Back to results

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

Primary Purpose

CINV

Status

Completed

Phase

Phase 2

Locations

Denmark

Study Type

Interventional

Intervention

Ondansetron

Placebo

Dexamethasone

Fosaprepitant

APD403 IV

APD403 oral

About this trial

This is an interventional prevention trial for CINV

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Odense University Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Other

Placebo Comparator

Experimental

Arm Label

Control

Placebo

Low dose APD403

Mid dose APD403

High dose APD403

Arm Description

OND + DEX + FOS followed by oral DEX

OND + APD403 followed by oral PLACEBO

OND + APD403 followed by oral APD403 low dose

OND + APD403 followed by oral APD403 mid dose

OND + APD403 followed by oral APD403 high dose

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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)

Full Information

NCT ID

NCT01857232

First Posted

May 16, 2013

Last Updated

November 11, 2020

Sponsor

Acacia Pharma Ltd

1. Study Identification

Unique Protocol Identification Number

NCT01857232

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2020

Overall Recruitment Status

Completed

Study Start Date

October 2013 (undefined)

Primary Completion Date

February 2015 (Actual)

Study Completion Date

February 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Acacia Pharma Ltd

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

CINV

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

342 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Control

Arm Type

Other

Arm Description

OND + DEX + FOS followed by oral DEX

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

OND + APD403 followed by oral PLACEBO

Arm Title

Low dose APD403

Arm Type

Experimental

Arm Description

OND + APD403 followed by oral APD403 low dose

Arm Title

Mid dose APD403

Arm Type

Experimental

Arm Description

OND + APD403 followed by oral APD403 mid dose

Arm Title

High dose APD403

Arm Type

Experimental

Arm Description

OND + APD403 followed by oral APD403 high dose

Intervention Type

Drug

Intervention Name(s)

Ondansetron

Intervention Description

5HT3-antagonist

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Comparator

Intervention Type

Drug

Intervention Name(s)

Dexamethasone

Intervention Description

Corticosteroid

Intervention Type

Drug

Intervention Name(s)

Fosaprepitant

Intervention Description

NK1 antagonist

Intervention Type

Drug

Intervention Name(s)

APD403 IV

Intervention Description

Amisulpride IV 20 mg

Intervention Type

Drug

Intervention Name(s)

APD403 oral

Intervention Description

Amisulpride oral 10, 20 or 40 mg

Primary Outcome Measure Information:

Title

Number of Participants With Delayed Phase Complete Response(CR)

Description

Time Frame

24-120 hours

Secondary Outcome Measure Information:

Title

Number of Participants With CR in the Overall Phase.

Description

CR defined as no emesis and no use of rescue medication, in the overall phase (0 to 120 hours after the initiation of chemotherapy)

Time Frame

0 to 120 hours after the initiation of chemotherapy

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jørn Herrstedt, MD

Organizational Affiliation

Odense University Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Odense University Hospital

City

Odense

Country

Denmark

12. IPD Sharing Statement

Citations:

PubMed Identifier

30488222

Citation

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.

Results Reference

derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs