This study has been transitioned to CTIS with ID 2023-506794-35-00 check the CTIS register for the current data. - Primary Objective:To evaluate the safety and tolerability of investigational regimens of sotorasib in adult subjects with KRAS p.G12C…
ID
Source
Brief title
Condition
- Other condition
- Malignant and unspecified neoplasms gastrointestinal NEC
Synonym
Health condition
colorectaal kanker / pancreas kanker
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Dose-limiting toxicities, treatment-emergent adverse events, treatment related
adverse events, and clinically significant changes in vital signs,
electrocardiograms (ECGs), and clinical laboratory tests
The primary analysis for this study will occur when target enrollment is
complete and each subject either completes at least 6 months on study or
withdraws from the study.
The final analysis will be conducted and reported following the end of the
study. The end of study date is defined as the date when the last subject
across all sites is assessed or receives an intervention for evaluation in the
study (ie, last subject last visit), including any additional parts in the
study (eg, long*term follow*up), as applicable.
Secondary outcome
Pharmacokinetic parameters of product(s) including, but not limited to, maximum
plasma concentration (Cmax), time to maximum plasma concentration (tmax), and
area under the plasma concentration-time curve (AUC)
Objective response rate (complete response [CR] + partial response [PR]),
disease control rate (DCR), duration of response (DOR), and progression-free
survival (PFS), measured by computed tomography (CT) or magnetic resonance
imaging (MRI) and assessed per Response Evaluation Criteria in Solid Tumors
Version 1.1 (RECIST 1.1).
The primary analysis for this study will occur when target enrollment is
complete and each subject either completes at least 6 months on study or
withdraws from the study. The final analysis will be conducted and reported
following the end of the study. The end of study date is defined as the date
when the last subject across all sites is assessed or receives an intervention
for evaluation in the study (ie, last subject last visit), including any
additional parts in the study (eg, long*term follow*up), as applicable.
Background summary
The rat sarcoma (RAS) proto-oncogene has been identified as an oncogenic driver
of tumour growth in both non small-cell lung cancer (NSCLC) and colorectal
cancer (CRC). Of the genes in the RAS family the KRAS is known to be the most
frequently mutated in most cancers.
The KRAS mutation occurs in approx. 13% of lung carcinoma and less than 5% of
other solid tumour cancers.
There have been many therapies developed in recent years but because the KRAS
mutation is hard to target there is a need to not only develop targeted
treatments for those presenting with this muation in their cancer but also to
identify these patients to be able to develop targeted therapies.
Sotorasib is a small molecule that irreversibly inhibits the KRAS G12C
mutation. It binds with other cells in the cancer tumour and stops cell growth
in the cells that harbour KRAS p.G12C mutations. Data collected so far suggests
therapeutic benefit to patients with KRAS p.G12C driven cancers. As well as the
anti-cancer activity Sotorasib is recorded as being safe and well-tolerated in
research studies to date, is being investigated as a first-line treatment
option to treat those patients with NSCLC KRAS p.G12C mutation.
Recent developments in the design of drug trials are becoming difficult to
capture in a traditional protocol design. Due to this Amgen considers this
study, 20190135, a master protocol using the platform design; study multiple
targeted therapies in the context of a single disease in a perpetual manner
with therapies allowed to enter or leave based on a decision algorithm. Suing
this approach Amgen hope to identify the most promising regime of Sotorasib for
further clinical research in an efficient and expedited manner.
Study objective
This study has been transitioned to CTIS with ID 2023-506794-35-00 check the CTIS register for the current data.
- Primary Objective:
To evaluate the safety and tolerability of investigational regimens of
sotorasib in adult subjects with KRAS p.G12C mutant advanced solid tumors
- Secondary Objectives:
To characterize PK of product(s) used in investigational regimens of sotorasib
in adult subjects with KRAS p.G12C mutant advanced solid tumors.
To evaluate anti-tumor activity of investigational regimens of sotorasib in
adult subjects with KRAS p.G12C mutant advanced solid tumors
Study design
This study (Subprotocol H) is part of CodeBreaK 101 Master protocol study
evaluating various sotorasib investigational regimens in advanced solid tumors
with KRAS p.G12C mutation. The Master protocol consists of individual
subprotocols that describe the details of the specific sotorasib
investigational regimen being evaluated. Subjects will be assigned for
screening in a non-randomized fashion to the individual subprotocols based
on investigator*s discretion. There is no overarching comparator arm within the
master protocol. Each of the individual subprotocols describe the design
elements associated with the evaluation of the specific sotorasib
investigational regimen(s).
