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

Sponsor

Cellestia Biotech AG (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03422679

Collaborator

(none)

200

Enrollment

Locations

Arm

60.8

Anticipated Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Study Design

Study Type:

Interventional

Anticipated 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 :

Dec 5, 2017

Anticipated Primary Completion Date :

Oct 31, 2022

Anticipated Study Completion Date :

Dec 31, 2022

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Part A: Dose limiting toxicity (DLT) [28 days]
Number of patients with dose limiting toxicity
Part B: antitumour efficacy [up to 12 months]
Best overall response rates of each tumor type using appropriate response Evaluation Criteria

Secondary Outcome Measures

Part A and B: incidence of all adverse events and serious adverse events (safety and tolerability) [up to 12 months]
Number of participants with adverse events as a measure of safety and tolerability
Part A and B: pharmacokinetic - Cmax [PK profiling in cycle 1 and 2 (cycle duration: 28 days)]
Maximum plasma concentration
Part A and B: pharmacokinetic - tmax [PK profiling in cycle 1 and 2 (cycle duration: 28 days)]
Time to Cmax
Part A and B: pharmacokinetic - AUC [PK profiling in cycle 1 and 2 (cycle duration: 28 days)]
Area under the curve during 8 and 24 hours
Part A and B: pharmacokinetic - t1/2 [PK profiling in cycle 1 and 2 (cycle duration: 28 days)]
elimination half-life
Part A: preliminary antitumour efficacy [up to 6 months]
Overall response rates of each tumor type using appropriate response evaluation criteria

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

INCLUSION CRITERIA:

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

EXCLUSION CRITERIA

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:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sarcoma Oncology Research Center	Santa Monica	California	United States	90403
2	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
3	MD Anderson	Houston	Texas	United States	77030
4	Centre Hospitalier Lyon-Sud	Lyon		France
5	Hôpital Saint-Louis	Paris		France	75475
6	Charite- Universitaetsmedizin Berlin- Campus Benjamin Franklin	Berlin		Germany	10117
7	Universitätsklinikum Frankfurt	Frankfurt		Germany	60590
8	Nationales Centrum für Tumorerkrankungen Heidelberg	Heidelberg		Germany	69120
9	Seoul National University Hospital	Seoul		Korea, Republic of	03080
10	Severance Hospital - Yonsei Cancer Center	Seoul		Korea, Republic of	03722
11	Seoul National University Hospital	Seoul		Korea, Republic of	06351
12	Academic Medical Center	Amsterdam		Netherlands	1105 AZ
13	Maastricht UMC	Maastricht		Netherlands	6202 AZ
14	UMC Utrecht Cancer Center	Utrecht		Netherlands	3508 GA
15	Hospital Quirón Barcelona	Barcelona		Spain	08023
16	Vall d'Hebron Institute of Oncology (VHIO)	Barcelona		Spain	08035
17	Catalan Institute of Oncology	Barcelona		Spain	08916
18	Hospital Ramón y Cajal	Madrid		Spain	28034
19	Oncology Institute of Southern Switzerland	Bellinzona		Switzerland	6500
20	Kantonsspital St.Gallen	Saint Gallen		Switzerland	9007