NCT01862003

Brief Summary

Recruitment to phase I of the PANTHER trial is complete. Phase II, is to evaluate the best overall response rate for AZD8931 + FOLFIRI treatment.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
24

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started May 2014

Longer than P75 for phase_2

Geographic Reach
1 country

4 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 7, 2013

Completed
17 days until next milestone

First Posted

Study publicly available on registry

May 24, 2013

Completed
11 months until next milestone

Study Start

First participant enrolled

May 1, 2014

Completed
5.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 2, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 2, 2019

Completed
Last Updated

August 19, 2019

Status Verified

August 1, 2019

Enrollment Period

5.3 years

First QC Date

May 7, 2013

Last Update Submit

August 16, 2019

Conditions

Metastatic Colorectal CancerRecurrent Colorectal Cancer

Keywords

Colorectal cancerMetastatic Colorectal cancerRecurrent Colorectal cancerFOLFIRIAZD8931ChemotherapyEGFR

Outcome Measures

Primary Outcomes (1)

  • Best overall response

    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 Outcomes (4)

  • To evaluate the efficacy of AZD8931 plus FOLFIRI

    Baseline to 12 weeks post treatment start

  • Progression Free Survival

    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

    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

    From date of registration/ randomisation until 30 days after completion of trial treatment (AZD8931 and FOLFIRI)

Study Arms (1)

Arm 1

EXPERIMENTAL

AZD8931 160 mg bd, on days 1-4, + FOLFIRI in a 2 weekly schedule

Drug: AZD8931Drug: IrinotecanDrug: Folinic AcidDrug: Fluorouracil

Interventions

AZD8931DRUG

160 mg AZD8931 tablets, twice daily on days 1 - 4 of each 2-weekly cycle

Arm 1
IrinotecanDRUG

180 mg/m2 (IV infusion) of Irinotecan on day 1 of each 2-weekly cycle - can be given simultaneously with Folinic acid.

Arm 1
Folinic AcidDRUG

350 mg (IV infusion) of Folinic acid on day 1 of each 2-weekly cycle - can be given simultaneously with Irinotecan.

Arm 1
FluorouracilDRUG

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.

Arm 1

Eligibility Criteria

Age16 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Histopathological/cytological diagnosis of non-resectable, recurrent or metastatic colorectal cancer
  • Tumour with wild-type RAS
  • Measurable disease evaluated by RECIST criteria v1.1
  • WHO performance status 0 or 1
  • Age ≥ 16
  • Estimated life expectancy \> 3 months
  • Adequate haematological function:
  • Haemoglobin ≥100 g/L
  • Absolute neutrophil count ≥1.5 x 10\^9/L
  • Platelet count ≥100 x 10\^9/L
  • 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
  • Adequate renal function:
  • +11 more criteria

You may not qualify if:

  • Patients undergoing treatment with curative intent
  • Any prior treatment with agents targeting the ERBB pathway
  • Treatment with experimental drugs within 30 days or 5 half-lives of first dose of AZD8931
  • Previous palliative chemotherapy
  • Prior treatment with anthracyclines or mitoxantrone
  • 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)
  • History of prior malignancy that will interfere with the response evaluation (exceptions listed in protocol)
  • Evidence of severe/uncontrolled systemic diseases or laboratory finding that makes it undesirable for the patient to participate in the trial
  • Evidence of active uncontrolled infection
  • Patients with clinically significant ascites and/or effusions
  • Regular use of anti-diarrhoeal
  • Pregnant or lactating women
  • Cardiac conditions (as detailed in the trial protocol)
  • Any psychiatric or other disorder (e.g. brain metastases) likely to impact the ability to give informed consent
  • Eye conditions (as detailed in the trial protocol)
  • +6 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Barts Health NHS Trust

London, United Kingdom

Location

Guy's and St Thomas' NHS Foundation Trust

London, United Kingdom

Location

University College London Hospital NHS Foundation Trust

London, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, United Kingdom

Location

Related Publications (1)

  • Propper DJ, Gao F, Saunders MP, Sarker D, Hartley JA, Spanswick VJ, Lowe HL, Hackett LD, Ng TT, Barber PR, Weitsman GE, Pearce S, White L, Lopes A, Forsyth S, Hochhauser D. PANTHER: AZD8931, inhibitor of EGFR, ERBB2 and ERBB3 signalling, combined with FOLFIRI: a Phase I/II study to determine the importance of schedule and activity in colorectal cancer. Br J Cancer. 2023 Jan;128(2):245-254. doi: 10.1038/s41416-022-02015-x. Epub 2022 Nov 9.

    PMID: 36352028DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

AZD 8931IrinotecanLeucovorinFluorouracil

Condition Hierarchy (Ancestors)

Intestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal Diseases

Intervention Hierarchy (Ancestors)

CamptothecinAlkaloidsHeterocyclic CompoundsFormyltetrahydrofolatesTetrahydrofolatesFolic AcidPterinsPteridinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingCoenzymesEnzymes and CoenzymesUracilPyrimidinonesPyrimidinesHeterocyclic Compounds, 1-Ring

Study Officials

  • Daniel Hochhauser, BA, MBBS, MRCP, D.PHIL, FRCP

    University College London (UCL) Cancer Institute

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 7, 2013

First Posted

May 24, 2013

Study Start

May 1, 2014

Primary Completion

August 2, 2019

Study Completion

August 2, 2019

Last Updated

August 19, 2019

Record last verified: 2019-08

Locations

GB(4)