See section on "aanvullende opmerkingen" in this ABR-form for the applicable
cohorts for the Netherlands.
Intervention
AMG 510 (sotorasib) in combination with other medication / therapy:
- Panitumumab
- Panitumumab plus FOLFIRI
- Panitumumab plus FOLFOX
Study burden and risks
Please refer to section E2 and E9.
Minervum 7061
Breda 4817 ZK
NL
Minervum 7061
Breda 4817 ZK
NL
Listed location countries
Age
Inclusion criteria
For the full list of inclusion criteria please refer to section 5.1 of the
subprotocols.
All subprotocols:
• Pathologically documented, metastatic colorectal cancer / metastatic
pancreatic cancer with KRAS p.G12C mutation identified through molecular
testing. KRAS p.G12C mutation must be identified by an approved diagnostic
device for detection of KRAS p.G12C in NSCLC or be performed in a Clinical
Laboratory Improvement Amendments (CLIA)-certified laboratory.
• Measurable disease per RECIST 1.1 criteria (Section 11.8)
• Eastern Cooperative Oncology Group (ECOG) Performance Status of <= 2
• Life expectancy of > 3 months, in the opinion of the investigator
• Ability to take oral medications and willing to record daily adherence to
investigational product
• Corrected QT interval (QTc) <= 470 msec for women and <= 450 msec for men
(based on average of screening triplicates
• Adequate hematological laboratory assessments, as follows:
- Absolute neutrophil count (ANC) >= 1.5 x 109/L
- Platelet count >= 100 x 109/L
- Hemoglobin >= 9 g/dL
• Adequate renal laboratory assessments, as follows:
- Estimated glomerular filtration rate based on Modification of Diet in Renal
Disease (MDRD) calculation >= 60 ml/min/1.73 m2
Exclusion criteria
For the full list of exclusion criteria please refer to section 5.2 of the
subprotocols.
All sub protocols
• History or presence of hematological malignancies unless curatively treated
with no evidence of disease >= 2 years
History of other malignancy within the past 2 years, with the following
exceptions:
- Malignancy treated with curative intent and with no known active disease
present for >2 years before enrollment and felt to be at low risk for
recurrence by the treating physician.
- Adequately treated non-melanoma skin cancer or lentigo maligna without
evidence of disease.
- Adequately treated cervical carcinoma in situ without evidence of disease.
- Adequately treated breast ductal carcinoma in situ without evidence of
disease.
- Prostatic intraepithelial neoplasia without evidence of prostate cancer.
- Adequately treated urothelial papillary non-invasive carcinoma or carcinoma
in situ.
• Myocardial infarction within 6 months of study day 1, symptomatic congestive
heart failure (New York Heart Association > class II), unstable angina, or
cardiac arrythmia requiring medication
• GI tract disease causing the inability to take oral medication, malabsorption
syndrome, requirement for IV alimentation, uncontrolled inflammatory GI disease
(eg, Crohn's disease, ulcerative colitis)
• Exclusion of hepatitis infection based on the following results and/or
criteria:
- Positive Hepatitis B Surface Antigen (HepBsAg) (indicative of chronic
Hepatitis B or recent acute hepatitis B)
- Negative HepBsAg with a positive for hepatitis B core antibody (Hepatitis B
core antibody testing is not required for screening, however if this is done
and is positive, then hepatitis B surface antibody [antiHBs] testing is
necessary. Undetectable anti-HBs in this setting would suggest unclear and
possible infection and needs exclusion).
- Positive Hepatitis C virus antibody: Hepatitis C virus RNA by polymerase
chain reaction (PCR) is necessary. Detectable Hepatitis C virus RNA suggests
chronic hepatitis C
• Known positive test for HIV
• Has an active infection requiring systemic therapy
• Received radiation therapy to the lung that is > 30 Gy within 6 months of the
first dose of trial treatment
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-506794-35-00 |
| EudraCT | EUCTR2020-004721-23-NL |
| ClinicalTrials.gov | NCT04185883 |
| CCMO | NL79714.056.21 |