Protreat-Trial: Prophylactic Antiemetic Treatment of Opioid-induced Nausea and Vomiting (OINV) in Palliative Care

Pain is one of the most common and debilitating symptoms in patients with advanced cancer and opioids are the main stay of treatment for cancer pain. However, initiation of opioid-therapy is frequently hindered by OINV. OINV is a highly distressing symptom and can affect medication compliance, enteral absorption, and quality of life.This Phase II feasibility study is conducted to assess the feasibility of the prophylactic antiemetic treatment of OINV with palonosetron in comparison to placebo. The objective is to investigate the feasibility of patient recruitment and implementation of the study design as well as to obtain an initial estimate of the antiemetic efficacy and safety of prophylactic treatment of OINV with palonosetron compared to placebo. A total of 30 palliative patients starting an opioid-therapy (WHO II & III) for cancer pain will be randomly assigned to receive either a single dose of placebo or palonosetron. Safety and efficiency assessment are based on patient reports regarding OINV, pain and safety parameters during the following 6 days.

Inclusion criteria

• Patients aged ≥18 years
• Opioid naïve (no opioids intake within last 72 hours) patients in whom opioid therapy (WHO II & III) is started to treat cancer pain;
• Palliative (not curable) cancer pain patients;
• Patients must have a score for nausea on a 0-10 numeric rating scale (NRS) < 3 at screening visit;
• Written informed consent obtained according to international guidelines and local laws;
• Ability of patient to understand nature, importance, and individual consequences of clinical trial;
• Patients must be able to adhere to the study visit schedule and other protocol requirements.

Exclusion criteria

• Patient's death is imminent (judged by the "surprise" question of the treating physician or nurse: "Would you be surprised if this patient died within the next 7 days?"); If the answer is "no", trial subject cannot participate;
• Participation in the trial considered inappropriate based on the patient's physical, social, psychological, or spiritual condition (judgement of treating physician or nurse);
• Patients receiving antiemetic treatment within the last 72 h before study treatment period
• Patients if they are known to start a treatment causing acute nausea and/or emesis during study period
• Patients with contraindications or hypersensitivity to opioids or palonosetron, fructose, soya, lactose or peanut intolerance;
• Patients unable to take oral medications or patients receiving medication via PEG-tube;
• Patients undergoing dialyses treatment;
• Known or persistent abuse of medication, drugs, or alcohol;
• Current or planned pregnancy, nursing period;
• Patients who are sexually active and unwilling to use highly effective contraceptive methods. The following contraceptive methods with a Pearl Index lower than 1% are regarded as highly effective:

• Oral hormonal contraception ('pill')
• Dermal hormonal contraception
• Vaginal hormonal contraception (NuvaRing®)
• Contraceptive plaster
• Long-acting injectable contraceptives
• Implants that release progesterone (Implanon®)
• Tubal ligation (female sterilisation)
• Intrauterine devices that release hormones (hormone spiral)
• Double barrier methods This means that the following are not regarded as safe: condom plus spermicide, simple barrier methods (vaginal pessaries, condom, and female condoms), copper spirals, the rhythm method, basal temperature method, and the withdrawal method (coitus interruptus).

Except: Female patients who are surgically sterilised by hysterectomy or who are expected to be postmenopausal are eligible for this trial. A lack of menstruation of at least 12 months will be considered as a proof to be postmenopausal.

Men must agree to use a latex condom during sexual contact with females of childbearing potential while participating in this study even if they have undergone a successful vasectomy.

Patients must abstain from donating blood, semen, or sperm during participation in the study.

• Simultaneous participation in any other interventional clinical trial within the last 14 days before the start of this trial; simultaneous participation in registry and diagnostic trials is allowed;
• Patients without legal German language capacity who are unable to understand the nature, significance and consequences of the trial or any other co-existing medical or psychological condition that will preclude participation in the study;
• Persons who are in a relationship of dependence/employment with the sponsor or the investigator will be excluded.