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AzTrials

Metastatic Colorectal CancerPhase 2PANTHERNCT01862003

Phase I/II Trial of Antagonism of HER in GI Cancer

A Phase 2 study testing AZD8931, Irinotecan and Folinic Acid in people with Metastatic Colorectal Cancer and Recurrent Colorectal Cancer, run by University College, London at 4 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 16 years and older
What is being tested?
AZD8931, Irinotecan and Folinic Acid
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
4 sitesUnited Kingdom
Study dates
May 2014to 2 Aug 2019
Phase
Phase 2
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 16 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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
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  • 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:
  • Serum creatinine ≤1.5 x ULN
  • Calculated creatinine clearance ≥30 mL/min
  • Adequate biliary drainage (patients with stents are eligible)
  • Adequate venous access for collection of exploratory biological samples
  • 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
  • Must be able to swallow AZD8931 tablets
  • Capable of giving written informed consent
  • 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

Who cannot join

  • 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)
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  • 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)
  • Patients with chronic skin conditions e.g. acne rosacea, psoriasis, severe atopic eczema
  • 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
  • History or repeated unexplained episodes of syncope/dizziness
  • Known hypersensitivity to AZD8931, its excipients, or drugs in its class
  • 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
  • Patients with hereditary fructose intolerance

Trial locations and contacts

4 sites in 1 country.

United Kingdom4 sites

  • Barts Health NHS Trust

    London

  • Guy's and St Thomas' NHS Foundation Trust

    London

  • University College London Hospital NHS Foundation Trust

    London

  • The Christie NHS Foundation Trust

    Manchester

Other trials in United Kingdom

About this study

Official title: 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.

Read the 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

Being tested
AZD8931, Irinotecan, Folinic Acid, Fluorouracil
Keywords
Colorectal cancer, Metastatic Colorectal cancer, Recurrent Colorectal cancer, FOLFIRI, AZD8931, Chemotherapy, EGFR
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AZD8931Drug

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

  • IrinotecanDrug

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

  • Folinic AcidDrug

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

  • 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.

  • FluorouracilDrug

    2400 mg/m2 (IV) continuous infusion of Fluorouracil given over 46 hours - infusion to start after 5FU bolus.

Study groups in NCT01862003
Study groupRoleWhat they receive
Arm 1ExperimentalAZD8931 160 mg bd, on days 1-4, + FOLFIRI in a 2 weekly schedule
Receives: Drug: AZD8931; Drug: Irinotecan; Drug: Folinic Acid; Drug: Fluorouracil

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Best overall response

    Best overall response will be assessed according to RECIST v1.1.

    Measured: From registration to date of documented best response, assessed up to 36 months

Secondary outcomes (4)

  1. To evaluate the efficacy of AZD8931 plus FOLFIRI

    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

    Measured: Baseline to 12 weeks post treatment start

  2. Progression Free Survival

    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.

    Measured: 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

  3. Overall Survival

    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.

    Measured: 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)

  4. Occurrence and Severity of Adverse Events

    Will include all grade 1-5 adverse events

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 May 2013 (estimated)
  2. Study startMay 2014
  3. Primary completion2 Aug 2019
  4. Study completion2 Aug 2019

Resources

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01862003
Sponsor's protocol ID
UCL/12/0136
Acronym
PANTHER
Status last verified
Aug 2019
First submitted
7 May 2013
Last updated
19 Aug 2019
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 36352028

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing AZD8931, Irinotecan and Folinic Acid in people with Metastatic Colorectal Cancer and Recurrent Colorectal Cancer, run by University College, London at 4 sites in United Kingdom.

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 26 inclusion and 21 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 19 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United Kingdom. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

Best overall response (time frame: From registration to date of documented best response, assessed up to 36 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01862003, which also lists 1 linked publication.

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 19 Aug 2019; AzTrials last refreshed its copy on 8 Nov 2026.

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