Granisetron, Aprepitant, and Dexamethasone in Preventing Nausea and Vomiting in Patients Receiving Chemotherapy for Stage II, III, or IV Ovarian Cancer

• Sponsor: Gynecologic Oncology Group (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01275664
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 4
• Locations: 2
• Arm: 1
• Patients Per Site: 2

Study Details

Study Description

Brief Summary

This clinical trial is studying how well granisetron, aprepitant, and dexamethasone work in preventing nausea and vomiting in patients receiving chemotherapy for stage II, stage III, or stage IV ovarian cancer. Granisetron patch, aprepitant and dexamethasone may help lessen or prevent nausea and vomiting in patients receiving chemotherapy for stage II, stage III, or stage IV ovarian cancer.

Condition or Disease	Intervention/Treatment	Phase
Nausea and Vomiting; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Cystadenocarcinoma; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Undifferentiated Ovarian Carcinoma	Procedure: Adjuvant Therapy; Drug: Aprepitant; Drug: Carboplatin; Drug: Cisplatin; Drug: Dexamethasone; Drug: Granisetron Transdermal Patch; Procedure: Management of Therapy Complications; Other: Questionnaire Administration	N/A

Detailed Description

PRIMARY OBJECTIVES:

1. To determine the frequency of chemotherapy-induced nausea and vomiting based on complete response (no vomiting and no use of rescue therapy) during the 6 days following intraperitoneal (IP) chemotherapy for the 3-day regimen of aprepitant (both injection and capsules) in combination with granisetron transdermal system and dexamethasone in ovarian cancer patients receiving IP cisplatin OR IP carboplatin.

SECONDARY OBJECTIVES:

1. To evaluate possible endpoints for the chemotherapy-induced nausea and vomiting, including:

• Functional Living Index-Emesis (FLIE) questionnaire scores

• Mean vomiting, nausea and total FLIE scores and changes from baseline in FLIE scores

• Percentages of patients with no impact on daily living (NIDL), i.e. > 108/126 total FLIE score II. To describe the timing of nausea and vomiting that may guide modifications to the standard regimen.

OUTLINE: This is a multicenter study.

Patients apply one patch of granisetron transdermal system to the upper outer arm on day 0 (at least 24 hours before intraperitoneal [IP] platinum therapy). Patients then receive dexamethasone orally (PO) on days 1-4, aprepitant IV over 15 minutes on day 1 (30 minutes before IP platinum therapy), and aprepitant PO on days 2-3.

Patients complete the Functional Living Index--Emesis (FLIE) and a symptom diary at baseline and on days 3 and 6.

Study Design

• Study Type: Interventional
• Actual Enrollment: 4 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: Pilot Study of Standard Therapy for Prevention of Nausea and Emesis Associated With First Line Post-Operative Intraperitoneal Chemotherapy
• Study Start Date: Jun 1, 2011
• Actual Primary Completion Date: May 1, 2014

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (granisetron, dexamethasone, aprepitant) Patients apply one patch of granisetron transdermal system to the upper outer arm on day 0 (at least 24 hours before intraperitoneal [IP] platinum therapy). Patients then receive dexamethasone PO on days 1-4, aprepitant IV over 15 minutes on day 1 (30 minutes before IP platinum therapy), and aprepitant PO on days 2-3.

Procedure: Adjuvant Therapy; Ancillary studies; Other Names: adjunct therapy adjunctive therapy ; Drug: Aprepitant; Given IV and PO; Other Names: Emend L-754030 MK-0869 ONO-7436 ; Drug: Carboplatin; Given IP; Other Names: Blastocarb Carboplat Carboplatin Hexal Carboplatino Carbosin Carbosol Carbotec CBDCA Displata Ercar JM-8 Nealorin Novoplatinum Paraplat Paraplatin Paraplatin AQ Paraplatine Platinwas Ribocarbo ; Drug: Cisplatin; Given IP; Other Names: Abiplatin Blastolem Briplatin CDDP Cis-diammine-dichloroplatinum Cis-diamminedichloridoplatinum Cis-diamminedichloro Platinum (II) Cis-diamminedichloroplatinum Cis-dichloroammine Platinum (II) Cis-platinous Diamine Dichloride Cis-platinum Cis-platinum II Cis-platinum II Diamine Dichloride Cismaplat Cisplatina Cisplatinum Cisplatyl Citoplatino Citosin Cysplatyna DDP Lederplatin Metaplatin Neoplatin Peyrone's Chloride Peyrone's Salt Placis Plastistil Platamine Platiblastin Platiblastin-S Platinex Platinol Platinol- AQ Platinol-AQ Platinol-AQ VHA Plus Platinoxan Platinum Platinum Diamminodichloride Platiran Platistin Platosin ; Drug: Dexamethasone; Given PO; Other Names: Aacidexam Adexone Aknichthol Dexa Alba-Dex Alin Alin Depot Alin Oftalmico Amplidermis Anemul mono Auricularum Auxiloson Baycuten Baycuten N Cortidexason Cortisumman Decacort Decadrol Decadron Decalix Decameth Decasone R.p. Dectancyl Dekacort Deltafluorene Deronil Desamethasone Desameton Dexa-Mamallet Dexa-Rhinosan Dexa-Scheroson Dexa-sine Dexacortal Dexacortin Dexafarma Dexafluorene Dexalocal Dexamecortin Dexameth Dexamethasonum Dexamonozon Dexapos Dexinoral Dexone Dinormon Fluorodelta Fortecortin Gammacorten Hexadecadrol Hexadrol Lokalison-F Loverine Methylfluorprednisolone Millicorten Mymethasone Orgadrone Spersadex Visumetazone ; Drug: Granisetron Transdermal Patch; Apply one patch to upper arm; Other Names: Granisetron Transdermal System Sancuso ; Procedure: Management of Therapy Complications; Ancillary studies; Other: Questionnaire Administration; Ancillary studies

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Complete Control Defined as no Vomiting and no Use of Rescue Medications (for Nausea or Emesis) [During the 6 days following chemotherapy]

   Number of participants who had complete control defined by no vomiting

Secondary Outcome Measures

1. Change in Vomiting, Nausea and Total FLIE Scores [Baseline to day 6]

2. Frequency of Adverse Effects as Assessed by the NCI CTCAE v 4.0 [Up to day 6]

   Adverse events at least possibly related to treatment

3. Mean and Standard Deviation of Vomiting, Nausea, and Total FLIE Scores [Baseline]

4. Percentages of Patients With NIDL Based on FLIE [Up to day 6]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of ovarian epithelial, fallopian tube, or primary peritoneal carcinoma

• Stage II, III, or IV disease with optimal (=< 1 cm residual disease) or suboptimal residual disease

• All patients must have a procedure for determining diagnosis of epithelial ovarian, fallopian tube, primary peritoneal, with appropriate tissue for histologic evaluation

• The minimum surgery required is an abdominal surgery providing tissue for histologic evaluation and establishing and documenting the primary site and stage, as well as a maximal effort at tumor debulking; if additional surgery was performed, it should have been in accordance with appropriate surgery for ovarian or peritoneal carcinoma described in the Gynecologic Oncology Group (GOG) Surgical Procedures Manual

• Patients with the following histologic epithelial cell types are eligible:

• Serous adenocarcinoma, endometrioid adenocarcinoma, mucinous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, transitional cell carcinoma, malignant Brenner's Tumor, or adenocarcinoma not otherwise specified (N.O.S.)

• However, the histologic features of the tumor must be compatible with a primary Müllerian epithelial adenocarcinoma; if doubt exists, it is recommended that the investigator should have the slides reviewed by an independent pathologist prior to entry

• Patients may have co-existing endometrial cancer so long as the primary origin of invasive tumor is ovarian or peritoneal for clarification of synchronous primary endometrial cancer

• Patients receiving the initial course of chemotherapy including

• Paclitaxel 135 mg/M2 IV over 3 hours on day 1 and

• Cisplatin 75 mg/M2 IP on day 2 OR

• Paclitaxel 80 mg/m2 IV days 1, 8 and 15 and

• Carboplatin AUC 6 IP on day 1

• Prothrombin time (PT) such that international normalized ratio (INR) is < 1.5 x ULN (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin)

