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

Acacia Pharma

Status and phase: Completed; Phase 2

Conditions: CINV

Treatments: Drug: Ondansetron; Drug: APD403 IV; Drug: Dexamethasone; Drug: APD403 oral; Drug: Fosaprepitant; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01857232

DN10016

Details and patient eligibility

About

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

Enrollment: 342 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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342 participants in 5 patient groups, including a placebo group

Control

Other group

Description:

OND + DEX + FOS followed by oral DEX

Treatment:

Drug: Ondansetron

Drug: Fosaprepitant

Drug: Dexamethasone

Placebo

Placebo Comparator group

Description:

OND + APD403 followed by oral PLACEBO

Treatment:

Drug: Ondansetron

Drug: Placebo

Drug: APD403 IV

Low dose APD403

Experimental group

Description:

OND + APD403 followed by oral APD403 low dose

Treatment:

Drug: Ondansetron

Drug: APD403 IV

Drug: APD403 oral

Mid dose APD403

Experimental group

Description:

OND + APD403 followed by oral APD403 mid dose

Treatment:

Drug: Ondansetron

Drug: APD403 IV

Drug: APD403 oral

High dose APD403

Experimental group

Description:

OND + APD403 followed by oral APD403 high dose

Treatment:

Drug: Ondansetron

Drug: APD403 IV

Drug: APD403 oral