Aloxi for Prevention of Chemotherapy Induced Nausea and Vomiting in Malignant Glioma Patients Receiving Irinotecan With Bevacizumab

• Sponsor: Duke University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00636805
• Collaborator: Eisai Inc. (Industry), National Institute of Neurological Disorders and Stroke (NINDS) (NIH)
• Enrollment: 63
• Location: 1
• Arm: 1
• Duration (Months): 56
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

1. Primary Objective:

• To determine the efficacy and tolerability of palonosetron and dexamethasone in preventing acute CINV in brain tumor patients during the first 24 hours of receiving Irinotecan /Bevacizumab regimens.

1. Secondary Objective

• To determine the safety and tolerability of palonosetron in brain tumor patients.

• To determine the effects of glucocorticoid and anticonvulsants on the efficacy of palonosetron.

• To determine the efficacy of palonosetron and dexamethasone in preventing delayed CINV in brain tumor patients during days 2-5.

• To determine if patients receiving palonosetron have less fatigue than baseline.

Condition or Disease	Intervention/Treatment	Phase
Brain Cancer	Drug: Palonosetron (Aloxi) and Dexamethasone	Phase 2

Detailed Description

Before the patients receive the palonosetron, a physical exam and blood tests are performed to determine eligibility. If eligible and willing, subjects are given Palonosetron intravenously. Subjects are given the Palonosetron and Dexamethasone 30 minutes before the first dose of Irinotecan and Bevacizumab chemotherapy. The total expected duration of participation is 57 days. Subjects are also asked to complete 4 questionnaires about nausea and vomiting, as well as daily functioning and fatigue. Subjects are asked to complete these questionnaires before starting chemotherapy, the day of starting chemotherapy and for the next 4 days after receiving chemotherapy, for a total of 6 times. Subjects are asked to complete this set of questionnaires each of the 3 times that they receive chemotherapy during the 6-week treatment cycle.

The other treatments subjects would normally receive for their brain tumor and their routine care are not affected by the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 63 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: A Phase II Single Arm Trial of Palonosetron (PALO) for the Prevention of Acute and Delayed Chemotherapy Induced Nausea and Vomiting (CINV) in Malignant Glioma (MG) Patients Receiving Irinotecan in Combination With Bevacizumab
• Study Start Date: May 1, 2008
• Actual Primary Completion Date: Jan 1, 2013
• Actual Study Completion Date: Jan 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Patient receives IV Aloxi	Drug: Palonosetron (Aloxi) and Dexamethasone; single i.v. , dose of palonosetron 0.25 mg, and 10mg dexamethasone infused over 15 min, administered 30 min before the first dose Irinotecan and Bevacizumab chemotherapy.; Other Names: Aloxi

Outcome Measures

Primary Outcome Measures

1. Acute CINV (Chemotherapy Induced Nausea and Vomiting) CR (Complete Response) Rate [first 24 hours of the first week of chemotherapy]

   Acute Chemotherapy-Induced Nausea and Vomiting (CINV) complete response (CR) rate is defined as the percentage of patients who do not have an emetic episode or use antiemetic rescue medication during the first 24 hours following chemotherapy of the first cycle of treatment.

Secondary Outcome Measures

1. Acute Chemotherapy-Induced Nausea and Vomiting (CINV) Complete Response (CR) Rate by Corticosteroid Use at Baseline [Day 1 of the first week of chemotherapy]

   Acute Chemotherapy-Induced Nausea and Vomiting (CINV) complete response (CR) rate is defined as the percentage of patients who do not have an emetic episode or use antiemetic rescue medication during the first 24 hours following chemotherapy of the first cycle of treatment.

2. Acute Chemotherapy-Induced Nausea and Vomiting (CINV) Complete Response (CR) Rate by Anticoagulant Use at Baseline [Day 1 of the first week of chemotherapy]

   Acute Chemotherapy-Induced Nausea and Vomiting (CINV) complete response (CR) rate is defined as the percentage of patients who do not have an emetic episode or use antiemetic rescue medication during the first 24 hours following chemotherapy of the first cycle of treatment.

