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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

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04627142
Recruitment Status : Terminated (Sponsor decision)
First Posted : November 13, 2020
Last Update Posted : April 20, 2022
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Brief 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.

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.


Condition or disease Intervention/treatment Phase
Metastatic Colorectal Cancer (CRC) Drug: BI 1701963 Drug: Camptosar® Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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)
Primary Purpose: Treatment
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
Actual Study Start Date : November 23, 2020
Actual Primary Completion Date : January 18, 2022
Actual Study Completion Date : January 18, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Expansion dose 1
Part C: Combination therapy expansion part
Drug: BI 1701963
Tablet

Drug: Camptosar®
Solution for infusion

Experimental: Expansion dose 2
Part C: Combination therapy expansion part
Drug: BI 1701963
Tablet

Drug: Camptosar®
Solution for infusion




Primary Outcome Measures :
  1. 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)

  2. Number of patients experiencing DLTs in the MTD evaluation period [ Time Frame: 28 days ]
    Combination dose escalation part (Part B)

  3. Objective Response (OR) according to RECIST version 1.1 [ Time Frame: 28 days per treatment cycle. ]
    Combination therapy expansion part (Part C)


Secondary Outcome Measures :
  1. Number of patients with DLTs in the first treatment cycle [ Time Frame: 28 days ]
    Monotherapy safety run-in part (Part A)

  2. Maximum measured concentration of BI 1701963 in plasma (Cmax) [ Time Frame: 28 days per treatment cycle. ]
    Monotherapy safety run-in part (Part A)

  3. 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. ]
    Monotherapy safety run-in part (Part A)

  4. 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. ]
    Monotherapy safety run-in and combination dose escalation part (Part A+B)

  5. 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. ]
    Monotherapy safety run-in and combination dose escalation part (Part A+B)

  6. Duration of objective response (DOR) [ Time Frame: 28 days per treatment cycle. ]
    Combination therapy expansion part (Part C)

  7. Tumour shrinkage (in millimetres) [ Time Frame: 28 days per treatment cycle. ]
    Combination therapy expansion part (Part C)

  8. Progression-free survival (PFS) [ Time Frame: Up to 6 months. ]
    Combination therapy expansion part (Part C)

  9. Number of patients experiencing grade ≥3 treatment-related AEs during the entire treatment period [ Time Frame: 28 days per treatment cycle. ]
    Combination therapy expansion part (Part C)



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:

  • 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:

    1. 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.
    2. Total bilirubin ≤1.5 x Upper Limited of Normal (ULN), or ≤4 x ULN for patients who are known to have Gilbert's syndrome
    3. 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)
    4. 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

Exclusion Criteria:

  • 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
  • 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

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): NCT04627142


Locations
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China
Shanghai East Hospital, Tongji University China
Shanghai, China, 200120
Sponsors and Collaborators
Boehringer Ingelheim
Additional Information:
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Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT04627142    
Other Study ID Numbers: 1432-0008
First Posted: November 13, 2020    Key Record Dates
Last Update Posted: April 20, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description:

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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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Irinotecan
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents