Dose-finding Study of APD403 to Prevent Nausea and Vomiting After Chemotherapy

Study Overview
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Brief Summary
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Comparison of efficacy of APD403 at preventing delayed sickness in patients who have received cancer chemotherapy

Official Title
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Randomised, Double-blind, Dose-finding Phase II Study to Assess the Efficacy of APD403 in the Prevention of Nausea and Vomiting Caused by Cisplatin- or Anthracycline/Cyclophosphamide (AC)-Based Chemotherapy

Conditions
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CINV

Intervention / Treatment
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* Drug: Ondansetron
* Drug: Placebo
* Drug: Dexamethasone
* Drug: Fosaprepitant
* Drug: APD403 IV
* Drug: APD403 oral


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Male or female patients ≥ 18 years of age Ability and willingness to give written informed consent Patients scheduled to receive, on day 1 of their chemotherapy, either: (i) a first cisplatin chemotherapy infusion at a dose of ≥70 mg/m2 (males and females); or (ii) a first infusion of cyclophosphamide at a dose of 500-1500 mg/m2 in combination with either epirubicin at a dose of 60-100 mg/m2 or doxorubicin at a dose of 40-60 mg/m2 (females only) Karnofsky performance score ≥ 60% Adequate cardiac, hepatic and renal function QTc interval < 500 ms Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) < 5 x upper limit normal (ULN) Bilirubin < 5 x ULN Creatinine < 3 x ULN Adequate haematological function Haemoglobin ≥ 8 g/dL White blood count ≥ 3.0 x 109/L Platelet count ≥ 100 x 109/L For females of child-bearing potential: ability and willingness to use a highly effective form of contraception (e.g., abstinence from sexual intercourse, surgical sterilisation (of subject or partner) or a double-barrier method of contraception such as either an intra-uterine device (IUD) or an occlusive cap with spermicide, in conjunction with partner's use of a condom) during the study and for a period of at least 48 hours afterwards Exclusion Criteria Patients scheduled to receive, prior to or in the 120 hours after cisplatin or AC, any other chemotherapeutic agent with a high or moderate emetic risk Patients who have previously received anti-neoplastic chemotherapy Patients scheduled to receive paclitaxel or docetaxel during the first cycle of their chemotherapy Patients undergoing abdominal or pelvic irradiation within 48 hours prior to screening or scheduled to receive abdominal or pelvic irradiation between screening and 24 hours after cisplatin or AC administration Patients with a known prolactin-dependent tumour (e.g. pituitary gland prolactinoma or confirmed prolactin-dependent breast cancer) or phaeochromocytoma Patients with a pre-existing vestibular disorder Patients being treated with regular anti-emetic therapy including corticosteroids Patients receiving inhaled corticosteroids, unless started more than one month prior to the expected date of study entry

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Control<br>OND + DEX + FOS followed by oral DEX | Drug: Ondansetron<br>* 5HT3-antagonist<br>Drug: Dexamethasone<br>* Corticosteroid<br>Drug: Fosaprepitant<br>* NK1 antagonist<br>|
| Placebo Comparator: Placebo<br>OND + APD403 followed by oral PLACEBO | Drug: Ondansetron<br>* 5HT3-antagonist<br>Drug: Placebo<br>* Comparator<br>Drug: APD403 IV<br>* Amisulpride IV 20 mg<br>|
| Experimental: Low dose APD403<br>OND + APD403 followed by oral APD403 low dose | Drug: Ondansetron<br>* 5HT3-antagonist<br>Drug: APD403 IV<br>* Amisulpride IV 20 mg<br>Drug: APD403 oral<br>* Amisulpride oral 10, 20 or 40 mg<br>|
| Experimental: Mid dose APD403<br>OND + APD403 followed by oral APD403 mid dose | Drug: Ondansetron<br>* 5HT3-antagonist<br>Drug: APD403 IV<br>* Amisulpride IV 20 mg<br>Drug: APD403 oral<br>* Amisulpride oral 10, 20 or 40 mg<br>|
| Experimental: High dose APD403<br>OND + APD403 followed by oral APD403 high dose | Drug: Ondansetron<br>* 5HT3-antagonist<br>Drug: APD403 IV<br>* Amisulpride IV 20 mg<br>Drug: APD403 oral<br>* Amisulpride oral 10, 20 or 40 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Delayed Phase Complete Response(CR) | Delayed phase complete response (CR), defined as an absence of emetic episodes and no rescue medication use in the period from 24 to 120 hours after the initiation of chemotherapy. The primary endpoint was analysed separately in the strata of chemotherapy regimen and gender, and in the strata of country. | 24-120 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With CR in the Overall Phase. | CR defined as no emesis and no use of rescue medication, in the overall phase (0 to 120 hours after the initiation of chemotherapy) | 0 to 120 hours after the initiation of chemotherapy |