Clinical trial NCT04085393: Granisetron Extended Release Injection (GERSC) for the Prevention of Chemotherapy-induced Nausea and Vomiting
Official title: Granisetron Extended Release Injection (GERSC) for the Prevention of Chemotherapy-induced Breakthrough Nausea and Vomiting (CINV) in Patients Receiving Moderately or Highly Emetogenic Chemotherapy: A Phase II Clinical Trial
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Chemotherapy-induced Nausea and Vomiting
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
Collaborators: name: Heron Therapeutics
First posted: 2019-09-11
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Chemotherapy-induced nausea and vomiting (CINV) adversely affects patients' quality of life and may affect patients' treatment decisions. The emetogenicity of the chemotherapy administered and specific patient characteristics such as female gender, age, and history of low alcohol intake can increase a patients' risk for CINV.

GERSC is a new, subcutaneously (SC) administered polymeric formulation of Granisetron that was developed to provide slow, controlled, and sustained release of Granisetron to prevent both acute and delayed CINV associated with moderately emetic chemotherapy (MEC) and highly emetic chemotherapy (HEC)

Detailed description: All patients eligible for the study receiving moderately emetogenic (MEC) chemotherapy will receive GERSC receptor antagonist on day one. All patients eligible for the study receiving highly emetogenic Chemotherapy (HEC) chemotherapy will receive GERSC receptor antagonist on day one including dexamethasone and NK-1 Receptor antagonist during cycle 1.

The primary objective is to measure the Complete Response (no emetic episodes, no use of rescue medications) in patients receiving GERSC as a replacement for the second generation 5 HT3 receptor antagonist palonosetron used in the first chemotherapy cycle for those patients receiving MEC or HEC and developed Breakthrough CINV. Complete response would be recorded specifically for the acute (0-24 hours post-chemotherapy), delayed (24-120 hours post-chemotherapy), and overall periods (0-120 hours post-chemotherapy).

This study has two study groups.

* Group 1 (HEC) will receive GERSC, dexamethasone and NK-1 antagonist prior to chemotherapy
* Group 2 (MEC) will receive GERSC and dexamethasone prior to chemotherapy

During the study:

Participants will be completing questionnaires on day 1 prior to treatment and at approximately the same time treatment was given each day for the next seven days. Participant will be assessed each day on the amount of nausea, vomiting, and/or sedation experienced in the previous 24-hour period. The assessment should take less than 5 minutes to complete each day.

Participants will be registered for Quality of Life measurement. Validated QOL measurements of fatigue and overall perception of QOL will be assessed upon registration in this study. Fatigue and overall well-being clearly can impact how well patients will do in terms of being able to tolerate and experience nausea and vomiting

Eligibility criteria: Inclusion Criteria:

* Diagnosis of malignant disease and scheduled for MEC or HEC
* Chemotherapy naive
* Age ≥18 years.
* ECOG Performance Status 0 or 1
* Required Initial Laboratory Values ≤28 days prior to registration. Patient must have adequate bone marrow, kidney, and liver function as evidenced by:
* Platelet count ≥ 100,000/ mm3
* Bilirubin ≤ 1.5 x ULN, except for subjects with Gilbert's syndrome
* Serum Creatinine ≤2.0 mg/dL
* SGOT or SGPT ≤3 x upper limit of normal (ULN)
* Absolute neutrophil count (ANC) ≥1500/mm3
* Patients receiving HEC will have received the 5HT3 receptor antagonist palonosetron, a NK-1, and dexamethasone as antiemetic prophylaxis during cycle 1 of chemotherapy
* Patients receiving MEC will have received the 5HT3 receptor antagonist palonosetron, and dexamethasone as antiemetic prophylaxis during cycle 1 of chemotherapy

Exclusion Criteria:

* No nausea or vomiting ≤ 24 hours prior to registration.
* Negative pregnancy test (serum β hCG) done ≤7 days prior to registration, for women of childbearing potential only (per clinician discretion).
* No severe cognitive compromise.
* No known history of active, untreated CNS disease (e.g. brain metastases, seizure disorder).
* No concurrent use of amifostine, thioridazine, pimozide or St. John's wort.
* No concurrent abdominal radiotherapy.
* No concurrent use of olanzapine therapy.
* No chronic alcoholism (as determined by the investigator).
* No known hypersensitivity to granisetron.
* No known uncontrolled cardiac arrhythmia or uncontrolled congestive heart failure.
* No acute myocardial infarction within the previous six months.
* No history of uncontrolled diabetes mellitus (may be on a stable dose of insulin or on a stable dose of an oral hypoglycemic agent).
* Patients with psychiatric illness that would prevent the patient from giving informed consent are not eligible for the trial
* Medical condition such as uncontrolled infection (including HIV),uncontrolled Diabetes Mellitus, unstable cardiac disease which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient are not eligible for the trial
* Patients with a "currently active" second malignancy other than non-melanoma skin cancers are not eligible for the trial; Patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for ≥ 3 years.
* Patients who cannot swallow oral formulations of the agent(s) are not eligible for the trial.

Primary outcomes:
measure: Percentage of participants with a previous history of emetic episodes
timeFrame: Baseline assessment
measure: Percentage of participants with a complete response of no emetic episode
timeFrame: Baseline through 24 hours
measure: Percentage of participants with a complete response of no emetic episode
timeFrame: Day 2 through Day 6
measure: Percentage of participants with a complete response of no emetic episode
timeFrame: Day 1 through Day 6
Secondary outcomes:
measure: Percentage of participants frequency rate of No Nausea
timeFrame: Baseline
measure: Percentage of participants frequency rate of No Nausea
timeFrame: Baseline through 24 hours
measure: Percentage of participants frequency rate of No Nausea
timeFrame: Day 2 through Day 6
measure: Percentage of participants frequency rate of No Nausea
timeFrame: Day 1 through Day 6
measure: Percentage of participants experiencing GERSC toxicity
timeFrame: Baseline through 30 days
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: The University of Alabama at Birmingham
state: Alabama
Study officials:
affiliation: University of Alabama at Birmingham
name: Rudolph M Navari, MD
role: PRINCIPAL_INVESTIGATOR
References: