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Fosaprepitant + 5HT3 Receptor Antagonists + Dexamethasone in Germ Cell Tumors

Primary Purpose

Chemotherapy-Induced Nausea and Vomiting

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Fosaprepitant

Dexamethasone

5HT3

About this trial

This is an interventional treatment trial for Chemotherapy-Induced Nausea and Vomiting focused on measuring Fosaprepitant, 5HT3 Receptor Antagonists, Dexamethasone, Germ Cell Tumors, Testis Cancer, Rescue Medications

Eligibility Criteria

15 Years - undefined (Child, Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

Male patients ≥15 years of age with histologically or cytologically confirmed diagnosis of germ cell tumor receiving a standard 5 day cisplatin based chemotherapy regimen. Prior chemotherapy is allowed. Patients do not have to be chemo naïve.
Written informed consent and HIPAA authorization for release of personal health information.
Patients must have had no nausea or vomiting for 24 hours and no anti-emetic use for 72 hours prior to starting protocol therapy. Treatment must not start in registered patients until this criteria is met.

Exclusion Criteria:

No active central nervous system (CNS) metastases. Patients with neurological symptoms must undergo a head CT scan or brain MRI to exclude brain metastasis. NOTE: A patient with prior brain metastasis may be considered if they have completed their treatment for brain metastasis, no longer require corticosteroids, and are asymptomatic.
No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, Gleason < grade 7 prostate cancers, or other cancer for which the patient has been disease-free for at least 1 year.
No previous treatment with any investigational agent within 30 days prior to registration for protocol therapy.
No concurrent participation in a clinical trial which involves another investigational agent.
No use of agents expected to induce the metabolism of fosaprepitant which include: rifampin, rifabutin, phenytoin, carbamazepine, and barbiturates.
No concurrent use of agents which may inhibit metabolism of fosaprepitant which include: cisapride, macrolide antibiotics (erythromycin, clarithromycin, azithromycin), azole antifungal agents (ketoconazole, itraconazole, voriconazole, fluconazole), amifostine, nelfinavir, calcium channel antagonists such as verapamil and diltiazem, and ritonavir.
No concurrent use of warfarin while on study.
No known history of anticipatory nausea or vomiting.
No clinically significant infections as judged by the treating investigator.

Sites / Locations

Indiana University Melvin and Bren Simon Cancer Center
Siteman Cancer Center
Nebraska Cancer Specialists
MUSC Hollings Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Fosaprepitant + 5HT3 Receptor Antagonists + Dexamethasone

Arm Description

Patients must have no nausea and/or vomiting for 24 hours and must not have used other anti-emetics for 72 hours prior to starting protocol treatment. Treatment must not start until this criteria is satisfied. Any germ cell chemotherapy regimen utilizing Cisplatin (20mg/m2 x 5 days). Acute emesis prophylaxis: Any 5HT3 receptor antagonist may be used D1 - 5 or D1, 3 and 5 if palonosetron is used per institutional standards. Dexamethasone 20mg PO (orally) daily, D1 and 2 Fosaprepitant 150mg IV on day 3 Delayed emesis prophylaxis: Fosaprepitant 150mg IV on D5 Dexamethasone 4mg PO BID (twice a day) on D6, 7 and 8 PRN antiemetics allowed at the discretion of the treating investigator No additional doses of 5HT3 receptor antagonist, dexamethasone, or fosaprepitant will be given during the acute or delayed treatment periods

Outcomes

Primary Outcome Measures

Percentage of Participants With Complete Response of Acute and Delayed Chemotherapy Induced Nausea and Vomiting

complete response (CR) of both acute (days 1 through 5) and delayed (days 6 through 8) CINV, defined by no emetic episodes or use of rescue medications

Secondary Outcome Measures

Total Number of Emetic Episodes

total number of emetic episodes

Use of Rescue Medications.

Total number of patients who received rescue medications.

Self-Reported Assessment of Nausea

the patient's self-reported assessment of nausea Days 1-8 using a 0-100mm visual analog scale (VAS) median. The Visual Analouge (VAS) 100mm Scale Score for Chemotherapy Induced Nausea and Vomiting (CINV). Participants were asked to mark a linear scale 100mm in length representing their level of nausea with 0mm indicating no nausea and 100mm indicating severe nausea. Median VAS scores (in mm) are reported, per day.

