A Study of LY2606368 (Prexasertib) in Patients With Solid Tumors With Replicative Stress or Homologous Repair Deficiency

• Sponsor: Dana-Farber Cancer Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT02873975
• Collaborator: (none)
• Enrollment: 27
• Location: 1
• Arms: 3
• Actual Duration (Months): 56.6
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This research study is studying a checkpoint kinase 1 (CHK1) inhibitor as a possible treatment for advanced solid tumors that harbor genetic alterations in the homologous repair (HR) pathway, genetic alterations that indicate replication stress, or with CCNE1 amplification.

Condition or Disease	Intervention/Treatment	Phase
Advanced Cancers	Drug: LY2606368	Phase 2

Detailed Description

This is an open label, phase II, two-arm study exploring the anti-tumor activity of the CHK1 inhibitor prexasertib (LY2606368) in patients with advanced solid tumors exhibiting one of the following:

1. Replicative stress, including MYC amplification, CCNE1 amplification, Rb loss, or an FBXW7 mutation

2. An HR deficiency, including tumors with genomic or somatic mutations of BRCA1, BRCA2, PALB2, RAD51C, RAD51D, ATR, ATM, CHK2, or the Fanconi anemia pathway genes

3. A CCNE1 amplification

Study Design

• Study Type: Interventional
• Actual Enrollment: 27 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of the CHK1 Inhibitor LY2606368 in Patients With Advanced Solid Tumors Exhibiting Replicative Stress or Homologous Recombination Repair Deficiency
• Actual Study Start Date: Oct 12, 2016
• Actual Primary Completion Date: Sep 30, 2020
• Actual Study Completion Date: Jul 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Homologous Repair (HR) Deficiency Cohort Prexasertib (LY2606368) will be administered as an IV infusion in patients with homologous repair (HR) deficiency on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour.	Drug: LY2606368; Other Names: Prexasertib
Experimental: Replicative Stress Cohort Prexasertib (LY2606368) will be administered as an IV infusion in patients with advanced solid tumors exhibiting replicative stress on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour.	Drug: LY2606368; Other Names: Prexasertib
Experimental: CCNE1 Amplification Cohort Prexasertib (LY2606368) will be administered as an IV infusion in patients with CCNE1 amplification on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour.	Drug: LY2606368; Other Names: Prexasertib

Outcome Measures

Primary Outcome Measures

1. Progression-Free Rate at 4 Month [at 4 month]

   Progression-Free Rate defines as the percentage of participants progression-free at 4 months in all arms, by RECIST 1.1 criteria. Progression-free rate will be estimated as binomial proportion and overall survival and progression-free survival estimates and curves will be generated using the Kaplan-Meier method.

Secondary Outcome Measures

1. Incidence of Grade 4 Treatment-Related Toxicity [Assessed cycle 1 at day 1, 8, 15 and 22, and cycle 2 at day 1 and 15, from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 55 day (range 6 - 539 days).]

   All grade 4 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEvE as reported on case report forms were counted. Incidence is the number of patients experiencing at least one treatment-related grade 4 AE of any type during the time of observation.

2. Objective Response Rate [Disease was evaluated radiologically at baseline and on treatment; Treatment continued until disease progression or unacceptable toxicity. Median treatment duration for this study cohort was 55 day (range 6 - 539 days).]

   The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

3. Median Overall Survival (OS) [Participants were followed long-term for survival months from the end of treatment until death or lost to follow-up. Median (range) follow-up was X months () in this study cohort.]

   OS based on the Kaplan-Meier method is defined as the time from study entry to death or censored at date last known alive.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Participants must have a pathologically confirmed advanced solid tumor for which standard therapy proven to provide clinical benefit does not exist or is no longer effective.

• Participants must have one of the following (confirmed via targeted NextGeneration sequencing [NGS] using the DFCI/BWH OncoPanel or another CLIA-certified method):

• For the replicative stress cohort: MYC amplification, CCNE1 amplification, Rb loss, FBXW7 mutation, or another genomic abnormality indicative of replicative stress as agreed upon with the principal investigator. OR

• For the HR deficiency cohort: genomic or somatic mutation in BRCA1, BRCA2, PALB2, RAD51C, RAD51D, ATR, ATM, CHK2, the Fanconi anemia pathway genes, or another genomic or somatic mutation in a known HR gene as agreed upon with the principal investigator.

