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

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

Comparison of efficacy of APD403 at preventing delayed sickness in patients who have received cancer chemotherapy

Study Overview

• Status: Completed
• Conditions: CINV
• Intervention / Treatment: Drug: Placebo; Drug: Dexamethasone; Drug: Ondansetron; Drug: Fosaprepitant; Drug: APD403 IV; Drug: APD403 oral

• Study Type: Interventional
• Enrollment (Actual): 342
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Odense, Denmark
    • Odense University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Acacia Pharma Ltd
• Investigators: Principal Investigator: Jørn Herrstedt, MD, Odense University Hospital

Publications and helpful links

General Publications

• Herrstedt J, Summers Y, Jordan K, von Pawel J, Jakobsen AH, Ewertz M, Chan S, Naik JD, Karthaus M, Dubey S, Davis R, Fox GM. Amisulpride prevents nausea and vomiting associated with highly emetogenic chemotherapy: a randomised, double-blind, placebo-controlled, dose-ranging trial. Support Care Cancer. 2019 Jul;27(7):2699-2705. doi: 10.1007/s00520-018-4564-8. Epub 2018 Nov 28.

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (ACTUAL): February 1, 2015
• Study Completion (ACTUAL): February 1, 2015

Study Registration Dates

• First Submitted: May 16, 2013
• First Submitted That Met QC Criteria: May 17, 2013
• First Posted (ESTIMATE): May 20, 2013

Study Record Updates

• Last Update Posted (ACTUAL): November 25, 2020
• Last Update Submitted That Met QC Criteria: November 11, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dermatologic Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Serotonin Antagonists; Anti-Anxiety Agents; Antipruritics; Neurokinin-1 Receptor Antagonists; Dexamethasone; Ondansetron; Aprepitant; Fosaprepitant
• Other Study ID Numbers: DN10016