Metastatic Colorectal Cancer (CRC)Phase 1NCT04627142
A Study to Test Different Doses of BI 1701963 in Combination With Irinotecan in People With Advanced Bowel Cancer With Kirsten Rat Sarcoma Viral Oncogene Homologue (KRAS) Mutation
A Phase 1 study testing BI 1701963 and Camptosar® in people with Metastatic Colorectal Cancer (CRC), run by Boehringer Ingelheim at 1 site in China.
Trial summary
This study is open to adults with advanced bowel cancer (colorectal cancer) with a KRAS mutation. This is a study in people for whom previous treatment was not successful and surgery is not a treatment option. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer (CRC)
- What is being tested?
- BI 1701963 and Camptosar®
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteChina
- Study dates
- 23 Nov 2020to 18 Jan 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Patient must have a confirmed activating KRAS mutation in CRC tumour tissue by local test. Activating mutations include but are not limited to: KRAS mutations in exon 2 (G12, G13), exon 3 (A59, Q61) and exon 4 (K117, A146)
- Patients must have a histological or cytological diagnosis of CRC
- Patients must have received at least first-line chemotherapy (oxaliplatin/ 5-Fluorouracil (5-FU)/ capecitabine et al treatment failure) for unresectable locally advanced or metastatic CRC
- Must have at least one target lesion that can be accurately measured per RECIST version 1.1
- Must have Eastern Cooperative Oncology Group score of 0 or 1
- Must show adequate organ function defined as all of the following:
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- Absolute neutrophil count (ANC) ≥1.5 x 109/L; haemoglobin ≥9.0 g/dL; platelets ≥100 x 109/L without the use of hematopoietic growth factors within 4 weeks of start of Trial medication.
- Total bilirubin ≤1.5 x Upper Limited of Normal (ULN), or ≤4 x ULN for patients who are known to have Gilbert's syndrome
- Creatinine ≤1.5 x ULN. If creatinine is >1.5 x ULN, patient is eligible if concurrent glomerular filtration rate (GFR) ≥30 mL/min (measured or calculated by CKD-EPI formula)
- Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤3 x ULN if no demonstrable liver metastases, or otherwise ≤5 x ULN
- For patients participating in the combination dose escalation and expansion parts (Part B and C), must be eligible to receive treatment with irinotecan in accordance with the local label including Summary of Product Characteristics (SmPC), U.S. PI or Chinese Label
- Must be at least 18 years of age at screening
- Must have recovered from any previous therapy related toxicity to CTCAE grade ≤1 before the first dose (except for alopecia; stable sensory neuropathy must be CTCAE grade ≤2)
- Signed and dated written informed consent in accordance with good clinical practice and local legislation prior to admission to the trial
- further inclusion criteria apply
Who cannot join
- Previous anticancer chemotherapy, anticancer immunotherapy, and/or other anticancer biologic therapy within 3 weeks of the first administration of trial drug. Previous anticancer hormonal therapy within 2 weeks of first administration of trial drug
- Previous treatment with a RAS, Mitogen-activated protein kinase (MAPK) or Son of Sevenless 1 (SOS1) targeting agent
- For patients participating in the combination dose escalation and expansion parts (Part B and C only): Previous treatment with irinotecan
- Radiotherapy within 4 weeks except as follows
- Palliative radiotherapy to regions other than the chest is allowed up to 2 weeks prior to start of treatment
- Single dose palliative radiotherapy for symptomatic metastasis within 2 weeks prior to start of treatment may be allowed but must be discussed with the sponsor
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- Major surgery (major according to the investigator's assessment) performed within 4 weeks prior to start of treatment or planned during the projected course of the trial, e.g. hip replacement
- Previous treatment with any investigational agent(s) or targeted treatment within 28 days prior to start of treatment
- Known history of hypersensitivity to any of the excipients of BI 1701963 tablets
- History or presence of cardiovascular abnormalities such as uncontrolled Hypertension, congestive heart failure New York Heart Association (NYHA) classification of ≥3, unstable angina or poorly controlled arrhythmia which are considered as clinically relevant by the investigator; Myocardial infarction within 6 months prior to start of treatment
- Left ventricular ejection fraction (LVEF) <50%
- Congenital long QT prolongation syndrome or mean resting corrected QT interval (QTcF) >470 msec
- further exclusion criteria apply
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1 Open-label Dose Escalation Trial of BI 1701963 in Combination With Irinotecan in KRAS Mutation Positive Patients With Unresectable Locally Advanced or Metastatic Colorectal Cancer
This study is open to adults with advanced bowel cancer (colorectal cancer) with a KRAS mutation. This is a study in people for whom previous treatment was not successful and surgery is not a treatment option.