3. Delayed Chemotherapy-Induced Nausea and Vomiting (CINV) Complete Response (CR) Rate [Days 2-5 of the first week of chemotherapy]

   Delayed Chemotherapy-Induced Nausea and Vomiting (CINV) complete response (CR) rate is defined as the percentage of patients who do not have an emetic episode or use antiemetic rescue medication during days 2 through 5 of chemotherapy treatment during the first cycle of treatment

4. Percentage of Patients With ≥ Grade 3, Treatment-related Toxicities [6 weeks]

   Percentage of patients with ≥ grade 3, treatment-related toxicities using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.

5. Overall Mean Change in the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score From Baseline to Day 5 of the First Week of Chemotherapy [Baseline through day 5 of the first week of chemotherapy]

   Overall mean change in the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score from baseline to day 5 of the first week of chemotherapy. The FACIT-Fatigue is a 13-item validated questionnaire assessing the impact of fatigue on an individual's quality of life. The raw score range is 0-52 with higher scores indicating better quality of life. The mean change from baseline to day 5 was calculated by subtracting the baseline score from mean of the day 1-5 scores, thus a negative mean change represents worsening in quality of life due to fatigue.

6. Overall Mean Change in the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score From Baseline to Day 5 of the First Week of Chemotherapy by Acute Chemotherapy-Induced Nausea and Vomiting (CINV) Complete Response (CR) [Baseline through day 5 of the first week of chemotherapy]

   Overall mean change in the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score from baseline to day 5 of the first week of chemotherapy. The FACIT-Fatigue is a 13-item validated questionnaire assessing the impact of fatigue on an individual's quality of life. The raw score range is 0-52 with higher scores indicating better quality of life. The mean change from baseline to day 5 was calculated by subtracting the baseline score from the mean of the day 1-5 scores, thus a negative mean change represents worsening in quality of life due to fatigue. Acute CINV complete response (CR) is defined as not having an emetic episode or any use of antiemetic rescue medication during the first 24 hours following chemotherapy of the first cycle of treatment.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

In order to be included in the study, patients must meet all of the following criteria:

• Patients must have histologically confirmed diagnosis of primary malignant glioma (glioblastoma multiforme, gliosarcoma or anaplastic astrocytoma, or anaplastic oligodendroglioma) who are either chemotherapy naïve or non-naïve and scheduled to receive Irinotecan/Bevacizumab chemotherapy.

• Patients with recurrent disease whose diagnostic pathology confirmed malignant glioma (glioblastoma multiforme, gliosarcoma or anaplastic astrocytoma, or anaplastic oligodendroglioma) will not need re-biopsy.

• Age > or = 18 years.

• Patient is scheduled to receive Irinotecan/Bevacizumab chemotherapy every 2 weeks for one complete 6-week cycle.

• An interval of at least 6 weeks between prior surgical resection and study enrollment.

• An interval of at least 4 weeks between prior radiotherapy and enrollment on this protocol unless there is unequivocal evidence of tumor progression after radiotherapy or chemotherapy.

• The lab values following the prior chemotherapy must return within normal limits prior to study enrollment.

• Karnofsky > 60%.

• Hematocrit > 29%, absolute neutrophil count (ANC) > 1,500 cells/*l, platelets > 125,000 cells/*l.

• Serum creatinine < 1.5 mg/dl, serum glutamic-oxaloacetic transaminase (SGOT) and bilirubin < 1.5 times upper limit of normal.

• Patients on corticosteroids must be on a stable dose for 1 week prior to entry, and the dose should not be escalated over entry dose level, if clinically possible.

• Signed consent form approved by the Institutional Review Board prior to patient entry.

• No evidence of hemorrhage on the baseline MRI or CT scan.