Full Information

NCT ID

NCT01736917

First Posted

November 21, 2012

Last Updated

April 18, 2016

Sponsor

Lawrence Einhorn

Collaborators

Hoosier Cancer Research Network, Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT01736917

Brief Title

Fosaprepitant + 5HT3 Receptor Antagonists + Dexamethasone in Germ Cell Tumors

Official Title

Phase II Study of Fosaprepitant + 5HT3 Receptor Antagonists + Dexamethasone in Patients With Germ Cell Tumors Undergoing 5 Day Cisplatin-based Chemotherapy: Hoosier Oncology Group Study QL12-153

Study Type

Interventional

2. Study Status

Record Verification Date

April 2016

Overall Recruitment Status

Completed

Study Start Date

January 2013 (undefined)

Primary Completion Date

March 2015 (Actual)

Study Completion Date

June 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Lawrence Einhorn

Collaborators

Hoosier Cancer Research Network, Merck Sharp & Dohme LLC

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The hypothesis is that the substitution of multi-day oral aprepitant with (intravenous) IV fosaprepitant, in combination with a 5-HT3 receptor antagonists (5HT3RA) + dexamethasone will provide comparable protection from 5 day cisplatin chemotherapy induced nausea and vomiting, compared to the results of our prior study of aprepitant. This study will be the first clinical trial evaluating fosaprepitant in patients receiving multi-day cisplatin. This will be a single arm, phase II study. The investigators propose to utilize intravenous (IV) fosaprepitant on days 3 and 5 of the 5-day cisplatin chemotherapy regimen. It is anticipated that fosaprepitant can suppress delayed chemo-induced nausea and vomiting for 2-5 days after therapy. This study will test the value of fosaprepitant in this patient population.

Detailed Description

OUTLINE: This is a multi-center study. Treatment Regimen: Patients must have no nausea and/or vomiting for 24 hours and must not have used other anti-emetics for 72 hours prior to starting protocol treatment. Treatment must not start until this criteria is satisfied. Any germ cell chemotherapy regimen utilizing cisplatin (20mg/m^2 x 5 days). This will usually be combined with bleomycin (BEP), etoposide (EP), ifosfamide (VIP), vinblastine (VeIP), paclitaxel (TIP) or epirubicin. All of these regimens get the identical cisplatin, which is the only highly emetic drug in any of the chemo regimens. Acute emesis prophylaxis (administered per institutional standards prior to chemotherapy): Any 5HT3 receptor antagonist may be used days 1 through 5 or days 1, 3 and 5 if palonosetron is used per institutional standards. Dexamethasone 20mg PO (orally) daily, days 1 and 2 Fosaprepitant 150mg IV on day 3 Delayed emesis prophylaxis: Fosaprepitant 150mg IV on day 5 Dexamethasone 4mg PO BID (twice a day) on days 6, 7 and 8 PRN (as needed) antiemetics allowed at the discretion of the treating investigator No additional doses of 5HT3 receptor antagonist, dexamethasone, or fosaprepitant will be given during the acute or delayed treatment periods ECOG Performance Status of 0-2 Life Expectancy: Not specified Hematopoietic: White blood cell count (WBC) > 3.0 K/mm3 Absolute neutrophil count ≥ 1.5 K/mm3 Hemoglobin (Hgb) > 10 g/dL Platelets > 100 K/mm3 Hepatic: Bilirubin < 1.5 x ULN (upper limit of normal) Aspartate aminotransferase (AST, SGOT) ≤ 3 x ULN Alanine aminotransferase (ALT, SGPT) ≤ 3 x ULN Renal: Creatinine ≤ 2 mg/dl

6. Conditions and Keywords

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

Chemotherapy-Induced Nausea and Vomiting

Keywords

Fosaprepitant, 5HT3 Receptor Antagonists, Dexamethasone, Germ Cell Tumors, Testis Cancer, Rescue Medications

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

65 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Fosaprepitant + 5HT3 Receptor Antagonists + Dexamethasone

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Fosaprepitant

Intervention Description

Fosaprepitant 150mg IV D3 for acute prophylaxis Fosaprepitant 150mg IV on Day 5 for delayed prophylaxis

Intervention Type

Drug

Intervention Name(s)

Dexamethasone

Intervention Description

Dexamethasone 20mg PO daily on D1 and 2 for acute prophylaxis Dexamethasone 4mg PO BID on Days 6 through 8

Intervention Type

Drug

Intervention Name(s)

5HT3

Intervention Description

Any 5HT3RA on D1-5; D1, 3 and 5 if palonosetron is used.

Primary Outcome Measure Information:

Title

Percentage of Participants With Complete Response of Acute and Delayed Chemotherapy Induced Nausea and Vomiting

Description

complete response (CR) of both acute (days 1 through 5) and delayed (days 6 through 8) CINV, defined by no emetic episodes or use of rescue medications

Time Frame

Days 1-8 of chemotherapy regimen

Secondary Outcome Measure Information:

Title

Total Number of Emetic Episodes

Description

total number of emetic episodes

Time Frame

Days 1-8 of chemotherapy regimen

Title

Use of Rescue Medications.

Description

Total number of patients who received rescue medications.

Time Frame

Days 1-8 of chemotherapy regimen

Title

Self-Reported Assessment of Nausea

Description

Time Frame

Days 1-8 of chemotherapy regimen

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

15 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male patients ≥15 years of age with histologically or cytologically confirmed diagnosis of germ cell tumor receiving a standard 5 day cisplatin based chemotherapy regimen. Prior chemotherapy is allowed. Patients do not have to be chemo naïve. Written informed consent and HIPAA authorization for release of personal health information. Patients must have had no nausea or vomiting for 24 hours and no anti-emetic use for 72 hours prior to starting protocol therapy. Treatment must not start in registered patients until this criteria is met. Exclusion Criteria: No active central nervous system (CNS) metastases. Patients with neurological symptoms must undergo a head CT scan or brain MRI to exclude brain metastasis. NOTE: A patient with prior brain metastasis may be considered if they have completed their treatment for brain metastasis, no longer require corticosteroids, and are asymptomatic. No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, Gleason < grade 7 prostate cancers, or other cancer for which the patient has been disease-free for at least 1 year. No previous treatment with any investigational agent within 30 days prior to registration for protocol therapy. No concurrent participation in a clinical trial which involves another investigational agent. No use of agents expected to induce the metabolism of fosaprepitant which include: rifampin, rifabutin, phenytoin, carbamazepine, and barbiturates. No concurrent use of agents which may inhibit metabolism of fosaprepitant which include: cisapride, macrolide antibiotics (erythromycin, clarithromycin, azithromycin), azole antifungal agents (ketoconazole, itraconazole, voriconazole, fluconazole), amifostine, nelfinavir, calcium channel antagonists such as verapamil and diltiazem, and ritonavir. No concurrent use of warfarin while on study. No known history of anticipatory nausea or vomiting. No clinically significant infections as judged by the treating investigator.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Lawrence Einhorn, M.D.

Organizational Affiliation

Hoosier Cancer Research Network

Official's Role

Study Chair

Facility Information:

Facility Name

Indiana University Melvin and Bren Simon Cancer Center

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46202

Country

United States

Facility Name

Siteman Cancer Center

City

St. Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

Facility Name

Nebraska Cancer Specialists

City

Omaha

State/Province

Nebraska

ZIP/Postal Code

68114

Country

United States

Facility Name

MUSC Hollings Cancer Center

City

Charleston

State/Province

South Carolina

ZIP/Postal Code

29425

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

Citation

Costantine Albany, Nasser H. Hanna, Joel Picus, Ralph J. Hauke, Christopher A. Fausel, Ziyue Liu, Mary J. Brames, Lawrence H. Einhorn. Phase II study of fosaprepitant plus 5HT3 receptor antagonists plus dexamethasone in patients with germ cell tumors undergoing 5-day cisplatin-based chemotherapy: Hoosier Oncology Group QL12-153. J Clin Oncol 32:5s, 2014 (suppl; abstr TPS4594)

Results Reference

background

Citation

Brames MJ, Case-Eads S, Hanna NH, Fausel CA, Breen T, Einhorn LH. Phase II study of fosaprepitant +5HT3 receptor antagonist + dexamethasone in patients with germ cell tumors undergoing 5-day cisplatin-based chemotherapy: A Hoosier Cancer Research Network Study. J Clin Oncol 33:5s, 2015 (suppl; abstr e20737)

Results Reference

result

PubMed Identifier

26838019

Citation

Adra N, Albany C, Brames MJ, Case-Eads S, Johnson CS, Liu Z, Fausel CA, Breen T, Hanna NH, Hauke RJ, Picus J, Einhorn LH. Phase II study of fosaprepitant + 5HT3 receptor antagonist + dexamethasone in patients with germ cell tumors undergoing 5-day cisplatin-based chemotherapy: a Hoosier Cancer Research Network study. Support Care Cancer. 2016 Jul;24(7):2837-42. doi: 10.1007/s00520-016-3100-y. Epub 2016 Feb 2.

Results Reference

derived

Links:

URL

http://www.hoosiercancer.org

Description

Hoosier Cancer Research Network Website

Learn more about this trial

Fosaprepitant + 5HT3 Receptor Antagonists + Dexamethasone in Germ Cell Tumors

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