The purpose of this study is to find the highest dose of BI 1701963 that people with bowel cancer can tolerate when taken together with a medicine called irinotecan. The study also tests whether BI 1701963 in combination with irinotecan is able to make tumours shrink. BI 1701963 may help to turn off KRAS. Activating KRAS mutations make tumours grow. Irinotecan is a medicine to treat bowel cancer.
Read more
Participants can stay in the study as long as they benefit from treatment and can tolerate it.
During this time, participants take BI 1701963 as tablet once a day and get irinotecan as infusion every two weeks. The doctors regularly monitor the size of the tumour. The doctors also collect information on any health problems of the participants.
- Conditions
- Metastatic Colorectal Cancer (CRC)
- Being tested
- BI 1701963, Camptosar®
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BI 1701963Drug
Tablet
Camptosar®Drug
Solution for infusion
| Study group | Role | What they receive |
|---|---|---|
| Expansion dose 1 | Experimental | Part C: Combination therapy expansion part Receives: Drug: BI 1701963; Drug: Camptosar® |
| Expansion dose 2 | Experimental | Part C: Combination therapy expansion part Receives: Drug: BI 1701963; Drug: Camptosar® |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD) based on the number of dose limiting toxicities (DLTs) in the MTD evaluation period
Combination dose escalation part (Part B)
Measured: 28 days
Number of patients experiencing DLTs in the MTD evaluation period
Combination dose escalation part (Part B)
Measured: 28 days
Objective Response (OR) according to RECIST version 1.1
Combination therapy expansion part (Part C)
Measured: 28 days per treatment cycle.
Secondary outcomes (9)
Number of patients with DLTs in the first treatment cycle
Monotherapy safety run-in part (Part A)
Measured: 28 days
Maximum measured concentration of BI 1701963 in plasma (Cmax)
Monotherapy safety run-in part (Part A)
Measured: 28 days per treatment cycle.
Area under the concentration time curve of BI 1701963 in plasma over the time interval from 0 to the last quantifiable plasma concentration (AUC0-tz)
Monotherapy safety run-in part (Part A)
Measured: 28 days per treatment cycle.
Area under the concentration-time curve of BI 1701963 in plasma over the dosing interval τ at steady state (AUCτ(,ss))
Monotherapy safety run-in and combination dose escalation part (Part A+B)
Measured: 28 days per treatment cycle.
Maximum measured concentration of BI 1701963 in plasma at steady state over a uniform dosing interval tau (Cmax,ss)
Monotherapy safety run-in and combination dose escalation part (Part A+B)
Measured: 28 days per treatment cycle.
Duration of objective response (DOR)
Combination therapy expansion part (Part C)
Measured: 28 days per treatment cycle.
Tumour shrinkage (in millimetres)
Combination therapy expansion part (Part C)
Measured: 28 days per treatment cycle.
Progression-free survival (PFS)
Combination therapy expansion part (Part C)
Measured: Up to 6 months.
Number of patients experiencing grade ≥3 treatment-related AEs during the entire treatment period
Combination therapy expansion part (Part C)
Measured: 28 days per treatment cycle.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2020
- Study start23 Nov 2020
- Primary completion18 Jan 2022
- Study completion18 Jan 2022
Why it stopped: Sponsor decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Colorectal Cancer (CRC)Studies of the same condition, open and under way.
- More trials run by Boehringer IngelheimThe sponsor's other registered studies.
- 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Trial consists of three parts: Monotherapy safety run-in part (Part A), combination dose escalation part (Part B), combination therapy expansion part (Part C). A randomization will be included for the expansion therapy part (Part C) because the same patient population will be recruited to two different dose levels at the same time.
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04627142
- Sponsor's protocol ID
- 1432-0008
- Status last verified
- Apr 2022
- First submitted
- 10 Nov 2020
- Last updated
- 20 Apr 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions: 1\. studies in products where Boehringer Ingelheim is not the license holder; 2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; 3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datasharing
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Open-label Dose Escalation Trial of BI 1701963 in Combination With Irinotecan in KRAS Mutation Positive Patients With Unresectable Locally Advanced or Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT04627142
- Acronym / sponsor ID
- 1432-0008
- Conditions
- Metastatic Colorectal Cancer (CRC)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decision
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- 23 Nov 2020 (actual)
- Primary completion
- 18 Jan 2022 (actual)
- Study completion
- 18 Jan 2022 (actual)
- First posted
- 13 Nov 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is open to adults with advanced bowel cancer (colorectal cancer) with a KRAS mutation. This is a study in people for whom previous treatment was not successful and surgery is not a treatment option.