• For the CCNE1 cohort: CCNE1 amplification of 6-fold or greater. Patients with borderline amplification levels may be considered following approval from the overall principal investigator.

• Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral CT scan, MRI, or calipers by clinical exam.

• Age ≥ 18 years.

• ECOG performance status < 2

• Participants must have adequate organ and marrow function as defined below:

• Absolute neutrophil count ≥ 1.5 K/uL

• Platelet count ≥ 100 K/uL

• Hemoglobin ≥ 9 g/dL (with or without transfusion support)

• Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN)

• AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional ULN, unless liver metastases are present and then ≤ 5 × institutional ULN is acceptable

• Serum creatinine ≤ 1.5 × institutional ULN

• Participants enrolling to the HR or replicative stress cohorts during Stage 1 must have disease that is amenable to biopsy and be willing to undergo a pre-treatment tumor biopsy.

• The potential effects of LY2606368 use during pregnancy and lactation are not known. Nonclinical studies of LY2606368 on pregnancy and fetal development have not been performed. To minimize any potential risks, men and women with reproductive potential should use medically approved contraceptive precautions during treatment and for 3 months following the last dose of LY2606368. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for 3 months after completion of LY2606368 administration.

• Ability to understand and the willingness to sign a written informed consent document.

• QTcF value of ≤ 470 msec on screening electrocardiogram (EKG)

Exclusion Criteria:

• Participants who have had chemotherapy, other investigational or biologic therapy, major surgery, or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin

1. prior to the planned first dose of LY2606368 therapy.

• Participants who have not recovered to eligibility levels from prior toxicity or adverse events as a result of previous treatment prior to the study.

• Participants who have received prior treatment with a CHK1 inhibitor.

• Participants who have received prior radiation therapy to > 25% of the bone marrow.

• Participants with known untreated brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Participants with a history of brain metastases that have been treated, are no longer taking corticosteroids, and have been stable on imaging for at least one month following the end of treatment are permitted.

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to LY2606368.

• Participants with a personal or family history of long QT syndrome.

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, NYHA Class III/IV heart failure, unstable angina pectoris, cardiac arrhythmia, myocardial infarction within 3 months of enrollment, or psychiatric illness/social situations that would limit compliance with study requirements.

• Pregnant or breastfeeding females. The potential effects of LY2606368 use during pregnancy and breastfeeding are not known and LY2606368 has the potential for teratogenic or abortifacient effects.

• Known HIV-positive participants are ineligible because these participants are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in HIV-positive participants when indicated.

• Participants enrolling to the HR or replicative stress cohort during Stage 1 may not be on anticoagulant therapy unless the treating investigator has deemed it safe to temporarily hold to facilitate the pre-treatment tumor biopsy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

• Dana-Farber Cancer Institute

Investigators

• Principal Investigator: Geoffrey Shapiro, MD, PhD, Dana-Farber Cancer Institute

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 26, 2018

More Information

Publications

None provided.

• Responsible Party: Geoffrey Shapiro, MD, PhD, Geoffrey Shapiro M.D., PhD, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT02873975
• Other Study ID Numbers: 16-281
• First Posted: Aug 22, 2016
• Last Update Posted: Aug 25, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Geoffrey Shapiro, MD, PhD, Geoffrey Shapiro M.D., PhD, Dana-Farber Cancer Institute: Advanced Cancers; Solid tumors; MYC amplification; CCNE1 amplification; Rb loss; FBXW7 mutation; BRCA1 mutation; BRCA2 mutation; PALB2 mutation; RAD51C mutation; RAD51D mutation; ATR mutation; ATM mutation; CHK2 mutation; Fanconi anemia

Study Results

Participant Flow

Arm/Group Title	Homologous Repair (HR) Deficiency Cohort	Replicative Stress Cohort	CCNE1 Amplification Cohort
Arm/Group Description	Prexasertib (LY2606368) will be administered as an IV infusion in patients with homologous repair (HR) deficiency on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour. LY2606368	Prexasertib (LY2606368) will be administered as an IV infusion in patients with advanced solid tumors exhibiting replicative stress on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour. LY2606368	Prexasertib (LY2606368) will be administered as an IV infusion in patients with CCNE1 amplification on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour. LY2606368
Period Title: Overall Study
STARTED	8	10	9
COMPLETED	8	10	9
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Homologous Repair (HR) Deficiency Cohort	Replicative Stress Cohort	CCNE1 Amplification Cohort	Total
Arm/Group Description	Prexasertib (LY2606368) will be administered as an IV infusion in patients with homologous repair (HR) deficiency on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour.	Prexasertib (LY2606368) will be administered as an IV infusion in patients with advanced solid tumors exhibiting replicative stress on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour.	Prexasertib (LY2606368) will be administered as an IV infusion in patients with CCNE1 amplification on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour.	Total of all reporting groups
Overall Participants	8	10	9	27
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.2 (9.5)	55.2 (14.2)	61.2 (11.6)	59.4 (12.1)
Sex: Female, Male (Count of Participants)
Female	5 62.5%	3 30%	5 55.6%	13 48.1%
Male	3 37.5%	7 70%	4 44.4%	14 51.9%
Race/Ethnicity, Customized (Count of Participants)
Non-Hispanic	8 100%	10 100%	9 100%	27 100%
Hispanic	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	8 100%	10 100%	9 100%	27 100%

Outcome Measures

1. Primary Outcome

Title	Progression-Free Rate at 4 Month
Description	Progression-Free Rate defines as the percentage of participants progression-free at 4 months in all arms, by RECIST 1.1 criteria. Progression-free rate will be estimated as binomial proportion and overall survival and progression-free survival estimates and curves will be generated using the Kaplan-Meier method.
Time Frame	at 4 month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Homologous Repair (HR) Deficiency Cohort	Replicative Stress Cohort	CCNE1 Amplification Cohort
Arm/Group Description	Prexasertib (LY2606368) will be administered as an IV infusion in patients with homologous repair (HR) deficiency on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour.	Prexasertib (LY2606368) will be administered as an IV infusion in patients with advanced solid tumors exhibiting replicative stress on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour.	Prexasertib (LY2606368) will be administered as an IV infusion in patients with CCNE1 amplification on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour.
Measure Participants	8	10	9
>= 4 months	25 312.5%	10 100%	44.4 493.3%
< 4 months	75 937.5%	90 900%	55.6 617.8%

2. Secondary Outcome

Title	Incidence of Grade 4 Treatment-Related Toxicity
Description	All grade 4 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEvE as reported on case report forms were counted. Incidence is the number of patients experiencing at least one treatment-related grade 4 AE of any type during the time of observation.
Time Frame	Assessed cycle 1 at day 1, 8, 15 and 22, and cycle 2 at day 1 and 15, from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 55 day (range 6 - 539 days).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Homologous Repair (HR) Deficiency Cohort	Replicative Stress Cohort	CCNE1 Amplification Cohort
Arm/Group Description	Prexasertib (LY2606368) will be administered as an IV infusion in patients with homologous repair (HR) deficiency on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour.	Prexasertib (LY2606368) will be administered as an IV infusion in patients with advanced solid tumors exhibiting replicative stress on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour.	Prexasertib (LY2606368) will be administered as an IV infusion in patients with CCNE1 amplification on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour.
Measure Participants	8	10	9
Count of Participants [Participants]	5 62.5%	7 70%	7 77.8%

3. Secondary Outcome

Title	Objective Response Rate
Description	The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
Time Frame	Disease was evaluated radiologically at baseline and on treatment; Treatment continued until disease progression or unacceptable toxicity. Median treatment duration for this study cohort was 55 day (range 6 - 539 days).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Homologous Repair (HR) Deficiency Cohort	Replicative Stress Cohort	CCNE1 Amplification Cohort
Arm/Group Description	Prexasertib (LY2606368) will be administered as an IV infusion in patients with homologous repair (HR) deficiency on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour.	Prexasertib (LY2606368) will be administered as an IV infusion in patients with advanced solid tumors exhibiting replicative stress on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour.	Prexasertib (LY2606368) will be administered as an IV infusion in patients with CCNE1 amplification on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour.
Measure Participants	8	10	9
Number [proportion of participant]	0	0	0.11

