Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001690842
Ethics application status
Approved
Date submitted
4/11/2021
Date registered
10/12/2021
Date last updated
20/02/2024
Date data sharing statement initially provided
10/12/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Cancer Molecular Screening and Therapeutics (MoST) Program Addendum 19 substudies 41-42: Sotorasib
Scientific title
Single arm, open label, signal-seeking phase II study of Sotorasib (AMG-510) in patients with solid tumours harbouring KRAS G12C mutation.
Secondary ID [1] 305725 0
CTC 0141 – addendum 19
Universal Trial Number (UTN)
U1111-1182-6652
Trial acronym
MoST addendum 19
Linked study record
This record is an addendum to the MoST framework (ACTRN12616000908437). The MoST framework protocol consists of 1/molecular screening (genomic analysis to determine whether participants are suitable for a sub-study) and 2/ sub-study design structure (study treatment for specific genomic expression/participant population). Additionally, the sub-study shares the same study objectives and outcomes as the framework. Hence, this is a substudy that linked to ACTRN12616000908437.

Health condition
Health condition(s) or problem(s) studied:
Cancer 324207 0
Condition category
Condition code
Cancer 321691 321691 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
8x oral tablets of 120 mg Sotorasib for a total daily dose of 960 mg. Tablets will be taken continuously over 28 day cycles until disease progression.

Participants will be asked to return unused drug and empty drug containers at each return visit. The Pharmacy Department at participating institutions will maintain a record of drugs dispensed for each participant.
Intervention code [1] 322122 0
Treatment: Drugs
Comparator / control treatment
No control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 329457 0
To assess the clinical anti-tumour activity of Sotorasib in solid tumours that harbour KRAS G12C mutation, as assessed by objective tumour response (OTR), based on complete or partial response using cancer specific response criteria from RECIST v1.1 and/or RANO. Where disease evaluation is not based on imaging scans (eg. CT/MRI), clinical assessment of response may be utilised. Response is assigned based on investigator discretion.
Timepoint [1] 329457 0
Imaging (eg. CT) scans for disease evaluation will take place on cycle 2 day 1, cycle 3 day 1 (primary endpoint), and every 8 weeks from cycle 5 until disease progression (primary endpoint; n.b., each cycle is 28 days). Clinical assessment of response will be assessed at the same timepoints
Secondary outcome [1] 402679 0
To determine the ratio of time-to-progression. This will be assessed by imaging (e.g. CT/MRI).
Timepoint [1] 402679 0
Participants will be followed up for disease progression on cycle 2 day 1 , cycle 3 day 1, and every 8 weeks from cycle 5 until disease progression (n.b. each cycle is 28 days)
Secondary outcome [2] 402680 0
Progression free survival at 6 months. This will be assessed by imaging (e.g. CT/MRI).
Timepoint [2] 402680 0
Participants will be assessed for disease progression at 6 months post-intervention commencement.
Secondary outcome [3] 402681 0
Progression free survival (PFS). PFS is defined as the interval from date of registration to the date of first evidence of disease progression or death from any cause, whichever occurs first. This will be classified as stable, partial response, or complete response according to RECISTv1.1 and iRECIST as assessed by imaging (e.g. CT scans).
Timepoint [3] 402681 0
Participants will be followed up for disease progression on cycle 2 day 1 , cycle 3 day 1, and every 8 weeks from cycle 5 until disease progression (n.b. each cycle is 28 days) for the duration of the study.
Secondary outcome [4] 402682 0
Overall survival at 12 months (death from any cause). This will be assessed by reviewing medical records.
Timepoint [4] 402682 0
At 12 months post intervention commencement, from the date of registration to date of death from any cause, or the date of last known follow-up alive.
Secondary outcome [5] 402683 0
Overall survival (OS) (death from any cause). This will be assessed by reviewing medical records.
Timepoint [5] 402683 0
For the duration of the study. From the date of registration to date of death from any cause, or the date of last known follow-up alive.
Secondary outcome [6] 402684 0
Safety and tolerability of treatment (rates of adverse events). All adverse events (AEs), including event grading as per NCI CTCAE criteria, will be captured from the first dose of study treatment until 28 days after cessation of study treatment. Reported AEs (eg. diarrhoea, gastrointestinal disorder) by participants will be documented by study site staff and subsequently transcript onto study electronic data capturing (EDC) system. In order to evaluate the safety and tolerability of the study treatment, the entered AE types, frequency and severity in the EDC will be analysed.
Timepoint [6] 402684 0
Adverse events will be recorded from the first dose of study treatment until 28 days after cessation of study treatment.