• If sexually active, patients will take contraceptive measures for the duration of the treatments.

Exclusion Criteria:

Patients are excluded from this study if they meet any of the following criteria:

• Inability or unwillingness to understand or cooperate with study procedures.

• Received any intravenous drug with potential anti-emetic effect within 24 hours prior to the start of study-designated chemotherapeutic agent or be scheduled to receive any drug of this type (with the exception of administration of the palonosetron/dexamethasone infusion solution) at any time during the trial, including the following:

• 5 HT3 receptor antagonists;

• Dopamine receptor antagonists (metoclopramide);

• Phenothiazine anti-emetics (prochlorperazine, thiethylperazine and perphenazine);

• Diphenhydramine, scopolamine, chlorpheniramine maleate, trimethobenzamide. Diphenhydramine will be allowed if given for prophylactic treatment of hypersensitivity reactions associated with the administration of taxanes;

• Haloperidol, droperidol, tetrahydrocannabinol, or nabilone; and

• Any systemic corticosteroid (hydrocortisone, methylprednisolone, prednisone). Topical or inhaled preparations are allowed;

• Previous participation in any clinical trial involving palonosetron (RS-25259 of Syntex).

• Any vomiting, retching or NCI Common Toxicity Criteria version 3.0 grade 2-4 nausea (see Appendix 8.6) in the 24 hours preceding chemotherapy.

• Ongoing vomiting from any organic etiology.

• Will receive radiotherapy of upper abdomen or cranium within one week prior to or during the study.

• Received palonosetron within 14 days prior to study enrollment (AloxiTM).

• Evidence of central nervous system (CNS) hemorrhage on baseline MRI on CT scan.

• Co -medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids.

• Prophylactic medication for the prevention of nausea and vomiting 24 hours prior to the start of chemotherapy through 120 hours after the initiation of chemotherapy on Study Day 1 (Study Day 6) is prohibited, with the exception of the study drug. Corticosteroids will be allowed for treatment of cerebral swelling. Diphenhydramine will be allowed only if given for prophylactic treatment of hypersensitivity reactions associated with the administration of taxanes, as per the package insert for these agents. Rescue medication for treatment of nausea and vomiting is permitted after chemotherapy at the discretion of the investigator. The agent, dose, and time of administration will be recorded in the patient diary.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Duke University Medical Center	Durham	North Carolina	United States	27710

Sponsors and Collaborators

• Duke University
• Eisai Inc.
• National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

• Principal Investigator: Mary Lou Affronti, RN, MSN, ANP, Duke University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT00636805
• Other Study ID Numbers: Pro00002273; P50NS020023
• First Posted: Mar 14, 2008
• Last Update Posted: Apr 1, 2014
• Last Verified: Mar 1, 2014

• Keywords provided by Duke University: Aloxi; Brain Neoplasm, Primary; Brain Neoplasms, Malignant
• Additional relevant MeSH terms: Glioma; Brain Neoplasms; Vomiting; Dexamethasone; Palonosetron

Study Results

Participant Flow

Arm/Group Title	Patient Receives IV Aloxi
Arm/Group Description	Patient receives IV Aloxi Palonosetron (Aloxi) and Dexamethasone: single i.v. , dose of palonosetron 0.25 mg, and 10mg dexamethasone infused over 15 min, administered 30 min before the first dose Irinotecan and Bevacizumab chemotherapy.
Period Title: Overall Study
STARTED	63
COMPLETED	63
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Patient Receives IV Aloxi
Arm/Group Description	Patient receives IV Aloxi Palonosetron (Aloxi) and Dexamethasone: single i.v. , dose of palonosetron 0.25 mg, and 10mg dexamethasone infused over 15 min, administered 30 min before the first dose Irinotecan and Bevacizumab chemotherapy.
Overall Participants	63
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.2 (13.1)
Sex: Female, Male (Count of Participants)
Female	21 33.3%
Male	42 66.7%

