Study of Irinotecan and AZD1775, a Selective Wee 1 Inhibitor, in RAS or BRAF Mutated, Second-line Metastatic Colorectal Cancer
Primary Purpose
Metastatic Colorectal Cancer
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
AZD1775
Irinotecan
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Colorectal Cancer focused on measuring RAS, KRAS, NRAS, BRAF, Mutated, Wee1 inhibitor
Eligibility Criteria
Inclusion Criteria:
- Provide signed and dated informed consent prior to any study specific procedures
- Age 18 years or older
- Histological or cytological confirmation of Colorectal Cancer (CRC) with available tissue, currently stage IV
- Failure of first-line anti-cancer therapy with an oxaliplatin and bevacizumab based regimen (either radiological documentation of disease progression or due to toxicity) or subsequent relapse of disease following first-line therapy. Patients relapsing within 12 months of completing adjuvant FOLFOX will also be considered eligible.
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - 1
- At least one lesion, not previously irradiated, that can be accurately measured as ≥ 10 mm in the longest diameter (LD) with spiral computed tomography (CT) scan or as ≥ 20 mm with conventional techniques (conventional CT, MRI) and which is suitable for accurate repeated measurements
- Tumor sample confirmed as KRAS or NRAS [codons 12 and 13 (exon 2), 59 and 61 (exon 3), and 117 and 146 (exon 4)] or BRAF [codon 600 (exon 15)] mutation positive.
- Patients must be able to swallow AZD1775 capsules
Exclusion Criteria:
- Treatment within 14 days prior to first study treatment with conventional therapy or treatment within 28 days prior to first study treatment with an investigational drug
- Received more than 1 line of systemic treatment for advanced/metastatic CRC and/or a patient whose first line therapy did not contain oxaliplatin and bevacizumab
- Prior treatment with a Wee1 inhibitor or any irinotecan containing regimen
- Any unresolved toxicity ≥ CTCAE Grade 2 from previous anti-cancer therapy, except for alopecia and neurotoxicity.
- The last radiation therapy within 4 weeks prior to starting study treatment, or limited field of radiation for palliation within 2 weeks of the first dose of study treatment
- Recent major surgery within 4 weeks prior to entry into the study (excluding the placement of vascular access) which would prevent administration of study treatment
- History of hypersensitivity to AZD1775, irinotecan, or any excipients of these agents
- Brain metastases or spinal cord compression unless asymptomatic, treated and stable off steroids and anti-convulsants for at least 3 months
Laboratory values as listed below (from laboratory results during screening):
- Absolute Neutrophil Count (ANC) <1.5 x 10^9/L (1500 per mm3)
- Platelets < 100 x 109/L (100,000 per mm3)
- Hemoglobin <9.0 g/dL
- Serum bilirubin >Upper Limit of Normal (ULN)
Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT):
- > 2.5 x ULN
- > 5 x ULN, if liver metastasis present
- Creatinine clearance < 50 cc/min measured or calculated by Cockcroft Gault equation - Cardiac conditions as follows:
- Uncontrolled hypertension (BP ≥ 170/100 despite optimal therapy)
- Heart failure New York Heart Association (NYHA) Class II or above
- Prior or current cardiomyopathy
- If NYHA Class I heart failure, Left Ventricular Ejection Fraction (LVEF) by Multi Gated Acquisition Scan (MUGA) or Echocardiogram (ECHO) is less than 50%
- Unstable ischemic heart disease (myocardial infarction within 6 months prior to starting treatment, or angina requiring use of nitrates more than once weekly)
- Mean resting corrected QT (QTc) interval using the Fridericia formula (QTcF) > 450 msec/male and > 470 msec/female (as calculated per institutional standards) obtained from 3 electrocardiograms (ECGs) 2-5 minutes apart at study entry, or congenital long QT syndrome
- Patients with significant ventricular or supraventricular arrhythmias and patients with cardiac conduction abnormalities that are not controlled (e.g. with a pacemaker or medication).