Secondary outcome [7] 402685 0
Health related quality of life during treatment will be assessed by the EORTC QLQ-C30.
Timepoint [7] 402685 0
While on treatment, health related quality of life will be assessed at baseline, every 8 weeks for the first 6 months after treatment commencement, then every 12 weeks (+/- 7 days) until progression.
Secondary outcome [8] 403313 0
Health related quality of life during treatment will be assessed by the Brief Pain Inventory Forms.
Timepoint [8] 403313 0
While on treatment, health related quality of life will be assessed at baseline, every 8 weeks for the first 6 months after treatment commencement, then every 12 weeks (+/- 7 days) until progression.

Eligibility
Key inclusion criteria
1. Adults, aged 18 years and older, with pathologically confirmed advanced and/or metastatic solid cancer of any histologic type or an earlier diagnosis of a poor prognosis cancer.
2. ECOG performance status 0, 1 or 2;
3. Confirmation of KRAS G12C mutation in the tumour tissue by the next generation sequencing (NGS) panel. Patients who have a positive KRAS G12C mutation determined by a recognised assay may be eligible after discussion with the study chair. Patient should have adequate specimen (archival tissue or biopsy) for full molecular screening;
4. Confirmation of molecular eligibility by the molecular tumour board;
5. Life expectancy greater than or equal to 12 weeks;
6. Received and failed all standard anticancer therapy or have documented unsuitability for any further standard therapy, if standard therapy exists;
7. Clinical or radiological progression on or following last anticancer therapy unless such anticancer therapy stopped due to toxicity / treatment intolerance;
8. Measurable disease as assessed by RECIST 1.1 or RANO;
9. Adequate organ system function as assessed by the following minimal laboratory requirements (within 14 days prior to first administration of study drug):
a. Bone marrow function; platelets greater than or equal to 100 × 109/L, ANC greater than or equal to 1.5 × 109/L, and haemoglobin greater than or equal to 90 g/L;
b. Liver function; ALT/AST less than or equal to 3 × ULN (in the absence of liver metastases, less than or equal to 5 × ULN for patients with liver involvement) and total bilirubin less than or equal to 1.5 × ULN;
10. Renal function; serum creatinine less than or equal to 1.5 × ULN;
11. QTc less than or equal to 470 msec (based on average of screening triplicates)
12. Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments
13. Signed, written informed consent to participation in the specific treatment substudy.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Contraindications to investigational product;
2. Known history of hypersensitivity to active or inactive components of investigational product;
3. History of prior KRAS G12C inhibitor treatment. Prior treatment or participation in a clinical trial with an inhibitor of Mitogen-activated protein kinase (MAPK) or other KRAS-targeting agent is allowed;
4. Patients with non-small cell lung cancer (NSCLC) or colorectal cancer are ineligible;
5. Specific comorbidities or conditions (e.g., psychiatric) or concomitant medications which may interact with the investigational product;
6. Co-morbidities or conditions that may compromise assessment of key outcomes or in the opinion of the clinician, limit the ability of the patient to comply with the protocol;
7. Treatment with any of the following anti-cancer therapies prior to the first dose of study treatment:
a. Radiation therapy, major surgery, or tumour embolization within 14 days prior to the first dose of study treatment. Palliative radiotherapy (for analgesia) is acceptable only if the irradiated field does not include target lesions;
b. Immunotherapy within 28 days prior to the first dose of study treatment;
c. Chemotherapy, biologic therapy or hormonal therapy within 28 days of a drug prior to the first dose of study treatment or until recovery from previous therapy (whichever is longer);
d. Any unresolved toxicity (greater than CTCAE grade 2) from previous anti-cancer therapy. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included;
8. Administration of any investigational treatment within 28 days or 5 half-lives (whichever is longer) prior to receiving the first dose of study treatment;
9. Use of any of the following agents within 14 days or 5 half-lives of the drug or its major active metabolite, whichever is longer, prior to study day 1 that was not reviewed and approved by the principal investigator: (1) known cytochrome P450 CYP3A4 sensitive or P-gp substrates with a narrow therapeutic window, (2) strong inhibitors of CYP3A4, (3) grapefruit juice or grapefruit containing products, (4) strong inducers of CYP3A4 (including St. John's wort)