The purpose of this study is to find the highest dose of BI 1701963 that people with bowel cancer can tolerate when taken together with a medicine called irinotecan. The study also tests whether BI 1701963 in combination with irinotecan is able to make tumours shrink. BI 1701963 may help to turn off KRAS. Activating KRAS mutations make tumours grow. Irinotecan is a medicine to treat bowel cancer.
Participants can stay in the study as long as they benefit from treatment and can tolerate it.
During this time, participants take BI 1701963 as tablet once a day and get irinotecan as infusion every two weeks. The doctors regularly monitor the size of the tumour. The doctors also collect information on any health problems of the participants.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Trial consists of three parts: Monotherapy safety run-in part (Part A), combination dose escalation part (Part B), combination therapy expansion part (Part C). A randomization will be included for the expansion therapy part (Part C) because the same patient population will be recruited to two different dose levels at the same time.
| Arm | Type | Receives |
|---|---|---|
| Expansion dose 1 | Experimental | Drug: BI 1701963, Drug: Camptosar®Part C: Combination therapy expansion part |
| Expansion dose 2 | Experimental | Drug: BI 1701963, Drug: Camptosar®Part C: Combination therapy expansion part |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Patient must have a confirmed activating KRAS mutation in CRC tumour tissue by local test. Activating mutations include but are not limited to: KRAS mutations in exon 2 (G12, G13), exon 3 (A59, Q61) and exon 4 (K117, A146)
- Patients must have a histological or cytological diagnosis of CRC
- Patients must have received at least first-line chemotherapy (oxaliplatin/ 5-Fluorouracil (5-FU)/ capecitabine et al treatment failure) for unresectable locally advanced or metastatic CRC
- Must have at least one target lesion that can be accurately measured per RECIST version 1.1
- Must have Eastern Cooperative Oncology Group score of 0 or 1
Key exclusion criteria (13 listed)
- Previous anticancer chemotherapy, anticancer immunotherapy, and/or other anticancer biologic therapy within 3 weeks of the first administration of trial drug. Previous anticancer hormonal therapy within 2 weeks of first administration of trial drug
- Previous treatment with a RAS, Mitogen-activated protein kinase (MAPK) or Son of Sevenless 1 (SOS1) targeting agent
- For patients participating in the combination dose escalation and expansion parts (Part B and C only): Previous treatment with irinotecan
- Radiotherapy within 4 weeks except as follows
- Major surgery (major according to the investigator's assessment) performed within 4 weeks prior to start of treatment or planned during the projected course of the trial, e.g. hip replacement
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 |
|---|---|---|
| BI 1701963Tablet | Drug | Expansion dose 1, Expansion dose 2 |
| Camptosar®Solution for infusion | Drug | Expansion dose 1, Expansion dose 2 |
Primary outcome
Maximum tolerated dose (MTD) based on the number of dose limiting toxicities (DLTs) in the MTD evaluation period
Time frame: 28 days
Combination dose escalation part (Part B)
Number of patients experiencing DLTs in the MTD evaluation period
Time frame: 28 days
Combination dose escalation part (Part B)
Objective Response (OR) according to RECIST version 1.1
Time frame: 28 days per treatment cycle.
Combination therapy expansion part (Part C)
9 secondary outcomes
Number of patients with DLTs in the first treatment cycle
Time frame: 28 days
Maximum measured concentration of BI 1701963 in plasma (Cmax)
Time frame: 28 days per treatment cycle.
Area under the concentration time curve of BI 1701963 in plasma over the time interval from 0 to the last quantifiable plasma concentration (AUC0-tz)
Time frame: 28 days per treatment cycle.
Area under the concentration-time curve of BI 1701963 in plasma over the dosing interval τ at steady state (AUCτ(,ss))
Time frame: 28 days per treatment cycle.
Maximum measured concentration of BI 1701963 in plasma at steady state over a uniform dosing interval tau (Cmax,ss)
Time frame: 28 days per treatment cycle.
Duration of objective response (DOR)
Time frame: 28 days per treatment cycle.
Tumour shrinkage (in millimetres)
Time frame: 28 days per treatment cycle.
Progression-free survival (PFS)
Time frame: Up to 6 months.
Number of patients experiencing grade ≥3 treatment-related AEs during the entire treatment period
Time frame: 28 days per treatment cycle.
Results and safety
The study was stopped early (reason given: Sponsor decision). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2022.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: No. Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions: 1. studies in products where Boehringer Ingelheim is not the license holder; 2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; 3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datasharing
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BI 1701963 and Camptosar® in people with Metastatic Colorectal Cancer (CRC), run by Boehringer Ingelheim at 1 site in China.
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 15 inclusion and 13 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 20 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Sponsor decision). Results are not available in the source record.
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?
Maximum tolerated dose (MTD) based on the number of dose limiting toxicities (DLTs) in the MTD evaluation period (time frame: 28 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 Apr 2022.