- Any evidence of severe or uncontrolled systemic disease, active infection, active bleeding diatheses or renal transplant, including any patient known to have hepatitis B, hepatitis C or human immunodeficiency virus (HIV)
- Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g., inflammatory bowel disease), or significant bowel resection that would preclude adequate ingestion and absorption of an oral agent
- Clinical evidence of bowel obstruction at the time of study entry
- Female patients who are pregnant or breast-feeding, or male or female patients of reproductive potential who are not employing an effective method of birth control
- History of another primary malignancy within 5 years prior to starting study treatment, except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ. Patients with an early stage cancer, now off therapy for at least 3 years may be enrolled with permission of the PI if that disease is unlikely to interfere with the primary endpoints of this study.
Sites / Locations
- Laura and Isaac Perlmutter Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
AZD1775 & Irinotecan
Arm Description
Group AZD1775 (study drug); Irinotecan (chemotherapy) 1) 125 mg two times a day (BID) for 3 days every 2 weeks; 180mg/m2 every 2 weeks 2A) 150 mg BID for 3 days every 2 weeks; 180mg/m2 every 2 weeks 2B) 125 mg BID for 5 days every 2 weeks; 180mg/m2 every 2 weeks 3) 150 mg BID for 5 days every 2 weeks ; 180mg/m2 every 2 weeks
Outcomes
Primary Outcome Measures
Number of participants dose limiting toxicities with treatment-related adverse events as assessed by common terminology criteria for adverse events (CTCAE), version 4.
Secondary Outcome Measures
Tumor assessment by imaging techniques using Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1
Full Information
NCT ID
NCT02906059
First Posted
September 9, 2016
Last Updated
October 8, 2020
Sponsor
NYU Langone Health
Collaborators
AstraZeneca
1. Study Identification
Unique Protocol Identification Number
NCT02906059
Brief Title
Study of Irinotecan and AZD1775, a Selective Wee 1 Inhibitor, in RAS or BRAF Mutated, Second-line Metastatic Colorectal Cancer
Official Title
A Phase Ib Study Combining Irinotecan With AZD1775, a Selective Wee 1 Inhibitor, in RAS (KRAS or NRAS) or BRAF Mutated Metastatic Colorectal Cancer Patients Who Have Progressed on First Line Therapy
Study Type
Interventional
2. Study Status
Record Verification Date
October 2020
Overall Recruitment Status
Completed
Study Start Date
September 2016 (undefined)
Primary Completion Date
March 12, 2020 (Actual)
Study Completion Date
March 12, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NYU Langone Health
Collaborators
AstraZeneca
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to determine whether combination therapy of irinotecan with AZD1775 is safe and effective in treating mutated metastatic colorectal cancer patients.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer
Keywords
RAS, KRAS, NRAS, BRAF, Mutated, Wee1 inhibitor
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
7 (Actual)
8. Arms, Groups, and Interventions
Arm Title
AZD1775 & Irinotecan
Arm Type
Experimental
Arm Description
Group AZD1775 (study drug); Irinotecan (chemotherapy)
1) 125 mg two times a day (BID) for 3 days every 2 weeks; 180mg/m2 every 2 weeks
2A) 150 mg BID for 3 days every 2 weeks; 180mg/m2 every 2 weeks
2B) 125 mg BID for 5 days every 2 weeks; 180mg/m2 every 2 weeks
3) 150 mg BID for 5 days every 2 weeks ; 180mg/m2 every 2 weeks
Intervention Type
Drug
Intervention Name(s)
AZD1775
Intervention Type
Drug
Intervention Name(s)
Irinotecan
Other Intervention Name(s)
Camptosar, Campto
Primary Outcome Measure Information:
Title
Number of participants dose limiting toxicities with treatment-related adverse events as assessed by common terminology criteria for adverse events (CTCAE), version 4.
Time Frame
Up to 12 months
Secondary Outcome Measure Information:
Title
Tumor assessment by imaging techniques using Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1
Time Frame
From baseline to every 8 weeks up to 12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Provide signed and dated informed consent prior to any study specific procedures
Age 18 years or older
Histological or cytological confirmation of Colorectal Cancer (CRC) with available tissue, currently stage IV
Failure of first-line anti-cancer therapy with an oxaliplatin and bevacizumab based regimen (either radiological documentation of disease progression or due to toxicity) or subsequent relapse of disease following first-line therapy. Patients relapsing within 12 months of completing adjuvant FOLFOX will also be considered eligible.