• Partial thromboplastin time (PTT) < 1.5 times the upper limit of normal (heparin, lovenox or alternative anticoagulants are acceptable)

• Patients with a GOG Performance Status of 0, 1, or 2

• Patients who are able to read, understand and write English; if FLIE which has been translated into other languages, and validated, becomes available, then patients speaking these languages can be enrolled if translation of the symptom diary can be arranged dependent on availability of suitable translators

• Patients who are able to complete the assessments

• Patients who are able to comply with the anti-emetic therapy

• Patients must have met pre-entry requirements

• Patients must have signed an approved informed consent and authorization permitting release of personal health information

Exclusion Criteria:

• Patients who are known to be hypersensitive to aprepitant, granisetron or any of the components of the patch or to dexamethasone

• Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis are excluded; prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease

• Patients who have received prior chemotherapy for any abdominal or pelvic tumor including neo-adjuvant chemotherapy for their ovarian or primary peritoneal cancer are excluded; patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease

• Patients who are pregnant or nursing; to date, no fetal studies in animals or humans have been performed; the possibility of harm to a fetus is likely

• Patients with clinical symptoms or signs of gastrointestinal obstruction and/ or those who require parenteral hydration and/or nutrition; patients with history or current diagnosis of inflammatory bowel disease are not eligible

• Patients with medical history or conditions not otherwise previously specified which in the opinion of the investigator should exclude participation in this study; examples of this would be hearing loss or neuropathy which would prevent tolerance to cisplatin, and paclitaxel administration; the investigator should feel free to consult the Study Chair or Study Co-Chairs for uncertainty in this regard

• Patients who, in the opinion of the treating physician, have a medical condition, or currently take medications, which are felt to contraindicate safe or effective administration of the standard three drug anti-emetic regimen used in this study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sudarshan K Sharma MD Limted-Gynecologic Oncology	Hinsdale	Illinois	United States	60521
2	Women and Infants Hospital	Providence	Rhode Island	United States	02905

Sponsors and Collaborators

• Gynecologic Oncology Group
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Steven Plaxe, NRG Oncology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gynecologic Oncology Group
• ClinicalTrials.gov Identifier: NCT01275664
• Other Study ID Numbers: GOG-0272; NCI-2011-02660; CDR0000692516; GOG-0272; GOG-0272; GOG-0272; U10CA101165
• First Posted: Jan 12, 2011
• Last Update Posted: May 22, 2018
• Last Verified: May 1, 2017

• Additional relevant MeSH terms: Carcinoma; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Fallopian Tube Neoplasms; Peritoneal Neoplasms; Carcinoma, Endometrioid; Cystadenocarcinoma; Cystadenocarcinoma, Serous; Cystadenocarcinoma, Mucinous; Brenner Tumor; Nausea; Vomiting; Dexamethasone; Dexamethasone acetate; Cisplatin; Carboplatin; Aprepitant; Granisetron; Ichthammol; BB 1101

Study Results

Participant Flow

Recruitment Details	This trial was opened to patient entry on June 13, 2011 and was closed to accrual on December 12, 2011. The trial closed early because enrollment into this study was dependent on accruing patients simultaneously with GOG 252 (NCT00951496). When GOG 252 closed, there was no patient population to recruit from for this study.