Outcome Measures

1. Primary Outcome

Title	Acute CINV (Chemotherapy Induced Nausea and Vomiting) CR (Complete Response) Rate
Description	Acute Chemotherapy-Induced Nausea and Vomiting (CINV) complete response (CR) rate is defined as the percentage of patients who do not have an emetic episode or use antiemetic rescue medication during the first 24 hours following chemotherapy of the first cycle of treatment.
Time Frame	first 24 hours of the first week of chemotherapy

Outcome Measure Data

Analysis Population Description

Intent-to-treat; 11 patients did not complete the study measure for day 1 of the first week of chemotherapy

Arm/Group Title	Patient Receives IV Aloxi
Arm/Group Description	Patient receives IV Aloxi Palonosetron (Aloxi) and Dexamethasone: single i.v. , dose of palonosetron 0.25 mg, and 10mg dexamethasone infused over 15 min, administered 30 min before the first dose Irinotecan and Bevacizumab chemotherapy.
Measure Participants	52
Number (95% Confidence Interval) [percentage of participants]	62 98.4%

2. Secondary Outcome

Title	Acute Chemotherapy-Induced Nausea and Vomiting (CINV) Complete Response (CR) Rate by Corticosteroid Use at Baseline
Description	Acute Chemotherapy-Induced Nausea and Vomiting (CINV) complete response (CR) rate is defined as the percentage of patients who do not have an emetic episode or use antiemetic rescue medication during the first 24 hours following chemotherapy of the first cycle of treatment.
Time Frame	Day 1 of the first week of chemotherapy

Outcome Measure Data

Analysis Population Description

Intent-to-treat; 11 patients did not complete the study measure for day 1 of the first week of chemotherapy

Arm/Group Title	Patient Receives IV Aloxi
Arm/Group Description	Patient receives IV Aloxi Palonosetron (Aloxi) and Dexamethasone: single i.v. , dose of palonosetron 0.25 mg, and 10mg dexamethasone infused over 15 min, administered 30 min before the first dose Irinotecan and Bevacizumab chemotherapy.
Measure Participants	52
corticosteroid used at baseline	68 107.9%
no corticosteroid used at baseline	58 92.1%

3. Secondary Outcome

Title	Acute Chemotherapy-Induced Nausea and Vomiting (CINV) Complete Response (CR) Rate by Anticoagulant Use at Baseline
Description	Acute Chemotherapy-Induced Nausea and Vomiting (CINV) complete response (CR) rate is defined as the percentage of patients who do not have an emetic episode or use antiemetic rescue medication during the first 24 hours following chemotherapy of the first cycle of treatment.
Time Frame	Day 1 of the first week of chemotherapy

Outcome Measure Data

Analysis Population Description

Intent-to-treat; 11 patients did not complete the study measure for day 1 of the first week of chemotherapy

Arm/Group Title	Patient Receives IV Aloxi
Arm/Group Description	Patient receives IV Aloxi Palonosetron (Aloxi) and Dexamethasone: single i.v. , dose of palonosetron 0.25 mg, and 10mg dexamethasone infused over 15 min, administered 30 min before the first dose Irinotecan and Bevacizumab chemotherapy.
Measure Participants	52
anticoagulant used at baseline	61 96.8%
no anticoagulant used at baseline	63 100%

4. Secondary Outcome

Title	Delayed Chemotherapy-Induced Nausea and Vomiting (CINV) Complete Response (CR) Rate
Description	Delayed Chemotherapy-Induced Nausea and Vomiting (CINV) complete response (CR) rate is defined as the percentage of patients who do not have an emetic episode or use antiemetic rescue medication during days 2 through 5 of chemotherapy treatment during the first cycle of treatment
Time Frame	Days 2-5 of the first week of chemotherapy

Outcome Measure Data

Analysis Population Description

Intent-to-treat; 10 patients did not complete the study measure for days 2-5 of the first week of chemotherapy

