Combination of Netupitant and Palonosetron (Akynzeo®) in the Treatment of Refractory CINV
Condition: Chemotherapy Induced Nausea Vomiting
MeSH terms: Nausea; Vomiting
Intervention: Netupitant and Palonosetron
Intervention description: 300 mg of netupitant and 0.5 mg of palonosetron
Intervention MeSH terms: Palonosetron
Phase: Phase 2
Study type: Interventional
Primary purpose: Supportive Care
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Prevention and control of Chemotherapy-Induced Nausea and Vomiting (CINV) are most important
      in treatment of cancer patients. CINV is one of the most distressing severe side effects of
      cancer treatment and can have a significant impact on a patient's quality of life. The
      chemotherapy agents that cause the worst degree of nausea and vomiting are categorized into
      two groups: moderately emetogenic chemotherapy (MEC) and highly emetogenic chemotherapy
      (HEC). Nausea and vomiting that occurs within the first day of the administration of
      chemotherapy agents is considered acute CINV, while nausea and vomiting following 24 hours of
      the administration of chemotherapy agents is considered delayed CINV. Refractory CINV occurs
      when patients develop CINV during subsequent cycles of chemotherapy when drugs preventing
      vomiting and nausea (antiemetic prophylaxis) has not been successful in controlling CINV in
      earlier cycles. The purpose of this study is to assess the efficacy of Akynzeo in the
      treatment of refractory CINV
    

Eligibility criteria:

        Inclusion Criteria:

          1. Adults greater than or equal to 18 years old.

          2. Must have a histologically confirmed cancer diagnosis.

          3. Must have refractory CINV defined as nausea and/or vomiting that occurs after the
             first cycle of chemotherapy despite guideline-based prophylaxis and after first-line
             rescue medication with either a dopamine receptor antagonist, steroid, and/or
             benzodiazepine.

          4. Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.

          5. Life expectancy greater than 3 months.

          6. Corrected serum calcium level less than or equal to 10.5 mg/dL.

          7. Women of child-bearing potential must agree to use adequate contraception (hormonal or
             barrier method of birth control; abstinence) prior to study entry, for the duration of
             study participation, and for 14 days following completion of therapy.

             A) A woman of child-bearing potential is any female (regardless of sexual orientation,
             having undergone a tubal ligation, or remaining celibate by choice) who meets the
             following criteria:

             i) Has not undergone a hysterectomy or bilateral oophorectomy; or ii) Has not been
             naturally postmenopausal for at least 12 consecutive months (i.e., has not had menses
             at any time in the preceding 12 consecutive months)

          8. Women of child-bearing potential must have a negative pregnancy test prior to
             initiating study treatment.

          9. Ability to understand and willingness to sign a written informed consent.

        Exclusion Criteria:

          1. Patients with QTc interval greater than 450 ms.

          2. Patients with a known hypersensitivity reaction to 5-HT3 receptor antagonists or NK1
             receptor antagonists.

          3. Patients who have taken any medication classified as a strong CYP3A4 inducer within
             one week of Study Day 1 or 5 halflives (whichever is longer) or use of a strong or
             moderate CYP3A4 inhibitor within one week of Study Day 1 or 5 halflives (whichever is
             longer) (see Appendix 2).

          4. Patients with severe hepatic impairment as defined as AST/ALT greater than three times
             the upper limit of normal, total bilirubin greater than 3 mg/dL, and/or Child-Pugh
             score >9.

          5. Patients with end-stage renal disease defined as creatinine clearance of <15mL/min
             and/or diagnosed with Stage 5 chronic kidney disease.

          6. Pregnant or lactating females are excluded from enrollment on this trial.

          7. Patients unable to swallow oral medications. Any other condition that, in the opinion
             of the investigator, may impact the absorption of oral medications.