Arm/Group Title	Treatment (Granisetron, Dexamethasone, Aprepitant)
Arm/Group Description	Patients apply one patch of granisetron transdermal system to the upper outer arm on day 0 (at least 24 hours before intraperitoneal [IP] platinum therapy). Patients then receive dexamethasone PO on days 1-4, aprepitant IV over 15 minutes on day 1 (30 minutes before IP platinum therapy), and aprepitant PO on days 2-3. Adjuvant Therapy: Ancillary studies Aprepitant: Given IV and PO Carboplatin: Given IP Cisplatin: Given IP Dexamethasone: Given PO Granisetron Transdermal Patch: Apply one patch to upper arm Management of Therapy Complications: Ancillary studies Questionnaire Administration: Ancillary studies
Period Title: Overall Study
STARTED	4
COMPLETED	4
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment (Granisetron, Dexamethasone, Aprepitant)
Arm/Group Description	Patients apply one patch of granisetron transdermal system to the upper outer arm on day 0 (at least 24 hours before intraperitoneal [IP] platinum therapy). Patients then receive dexamethasone PO on days 1-4, aprepitant IV over 15 minutes on day 1 (30 minutes before IP platinum therapy), and aprepitant PO on days 2-3. Adjuvant Therapy: Ancillary studies Aprepitant: Given IV and PO Carboplatin: Given IP Cisplatin: Given IP Dexamethasone: Given PO Granisetron Transdermal Patch: Apply one patch to upper arm Management of Therapy Complications: Ancillary studies Questionnaire Administration: Ancillary studies
Overall Participants	4
Age, Customized (Count of Participants)
40-49 years	0 0%
50-59 years	1 25%
60-69 years	2 50%
70-79 years	1 25%
Sex: Female, Male (Count of Participants)
Female	4 100%
Male	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Complete Control Defined as no Vomiting and no Use of Rescue Medications (for Nausea or Emesis)
Description	Number of participants who had complete control defined by no vomiting
Time Frame	During the 6 days following chemotherapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Granisetron, Dexamethasone, Aprepitant)
Arm/Group Description	Patients apply one patch of granisetron transdermal system to the upper outer arm on day 0 (at least 24 hours before intraperitoneal [IP] platinum therapy). Patients then receive dexamethasone PO on days 1-4, aprepitant IV over 15 minutes on day 1 (30 minutes before IP platinum therapy), and aprepitant PO on days 2-3. Adjuvant Therapy: Ancillary studies Aprepitant: Given IV and PO Carboplatin: Given IP Cisplatin: Given IP Dexamethasone: Given PO Granisetron Transdermal Patch: Apply one patch to upper arm Management of Therapy Complications: Ancillary studies Questionnaire Administration: Ancillary studies
Measure Participants	4
Count of Participants [Participants]	1 25%

2. Secondary Outcome

Title	Change in Vomiting, Nausea and Total FLIE Scores
Time Frame	Baseline to day 6

Outcome Measure Data

Analysis Population Description

Data was not collected. Funding withdrawn.

Arm/Group Title	Treatment (Granisetron, Dexamethasone, Aprepitant)
Arm/Group Description	Patients apply one patch of granisetron transdermal system to the upper outer arm on day 0 (at least 24 hours before intraperitoneal [IP] platinum therapy). Patients then receive dexamethasone PO on days 1-4, aprepitant IV over 15 minutes on day 1 (30 minutes before IP platinum therapy), and aprepitant PO on days 2-3. Adjuvant Therapy: Ancillary studies Aprepitant: Given IV and PO Carboplatin: Given IP Cisplatin: Given IP Dexamethasone: Given PO Granisetron Transdermal Patch: Apply one patch to upper arm Management of Therapy Complications: Ancillary studies Questionnaire Administration: Ancillary studies
Measure Participants	0

3. Secondary Outcome

Title	Frequency of Adverse Effects as Assessed by the NCI CTCAE v 4.0
Description	Adverse events at least possibly related to treatment
Time Frame	Up to day 6

Outcome Measure Data

Analysis Population Description

All eligible and evaluable subjects

Arm/Group Title	Treatment (Granisetron, Dexamethasone, Aprepitant)
Arm/Group Description	Patients apply one patch of granisetron transdermal system to the upper outer arm on day 0 (at least 24 hours before intraperitoneal [IP] platinum therapy). Patients then receive dexamethasone PO on days 1-4, aprepitant IV over 15 minutes on day 1 (30 minutes before IP platinum therapy), and aprepitant PO on days 2-3. Adjuvant Therapy: Ancillary studies Aprepitant: Given IV and PO Carboplatin: Given IP Cisplatin: Given IP Dexamethasone: Given PO Granisetron Transdermal Patch: Apply one patch to upper arm Management of Therapy Complications: Ancillary studies Questionnaire Administration: Ancillary studies
Measure Participants	4
Constipation	1 25%
Fatigue	1 25%
Diarrhea	1 25%
Hyponatremia	1 25%
Alanine Aminotransferase Increased	1 25%
GGT Increased	1 25%

