, vomiting, or diarrhoea of CTCAE grade > 1
    4. Impairment of GI function or presence of GI disease that may significantly alter the absorption of CB-103
    5. History of second or other primary cancer with the exception of:

      • 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.
  2. Exclusionary concurrent medical conditions Impaired cardiac function or clinically significant cardiac diseases.
  3. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03422679


Contacts
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Contact: Florian Vogl, MD, PhD +41 61 6332957 florian.vogl@cellestia.com

Locations
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Sponsors and Collaborators
Cellestia Biotech AG
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Responsible Party: Cellestia Biotech AG
ClinicalTrials.gov Identifier: NCT03422679    
Other Study ID Numbers: CB103-C-101
First Posted: February 6, 2018    Key Record Dates
Last Update Posted: January 21, 2022
Last Verified: January 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Cellestia Biotech AG:
advanced solid tumours
haematological malignancies
phase I/II
NOTCH pathway
pan-NOTCH inhibitor
Additional relevant MeSH terms:
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Carcinoma
Neoplasms
Osteosarcoma
Carcinoma, Adenoid Cystic
Hematologic Neoplasms
Glomus Tumor
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms by Site
Adenocarcinoma
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Sarcoma
Hematologic Diseases
Neoplasms, Vascular Tissue