Arm/Group Title	Patient Receives IV Aloxi
Arm/Group Description	Patient receives IV Aloxi Palonosetron (Aloxi) and Dexamethasone: single i.v. , dose of palonosetron 0.25 mg, and 10mg dexamethasone infused over 15 min, administered 30 min before the first dose Irinotecan and Bevacizumab chemotherapy.
Measure Participants	53
Number (95% Confidence Interval) [percentage of participants]	62 98.4%

5. Secondary Outcome

Title	Percentage of Patients With ≥ Grade 3, Treatment-related Toxicities
Description	Percentage of patients with ≥ grade 3, treatment-related toxicities using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patient Receives IV Aloxi
Arm/Group Description	Patient receives IV Aloxi Palonosetron (Aloxi) and Dexamethasone: single i.v. , dose of palonosetron 0.25 mg, and 10mg dexamethasone infused over 15 min, administered 30 min before the first dose Irinotecan and Bevacizumab chemotherapy.
Measure Participants	63
Number [participants]	0 0%

6. Secondary Outcome

Title	Overall Mean Change in the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score From Baseline to Day 5 of the First Week of Chemotherapy
Description	Overall mean change in the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score from baseline to day 5 of the first week of chemotherapy. The FACIT-Fatigue is a 13-item validated questionnaire assessing the impact of fatigue on an individual's quality of life. The raw score range is 0-52 with higher scores indicating better quality of life. The mean change from baseline to day 5 was calculated by subtracting the baseline score from mean of the day 1-5 scores, thus a negative mean change represents worsening in quality of life due to fatigue.
Time Frame	Baseline through day 5 of the first week of chemotherapy

Outcome Measure Data

Analysis Population Description

Intent-to-treat; 16 patients did not complete the study measure at baseline or on day 5 of the first week of chemotherapy

Arm/Group Title	Patient Receives IV Aloxi
Arm/Group Description	Patient receives IV Aloxi Palonosetron (Aloxi) and Dexamethasone: single i.v. , dose of palonosetron 0.25 mg, and 10mg dexamethasone infused over 15 min, administered 30 min before the first dose Irinotecan and Bevacizumab chemotherapy.
Measure Participants	47
Mean (95% Confidence Interval) [units on a scale]	-3.5

7. Secondary Outcome

Title	Overall Mean Change in the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score From Baseline to Day 5 of the First Week of Chemotherapy by Acute Chemotherapy-Induced Nausea and Vomiting (CINV) Complete Response (CR)
Description	Overall mean change in the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score from baseline to day 5 of the first week of chemotherapy. The FACIT-Fatigue is a 13-item validated questionnaire assessing the impact of fatigue on an individual's quality of life. The raw score range is 0-52 with higher scores indicating better quality of life. The mean change from baseline to day 5 was calculated by subtracting the baseline score from the mean of the day 1-5 scores, thus a negative mean change represents worsening in quality of life due to fatigue. Acute CINV complete response (CR) is defined as not having an emetic episode or any use of antiemetic rescue medication during the first 24 hours following chemotherapy of the first cycle of treatment.
Time Frame	Baseline through day 5 of the first week of chemotherapy

Outcome Measure Data

Analysis Population Description

Intent-to-treat; 16 patients did not complete the study measure at baseline or on day 5 of the first week of chemotherapy

Arm/Group Title	Patient Receives IV Aloxi
Arm/Group Description	Patient receives IV Aloxi Palonosetron (Aloxi) and Dexamethasone: single i.v. , dose of palonosetron 0.25 mg, and 10mg dexamethasone infused over 15 min, administered 30 min before the first dose Irinotecan and Bevacizumab chemotherapy.
Measure Participants	47
CR	-3.5
Not CR	-3.3

