Metastatic Colorectal CancerPhase 1NCT02906059
Study of Irinotecan and AZD1775, a Selective Wee 1 Inhibitor, in RAS or BRAF Mutated, Second-line Metastatic Colorectal Cancer
A Phase 1 study testing AZD1775 and Irinotecan in people with Metastatic Colorectal Cancer, run by NYU Langone Health at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- AZD1775 and Irinotecan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2016to 12 Mar 2020
- 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
- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Laura and Isaac Perlmutter Cancer Center
New York, New York, 10016
About this study
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
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.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- AZD1775, Irinotecan
- Keywords
- RAS, KRAS, NRAS, BRAF, Mutated, Wee1 inhibitor
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD1775Drug
IrinotecanDrug
Also called Camptosar, Campto
| Study group | Role | What they receive |
|---|---|---|
| AZD1775 & Irinotecan | Experimental | 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 Receives: Drug: AZD1775; Drug: Irinotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants dose limiting toxicities with treatment-related adverse events as assessed by common terminology criteria for adverse events (CTCAE), version 4.
Measured: Up to 12 months
Secondary outcomes (1)
Tumor assessment by imaging techniques using Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1
Measured: From baseline to every 8 weeks up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2016 (estimated)
- Study startSep 2016
- Primary completion12 Mar 2020
- Study completion12 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Colorectal CancerStudies of the same condition, open and under way.
- More trials run by NYU Langone HealthThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor
- Investigators
- Deirdre Cohen, MD, Principal investigator, NYU Perlmutter Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02906059
- Sponsor's protocol ID
- 14-01168
- Status last verified
- Oct 2020
- First submitted
- 9 Sep 2016
- Last updated
- 12 Oct 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02906059
- Acronym / sponsor ID
- 14-01168
- Conditions
- Metastatic Colorectal Cancer
- Keywords
- RAS, KRAS, NRAS, BRAF, Mutated, Wee1 inhibitor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- Sep 2016
- Primary completion
- 12 Mar 2020 (actual)
- Study completion
- 12 Mar 2020 (actual)
- First posted
- 19 Sep 2016 (estimated)
- 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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AZD1775 & Irinotecan | Experimental | Drug: AZD1775, Drug: IrinotecanGroup 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (29 listed)
- 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
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 |
|---|---|---|
| AZD1775 | Drug | AZD1775 & Irinotecan |
| IrinotecanAlso: Camptosar, Campto | Drug | AZD1775 & Irinotecan |
Primary outcome
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
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2020.
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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.
Deirdre Cohen, MD principal investigator
NYU Perlmutter Cancer Center
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 AZD1775 and Irinotecan in people with Metastatic Colorectal Cancer, run by NYU Langone Health at 1 site in United States.
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 8 inclusion and 29 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: finished, as of the sponsor's last update on 12 Oct 2020. 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 United States. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
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). 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 12 Oct 2020.