Clinical Trials /

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

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:



Phase 2

Trial Eligibility



  • Brief Title: Phase I/II Trial of Antagonism of HER in GI Cancer
  • 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

Clinical Trial IDs

  • ORG STUDY ID: UCL/12/0136
  • NCT ID: NCT01862003


  • Metastatic Colorectal Cancer
  • Recurrent Colorectal Cancer


AZD8931Arm 1
IrinotecanArm 1
Folinic AcidArm 1
FluorouracilArm 1
FluorouracilArm 1


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

Trial Arms

Arm 1ExperimentalAZD8931 160 mg bd, on days 1-4, + FOLFIRI in a 2 weekly schedule
  • AZD8931
  • Irinotecan
  • Folinic Acid
  • Fluorouracil
  • Fluorouracil

Eligibility Criteria

        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

          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

          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

         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

         21. Patients with hereditary fructose intolerance
Maximum Eligible Age:N/A
Minimum Eligible Age:16 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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

Secondary Outcome Measures

Measure:To evaluate the efficacy of AZD8931 plus FOLFIRI
Time Frame:Baseline to 12 weeks post treatment start
Safety Issue:
Description: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
Measure: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
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description: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.
Measure:Occurrence and Severity of Adverse Events
Time Frame:From date of registration/ randomisation until 30 days after completion of trial treatment (AZD8931 and FOLFIRI)
Safety Issue:
Description:Will include all grade 1-5 adverse events


Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:University College, London

Trial Keywords

  • Colorectal cancer
  • Metastatic Colorectal cancer
  • Recurrent Colorectal cancer
  • AZD8931
  • Chemotherapy
  • EGFR

Last Updated

August 19, 2019