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - 1
At least one lesion, not previously irradiated, that can be accurately measured as ≥ 10 mm in the longest diameter (LD) with spiral computed tomography (CT) scan or as ≥ 20 mm with conventional techniques (conventional CT, MRI) and which is suitable for accurate repeated measurements
Tumor sample confirmed as KRAS or NRAS [codons 12 and 13 (exon 2), 59 and 61 (exon 3), and 117 and 146 (exon 4)] or BRAF [codon 600 (exon 15)] mutation positive.
Patients must be able to swallow AZD1775 capsules
Exclusion Criteria:
Treatment within 14 days prior to first study treatment with conventional therapy or treatment within 28 days prior to first study treatment with an investigational drug
Received more than 1 line of systemic treatment for advanced/metastatic CRC and/or a patient whose first line therapy did not contain oxaliplatin and bevacizumab
Prior treatment with a Wee1 inhibitor or any irinotecan containing regimen
Any unresolved toxicity ≥ CTCAE Grade 2 from previous anti-cancer therapy, except for alopecia and neurotoxicity.
The last radiation therapy within 4 weeks prior to starting study treatment, or limited field of radiation for palliation within 2 weeks of the first dose of study treatment
Recent major surgery within 4 weeks prior to entry into the study (excluding the placement of vascular access) which would prevent administration of study treatment
History of hypersensitivity to AZD1775, irinotecan, or any excipients of these agents
Brain metastases or spinal cord compression unless asymptomatic, treated and stable off steroids and anti-convulsants for at least 3 months
Laboratory values as listed below (from laboratory results during screening):
Absolute Neutrophil Count (ANC) <1.5 x 10^9/L (1500 per mm3)
Platelets < 100 x 109/L (100,000 per mm3)
Hemoglobin <9.0 g/dL
Serum bilirubin >Upper Limit of Normal (ULN)
Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT):
> 2.5 x ULN
> 5 x ULN, if liver metastasis present
Creatinine clearance < 50 cc/min measured or calculated by Cockcroft Gault equation - Cardiac conditions as follows:
Uncontrolled hypertension (BP ≥ 170/100 despite optimal therapy)
Heart failure New York Heart Association (NYHA) Class II or above
Prior or current cardiomyopathy
If NYHA Class I heart failure, Left Ventricular Ejection Fraction (LVEF) by Multi Gated Acquisition Scan (MUGA) or Echocardiogram (ECHO) is less than 50%
Unstable ischemic heart disease (myocardial infarction within 6 months prior to starting treatment, or angina requiring use of nitrates more than once weekly)
Mean resting corrected QT (QTc) interval using the Fridericia formula (QTcF) > 450 msec/male and > 470 msec/female (as calculated per institutional standards) obtained from 3 electrocardiograms (ECGs) 2-5 minutes apart at study entry, or congenital long QT syndrome
Patients with significant ventricular or supraventricular arrhythmias and patients with cardiac conduction abnormalities that are not controlled (e.g. with a pacemaker or medication).
Any evidence of severe or uncontrolled systemic disease, active infection, active bleeding diatheses or renal transplant, including any patient known to have hepatitis B, hepatitis C or human immunodeficiency virus (HIV)
Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g., inflammatory bowel disease), or significant bowel resection that would preclude adequate ingestion and absorption of an oral agent
Clinical evidence of bowel obstruction at the time of study entry
Female patients who are pregnant or breast-feeding, or male or female patients of reproductive potential who are not employing an effective method of birth control
History of another primary malignancy within 5 years prior to starting study treatment, except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ. Patients with an early stage cancer, now off therapy for at least 3 years may be enrolled with permission of the PI if that disease is unlikely to interfere with the primary endpoints of this study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Deirdre Cohen, MD
Organizational Affiliation
NYU Perlmutter Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Laura and Isaac Perlmutter Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Study of Irinotecan and AZD1775, a Selective Wee 1 Inhibitor, in RAS or BRAF Mutated, Second-line Metastatic Colorectal Cancer
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