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

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ClinicalTrials.gov Identifier: NCT01862003
Recruitment Status : Completed
First Posted : May 24, 2013
Last Update Posted : August 19, 2019
Sponsor:
Collaborators:
Cancer Research UK
AstraZeneca
National Institute for Health Research, United Kingdom
Information provided by (Responsible Party):
University College, London

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.


Condition or disease Intervention/treatment Phase
Metastatic Colorectal Cancer Recurrent Colorectal Cancer Drug: AZD8931 Drug: Irinotecan Drug: Folinic Acid Drug: Fluorouracil Phase 2

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


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : May 2014
Actual Primary Completion Date : August 2, 2019
Actual Study Completion Date : August 2, 2019

Resource links provided by the National Library of Medicine


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.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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

  2. 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.

  3. 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.

  4. 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



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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01862003


Locations
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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
London, United Kingdom
The Christie NHS Foundation Trust
Manchester, United Kingdom
Sponsors and Collaborators
University College, London
Cancer Research UK
AstraZeneca
National Institute for Health Research, United Kingdom
Investigators
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Principal Investigator: Daniel Hochhauser, BA, MBBS, MRCP, D.PHIL, FRCP University College London (UCL) Cancer Institute

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Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT01862003     History of Changes
Other Study ID Numbers: UCL/12/0136
First Posted: May 24, 2013    Key Record Dates
Last Update Posted: August 19, 2019
Last Verified: August 2019

Keywords provided by University College, London:
Colorectal cancer
Metastatic Colorectal cancer
Recurrent Colorectal cancer
FOLFIRI
AZD8931
Chemotherapy
EGFR

Additional relevant MeSH terms:
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Colorectal Neoplasms
Colonic Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Leucovorin
Folic Acid
Irinotecan
Fluorouracil
Levoleucovorin
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antidotes
Protective Agents
Vitamin B Complex