Phase I/II Trial of Antagonism of HER in GI Cancer (PANTHER)

August 16, 2019 updated by: University College, London

AZD8931, an Inhibitor of EGFR, ERBB2 and ERBB3 Signalling, in Combination With FOLFIRI: a Phase I/II Study to Determine the Importance of Schedule and Activity in Colorectal Cancer

Recruitment to phase I of the PANTHER trial is complete.

Phase II, is to evaluate the best overall response rate for AZD8931 + FOLFIRI treatment.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PANTHER is a registered phase I/phase II trial in patients with recurrent or metastatic colorectal cancer.

The phase II part of the study will be a single arm trial. Patients will receive AZD8931 (an EGFR/ERBB inhibitor) in combination with FOLinic acid, Fluorouracil and IRInotecan (FOLFIRI), Treatment will be given in two-weekly cycles. Phase II's primary objective is to evaluate the Best overall response

Study Type

Interventional

Enrollment (Actual)

24

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • London, United Kingdom
        • Barts Health NHS Trust
      • London, United Kingdom
        • Guy's and St Thomas' NHS Foundation Trust
      • London, United Kingdom
        • University College London Hospital NHS Foundation Trust
      • Manchester, United Kingdom
        • The Christie NHS Foundation Trust

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Histopathological/cytological diagnosis of non-resectable, recurrent or metastatic colorectal cancer
  2. Tumour with wild-type RAS
  3. Measurable disease evaluated by RECIST criteria v1.1
  4. WHO performance status 0 or 1
  5. Age ≥ 16
  6. Estimated life expectancy > 3 months

  7. Adequate haematological function:

    • Haemoglobin ≥100 g/L
    • Absolute neutrophil count ≥1.5 x 10^9/L
    • Platelet count ≥100 x 10^9/L

  8. Adequate liver function:

    • Total bilirubin ≤1.5 x upper limit of normal (ULN) (except for patients with known documented cases of Gilbert's syndrome)
    • ALT, AST & ALP ≤2.5 x ULN in the absence of noted liver metastases
    • ALT, AST & ALP ≤5 x ULN in the presence of liver metastases

  9. Adequate renal function:

    • Serum creatinine ≤1.5 x ULN
    • Calculated creatinine clearance ≥30 mL/min
  10. Adequate biliary drainage (patients with stents are eligible)
  11. Adequate venous access for collection of exploratory biological samples
  12. Women of child-bearing potential must have a negative pregnancy test prior to study entry. Female patients and male patients with partners of child-bearing potential must agree to use an adequate contraception method, which must be continued for 6 months after completion of chemotherapy
  13. Must be able to swallow AZD8931 tablets
  14. Capable of giving written informed consent

  15. The following prior therapy is allowed:

    • Surgery - patients may have undergone a non-curative operation or palliative bypass surgery only. Patients who have previously undergone curative surgery must have evidence of non-resectable disease relapse
    • Radiotherapy - for localised disease
    • Prior adjuvant chemotherapy - provided this was completed at least 6 months before trial entry

Exclusion Criteria:

  1. Patients undergoing treatment with curative intent
  2. Any prior treatment with agents targeting the ERBB pathway
  3. Treatment with experimental drugs within 30 days or 5 half-lives of first dose of AZD8931
  4. Previous palliative chemotherapy
  5. Prior treatment with anthracyclines or mitoxantrone
  6. Current disease or condition known to interfere with absorption, distribution, metabolism or excretion of drugs (including refractory nausea and vomiting, chronic gastrointestinal disease (e.g. inflammatory bowel disease), or significant bowel resection)
  7. History of prior malignancy that will interfere with the response evaluation (exceptions listed in protocol)
  8. Evidence of severe/uncontrolled systemic diseases or laboratory finding that makes it undesirable for the patient to participate in the trial
  9. Evidence of active uncontrolled infection
  10. Patients with clinically significant ascites and/or effusions
  11. Regular use of anti-diarrhoeal
  12. Pregnant or lactating women
  13. Cardiac conditions (as detailed in the trial protocol)
  14. Any psychiatric or other disorder (e.g. brain metastases) likely to impact the ability to give informed consent
  15. Eye conditions (as detailed in the trial protocol)
  16. Patients with chronic skin conditions e.g. acne rosacea, psoriasis, severe atopic eczema
  17. Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease
  18. History or repeated unexplained episodes of syncope/dizziness
  19. Known hypersensitivity to AZD8931, its excipients, or drugs in its class
  20. The use of drugs/substances known to inhibit or induce CYP3A4 or CYP2D6, or those known to prolong QT interval, which cannot be discontinued for the duration of trial treatment
  21. Patients with hereditary fructose intolerance

