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

NCT02906059 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 14-01168
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Colorectal Cancer

Keywords

RAS; KRAS; NRAS; BRAF; Mutated; Wee1 inhibitor

Outcome Measures

Primary Outcomes (1)

• Number of participants dose limiting toxicities with treatment-related adverse events as assessed by common terminology criteria for adverse events (CTCAE), version 4.

  Up to 12 months

Secondary Outcomes (1)

• Tumor assessment by imaging techniques using Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1

  From baseline to every 8 weeks up to 12 months

Study Arms (1)

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

Drug: AZD1775; Drug: Irinotecan

Interventions

AZD1775 DRUG

AZD1775 & Irinotecan

Irinotecan DRUG

Also known as: Camptosar, Campto

AZD1775 & Irinotecan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• NYU Langone Health: lead
• AstraZeneca: collaborator

Study Sites (1)

Laura and Isaac Perlmutter Cancer Center

New York, New York, 10016, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

adavosertib; Irinotecan

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• Deirdre Cohen, MD

  NYU Perlmutter Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2016
• First Posted: September 19, 2016
• Study Start: September 1, 2016
• Primary Completion: March 12, 2020
• Study Completion: March 12, 2020
• Last Updated: October 12, 2020

Record last verified: 2020-10

Locations

US (1)