We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of Irinotecan and AZD1775, a Selective Wee 1 Inhibitor, in RAS or BRAF Mutated, Second-line Metastatic Colorectal Cancer

This study is currently recruiting participants.
Verified November 2017 by New York University School of Medicine
Sponsor:
ClinicalTrials.gov Identifier:
NCT02906059
First Posted: September 19, 2016
Last Update Posted: November 22, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
New York University School of Medicine
  Purpose
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.

Condition Intervention Phase
Metastatic Colorectal Cancer Drug: AZD1775 Drug: Irinotecan Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by New York University School of Medicine:

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. [ Time Frame: Up to 12 months ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 32
Study Start Date: September 2016
Estimated Study Completion Date: September 2019
Estimated Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AZD1775 & Irinotecan

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

Drug: AZD1775 Drug: Irinotecan
Other Name: Camptosar, Campto

  Eligibility

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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
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): NCT02906059


Contacts
Contact: Deirdre Cohen, MD (212) 731-5656 Deirdre.Cohen@nyumc.org
Contact: Nida Cassim, MPH 212-263-4415 Nida.Cassim@nyumc.org

Locations
United States, New York
Laura and Isaac Perlmutter Cancer Center Recruiting
New York, New York, United States, 10016
Contact: Deirdre Cohen, MD    212-731-5656    Deirdre.Cohen@nyumc.org   
Sub-Investigator: Ping Gu, MD         
Sub-Investigator: Cynthia Leichman, MD         
Sub-Investigator: Lawrence Leichman, MD         
Sub-Investigator: Theresa Ryan, MD         
Sub-Investigator: Jennifer Wu, MD         
Sponsors and Collaborators
New York University School of Medicine
AstraZeneca
Investigators
Principal Investigator: Deirdre Cohen, MD NYU Perlmutter Cancer Center
  More Information

Responsible Party: New York University School of Medicine
ClinicalTrials.gov Identifier: NCT02906059     History of Changes
Other Study ID Numbers: 14-01168
First Submitted: September 9, 2016
First Posted: September 19, 2016
Last Update Posted: November 22, 2017
Last Verified: November 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by New York University School of Medicine:
RAS
KRAS
NRAS
BRAF
Mutated
Wee1 inhibitor

Additional relevant MeSH terms:
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
Camptothecin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action