10. For non-central nervous system (CNS) cancers, patients with symptomatic CNS involvement of his/her cancer are excluded. Subjects with stable neurological function, on stable doses of steroids/anti-epileptics over 4 weeks, and with no evidence of CNS progression within 12 weeks prior to screening are eligible;
11. Active hepatitis infection based on the following results and/or criteria:
a. Positive Hepatitis B Surface Antigen (HBsAg);
b. Negative HBsAg with a positive for hepatitis B core antibody (HBcAb);
c. Positive Hepatitis C virus antibody: Hepatitis C virus RNA by PCR is necessary. Detectable Hepatitis C virus RNA suggests chronic hepatitis C;
12. Known positive test for HIV;
13. Prior or concurrent malignancy. For participants with treatment-refractory solid tumours, a concurrent or past history of competing malignancy within 2 years, prior to molecular screening registration, is eligible, unless the competing malignancy is expected to lead to a shorter survival than the index KRAS G12C-harbouring malignancy;
14. Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal, infertile, or use a reliable means of contraception. Hormonal-based contraception are not allowed. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to registration. Men must have been surgically sterilized or use a (double if required) barrier method of contraception.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis
32 patients will be treated with Sotorasib selected on the basis of KRAS G12C mutations. A study with greater than or equal to 7/32 responding participants will be considered sufficiently interesting to investigate further.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
7/02/2022
Actual
7/07/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
32
Accrual to date
3
Final
Recruitment in Australia
Recruitment state(s)
NSW,NT,SA,TAS,WA,VIC
Recruitment hospital [1] 21027 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [2] 21028 0
Royal Hobart Hospital - Hobart
Recruitment hospital [3] 21029 0
Linear Clinical Research - Nedlands
Recruitment hospital [4] 21030 0
Garvan Institute of Medical Research - Darlinghurst
Recruitment hospital [5] 21032 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [6] 21186 0
Westmead Hospital - Westmead
Recruitment hospital [7] 23112 0
Royal Darwin Hospital - Tiwi
Recruitment postcode(s) [1] 35866 0
3000 - Melbourne
Recruitment postcode(s) [2] 35867 0
7000 - Hobart
Recruitment postcode(s) [3] 35868 0
6009 - Nedlands
Recruitment postcode(s) [4] 35869 0
2010 - Darlinghurst
Recruitment postcode(s) [5] 35871 0
5000 - Adelaide
Recruitment postcode(s) [6] 36050 0
2145 - Westmead
Recruitment postcode(s) [7] 38472 0
0810 - Tiwi

Funding & Sponsors
Funding source category [1] 310083 0
Government body
Name [1] 310083 0
Office for Health and Medical Research
Country [1] 310083 0
Australia
Funding source category [2] 310084 0
Other Collaborative groups
Name [2] 310084 0
Australian Genomic Cancer Medicine Centre (AGCMC)
Country [2] 310084 0
Australia
Primary sponsor type
University
Name
The University of Sydney
Address
NHMRC Clinical Trials Centre
Locked Bag 77
Camperdown NSW 1450
Country
Australia
Secondary sponsor category [1] 311143 0
Other Collaborative groups
Name [1] 311143 0
Australian Genomic Cancer Medicine Centre (AGCMC)
Address [1] 311143 0
Kinghorn Cancer Centre,
370 Victoria Street,
Darlinghurst NSW 2010
Country [1] 311143 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309773 0
St Vincent's Hospital Human Research Ethics Committee
Ethics committee address [1] 309773 0
Ethics committee country [1] 309773 0
Australia
Date submitted for ethics approval [1] 309773 0
30/08/2021
Approval date [1] 309773 0
07/10/2021
Ethics approval number [1] 309773 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 115342 0
Prof Jayesh Desai
Address 115342 0
Department of Medical Oncology
Peter MacCallum Cancer Centre
Victorian Comprehensive Cancer Centre (VCCC)
305 Grattan St,
Melbourne, Victoria
3000 Australia
Country 115342 0
Australia
Phone 115342 0
+61 3 9656 1190
Fax 115342 0
Email 115342 0
[email protected]
Contact person for public queries
Name 115343 0
Lucille Sebastian
Address 115343 0
NHMRC Clinical Trials Centre,
Medical Foundation Building,
Levels 4-6,
92-94 Parramatta Road,
Camperdown NSW 2050
Country 115343 0
Australia
Phone 115343 0
+61 2 9562 5000
Fax 115343 0
Email 115343 0
[email protected]
Contact person for scientific queries
Name 115344 0
Jayesh Desai
Address 115344 0
Department of Medical Oncology
Peter MacCallum Cancer Centre
Victorian Comprehensive Cancer Centre (VCCC)
305 Grattan St,
Melbourne, Victoria
3000 Australia
Country 115344 0
Australia
Phone 115344 0
+61 3 8559 5000
Fax 115344 0
Email 115344 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
There are no plans for this to occur at this time and participant consent is required for data sharing.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.