4. Secondary Outcome

Title	Mean and Standard Deviation of Vomiting, Nausea, and Total FLIE Scores
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Data not collected. Funding withdrawn

Arm/Group Title	Treatment (Granisetron, Dexamethasone, Aprepitant)
Arm/Group Description	Patients apply one patch of granisetron transdermal system to the upper outer arm on day 0 (at least 24 hours before intraperitoneal [IP] platinum therapy). Patients then receive dexamethasone PO on days 1-4, aprepitant IV over 15 minutes on day 1 (30 minutes before IP platinum therapy), and aprepitant PO on days 2-3. Adjuvant Therapy: Ancillary studies Aprepitant: Given IV and PO Carboplatin: Given IP Cisplatin: Given IP Dexamethasone: Given PO Granisetron Transdermal Patch: Apply one patch to upper arm Management of Therapy Complications: Ancillary studies Questionnaire Administration: Ancillary studies
Measure Participants	0

5. Secondary Outcome

Title	Percentages of Patients With NIDL Based on FLIE
Time Frame	Up to day 6

Outcome Measure Data

Analysis Population Description

Data not collected. Funding withdrawn.

Arm/Group Title	Treatment (Granisetron, Dexamethasone, Aprepitant)
Arm/Group Description	Patients apply one patch of granisetron transdermal system to the upper outer arm on day 0 (at least 24 hours before intraperitoneal [IP] platinum therapy). Patients then receive dexamethasone PO on days 1-4, aprepitant IV over 15 minutes on day 1 (30 minutes before IP platinum therapy), and aprepitant PO on days 2-3. Adjuvant Therapy: Ancillary studies Aprepitant: Given IV and PO Carboplatin: Given IP Cisplatin: Given IP Dexamethasone: Given PO Granisetron Transdermal Patch: Apply one patch to upper arm Management of Therapy Complications: Ancillary studies Questionnaire Administration: Ancillary studies
Measure Participants	0

Adverse Events

Time Frame	Assessed day 6 while on treatment and up to 30 days after day 6.
Arm/Group Title	Treatment (Granisetron, Dexamethasone, Aprepitant)
Arm/Group Description	Patients apply one patch of granisetron transdermal system to the upper outer arm on day 0 (at least 24 hours before intraperitoneal [IP] platinum therapy). Patients then receive dexamethasone PO on days 1-4, aprepitant IV over 15 minutes on day 1 (30 minutes before IP platinum therapy), and aprepitant PO on days 2-3. Adjuvant Therapy: Ancillary studies Aprepitant: Given IV and PO Carboplatin: Given IP Cisplatin: Given IP Dexamethasone: Given PO Granisetron Transdermal Patch: Apply one patch to upper arm Management of Therapy Complications: Ancillary studies Questionnaire Administration: Ancillary studies
All Cause Mortality
	Treatment (Granisetron, Dexamethasone, Aprepitant)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Granisetron, Dexamethasone, Aprepitant)
	Affected / at Risk (%)	# Events
Total	0/4 (0%)
Other (Not Including Serious) Adverse Events
	Treatment (Granisetron, Dexamethasone, Aprepitant)
	Affected / at Risk (%)	# Events
Total	3/4 (75%)
Blood and lymphatic system disorders
Anemia	2/4 (50%)
Ear and labyrinth disorders
Tinnitus	1/4 (25%)
Gastrointestinal disorders
Constipation	3/4 (75%)
Diarrhea	2/4 (50%)
Mucositis Oral	1/4 (25%)
Nausea	2/4 (50%)
Esophagitis	1/4 (25%)
General disorders
Fatigue	2/4 (50%)
Investigations
Platelet Count Decreased	1/4 (25%)
Ggt Increased	1/4 (25%)
Neutrophil Count Decreased	2/4 (50%)
White Blood Cell Decreased	2/4 (50%)
Aspartate Aminotransferase Increased	1/4 (25%)
Alanine Aminotransferase Increased	1/4 (25%)
Metabolism and nutrition disorders
Hyponatremia	1/4 (25%)
Nervous system disorders
Headache	1/4 (25%)
Skin and subcutaneous tissue disorders
Alopecia	1/4 (25%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.