Adverse Events

Time Frame	6 weeks
Adverse Event Reporting Description	The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
Arm/Group Title	Patient Receives IV Aloxi
Arm/Group Description	Patient receives IV Aloxi Palonosetron (Aloxi) and Dexamethasone: single i.v. , dose of palonosetron 0.25 mg, and 10mg dexamethasone infused over 15 min, administered 30 min before the first dose Irinotecan and Bevacizumab chemotherapy.
All Cause Mortality
	Patient Receives IV Aloxi
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Patient Receives IV Aloxi
	Affected / at Risk (%)	# Events
Total	3/63 (4.8%)
Gastrointestinal disorders
Diarrhea	1/63 (1.6%)
Nausea	1/63 (1.6%)
General disorders
Fatigue	1/63 (1.6%)
Infections and infestations
Infection - Other (Specify, CSF)	1/63 (1.6%)
Infections and infestations	1/63 (1.6%)
Lung infection	1/63 (1.6%)
Investigations
White blood cell decreased	1/63 (1.6%)
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome	1/63 (1.6%)
Vascular disorders
Thromboembolic event	1/63 (1.6%)
Other (Not Including Serious) Adverse Events
	Patient Receives IV Aloxi
	Affected / at Risk (%)	# Events
Total	51/63 (81%)
Blood and lymphatic system disorders
Anemia	1/63 (1.6%)
Eye disorders
Blurred vision	12/63 (19%)
Gastrointestinal disorders
Constipation	16/63 (25.4%)
Diarrhea	20/63 (31.7%)
Gastritis	1/63 (1.6%)
Gastrointestinal disorders - Other, specify	1/63 (1.6%)
Hemorrhoids	2/63 (3.2%)
Mucositis	10/63 (15.9%)
Mucositis oral	1/63 (1.6%)
Nausea	24/63 (38.1%)
Esophageal ulcer	1/63 (1.6%)
Vomiting	10/63 (15.9%)
General disorders
Fatigue	20/63 (31.7%)
Infections and infestations
Infections and infestations - Other, specify	7/63 (11.1%)
Bladder infection	1/63 (1.6%)
pneumonia	1/63 (1.6%)
Injury, poisoning and procedural complications
Burn	1/63 (1.6%)
Investigations
White blood cell decreased	1/63 (1.6%)
Neutrophil count decreased	3/63 (4.8%)
Weight loss	7/63 (11.1%)
Metabolism and nutrition disorders
Anorexia	11/63 (17.5%)
Nervous system disorders
Ataxia	15/63 (23.8%)
Cognitive disturbance	19/63 (30.2%)
Confusion	18/63 (28.6%)
Dizziness	13/63 (20.6%)
Memory impairment	16/63 (25.4%)
Mood alteration	16/63 (25.4%)
Peripheral motor neuropathy	19/63 (30.2%)
Peripheral sensory neuropathy	6/63 (9.5%)
Seizure	10/63 (15.9%)
Depressed level of consciousness	23/63 (36.5%)
Dysphasia	9/63 (14.3%)
Tremor	11/63 (17.5%)
Headache	13/63 (20.6%)
Psychiatric disorders
Insomnia	18/63 (28.6%)
Renal and urinary disorders
Proteinuria	1/63 (1.6%)
Urinary incontinence	2/63 (3.2%)
Reproductive system and breast disorders
Reproductive system and breast disorders - Other, specify	10/63 (15.9%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	1/63 (1.6%)
Dyspnea	8/63 (12.7%)
Skin and subcutaneous tissue disorders
Rash maculo-papular	4/63 (6.3%)
Rash acneiform	3/63 (4.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Research site shall provide MGI copies of publication at least 30 days prior to submission to allow MGI to protect its copyrights, to determine any Confidential Information (CI) and to check for technical correctness. Site shall consider any MGI comments and delete any CI requested by MGI, unless CI removal changes accuracy or interpretation of results, in which case site and MGI will discuss timing of submission. MGI may request delay of up to 60 days to protect its copyright or patent rights.