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm 1
AZD8931 160 mg bd, on days 1-4, + FOLFIRI in a 2 weekly schedule
Drug: AZD8931
160 mg AZD8931 tablets, twice daily on days 1 - 4 of each 2-weekly cycle
Drug: Irinotecan
180 mg/m2 (IV infusion) of Irinotecan on day 1 of each 2-weekly cycle - can be given simultaneously with Folinic acid.
Drug: Folinic Acid
350 mg (IV infusion) of Folinic acid on day 1 of each 2-weekly cycle - can be given simultaneously with Irinotecan.
Drug: Fluorouracil
400 mg/m2 (IV bolus) of Fluorouracil on day 1 of each 2-weekly cycle, to be given after completion of Irinotecan and Folinic acid.
Drug: Fluorouracil
2400 mg/m2 (IV) continuous infusion of Fluorouracil given over 46 hours - infusion to start after 5FU bolus.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Best overall response
Time Frame: From registration to date of documented best response, assessed up to 36 months
Best overall response will be assessed according to RECIST v1.1.
From registration to date of documented best response, assessed up to 36 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To evaluate the efficacy of AZD8931 plus FOLFIRI
Time Frame: Baseline to 12 weeks post treatment start
Percentage change in tumour size will be considered the best response only if a second assessment has been carried out which confirms SD at least four weeks after trial entry. Assessment will be determined using CT scans performed at baseline, 12 weeks after start of chemotherapy, then every 3 months until disease progression up to 3 years from registration/ randomisation
Baseline to 12 weeks post treatment start
Progression Free Survival
Time Frame: From date of randomisation to date of documented disease progression or death from any cause, whichever comes first, assessed up to 3 years from date of registration/ randomisation
Progression-free survival time will be calculated from the date of trial entry to the date of documented progression, or death from any cause. In cases where progression is suspected and subsequently confirmed by scans, the date of documented suspected progression will be used.
From date of randomisation to date of documented disease progression or death from any cause, whichever comes first, assessed up to 3 years from date of registration/ randomisation
Overall Survival
Time Frame: From date of registration/ randomisation until date of death or date of last follow-up assessment (up to 3 years from date of registration/ randomisation)
Overall survival time will be calculated from the date of trial entry to the date of death from any cause or end of trial follow-up.
From date of registration/ randomisation until date of death or date of last follow-up assessment (up to 3 years from date of registration/ randomisation)
Occurrence and Severity of Adverse Events
Time Frame: From date of registration/ randomisation until 30 days after completion of trial treatment (AZD8931 and FOLFIRI)
Will include all grade 1-5 adverse events
From date of registration/ randomisation until 30 days after completion of trial treatment (AZD8931 and FOLFIRI)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University College, London

Collaborators

AstraZeneca
Cancer Research UK
National Institute for Health Research, United Kingdom

Investigators

  • Principal Investigator: Daniel Hochhauser, BA, MBBS, MRCP, D.PHIL, FRCP, University College London (UCL) Cancer Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2014

Primary Completion (Actual)

August 2, 2019

Study Completion (Actual)

August 2, 2019

Study Registration Dates

First Submitted

May 7, 2013

First Submitted That Met QC Criteria

May 21, 2013

First Posted (Estimate)

May 24, 2013

Study Record Updates

Last Update Posted (Actual)

August 19, 2019

Last Update Submitted That Met QC Criteria

August 16, 2019

Last Verified

August 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UCL/12/0136

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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