4. Secondary Outcome

Title	Median Overall Survival (OS)
Description	OS based on the Kaplan-Meier method is defined as the time from study entry to death or censored at date last known alive.
Time Frame	Participants were followed long-term for survival months from the end of treatment until death or lost to follow-up. Median (range) follow-up was X months () in this study cohort.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Assessed cycle 1 at day 1, 8, 15 and 22, and cycle 2 at day 1 and 15, from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 55 day (range 6 - 539 days).
Adverse Event Reporting Description	Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Arm/Group Title	Homologous Repair (HR) Deficiency Cohort		Replicative Stress Cohort		CCNE1 Amplification Cohort
Arm/Group Description	Prexasertib (LY2606368) will be administered as an IV infusion in patients with homologous repair (HR) deficiency on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour.		Prexasertib (LY2606368) will be administered as an IV infusion in patients with advanced solid tumors exhibiting replicative stress on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour.		Prexasertib (LY2606368) will be administered as an IV infusion in patients with CCNE1 amplification on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour.
All Cause Mortality
	Homologous Repair (HR) Deficiency Cohort		Replicative Stress Cohort		CCNE1 Amplification Cohort
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/8 (25%)		2/10 (20%)		0/9 (0%)
Serious Adverse Events
	Homologous Repair (HR) Deficiency Cohort		Replicative Stress Cohort		CCNE1 Amplification Cohort
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/8 (100%)		7/10 (70%)		9/9 (100%)
Blood and lymphatic system disorders
Anemia	3/8 (37.5%)		1/10 (10%)		3/9 (33.3%)
Blood and lymphatic system disorders - Other, specify	1/8 (12.5%)		0/10 (0%)		0/9 (0%)
Febrile neutropenia	0/8 (0%)		1/10 (10%)		1/9 (11.1%)
General disorders
Fatigue	1/8 (12.5%)		0/10 (0%)		0/9 (0%)
Infections and infestations
Lung infection	1/8 (12.5%)		0/10 (0%)		0/9 (0%)
Sepsis	0/8 (0%)		0/10 (0%)		1/9 (11.1%)
Investigations
Aspartate aminotransferase increased	0/8 (0%)		0/10 (0%)		1/9 (11.1%)
Blood bilirubin increased	0/8 (0%)		0/10 (0%)		2/9 (22.2%)
Neutrophil count decreased	8/8 (100%)		7/10 (70%)		9/9 (100%)
Platelet count decreased	4/8 (50%)		2/10 (20%)		4/9 (44.4%)
White blood cell decreased	6/8 (75%)		6/10 (60%)		8/9 (88.9%)
Metabolism and nutrition disorders
Hypoalbuminemia	0/8 (0%)		0/10 (0%)		1/9 (11.1%)
Hyponatremia	0/8 (0%)		0/10 (0%)		1/9 (11.1%)
Hypophosphatemia	0/8 (0%)		0/10 (0%)		1/9 (11.1%)
Other (Not Including Serious) Adverse Events
	Homologous Repair (HR) Deficiency Cohort		Replicative Stress Cohort		CCNE1 Amplification Cohort
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/8 (100%)		10/10 (100%)		9/9 (100%)
Blood and lymphatic system disorders
Anemia	7/8 (87.5%)		8/10 (80%)		8/9 (88.9%)
Lymph node pain	0/8 (0%)		0/10 (0%)		1/9 (11.1%)
Cardiac disorders
Atrial fibrillation	1/8 (12.5%)		0/10 (0%)		0/9 (0%)
Sinus bradycardia	2/8 (25%)		0/10 (0%)		0/9 (0%)
Sinus tachycardia	1/8 (12.5%)		4/10 (40%)		2/9 (22.2%)
Ear and labyrinth disorders
Ear and labyrinth disorders - Other, specify	0/8 (0%)		0/10 (0%)		1/9 (11.1%)
Eye disorders
Dry eye	1/8 (12.5%)		0/10 (0%)		0/9 (0%)
Eye disorders - Other, specify	2/8 (25%)		1/10 (10%)		0/9 (0%)
Eyelid function disorder	0/8 (0%)		0/10 (0%)		1/9 (11.1%)
Gastrointestinal disorders
Abdominal distension	1/8 (12.5%)		0/10 (0%)		0/9 (0%)
Abdominal pain	1/8 (12.5%)		2/10 (20%)		0/9 (0%)
Ascites	1/8 (12.5%)		0/10 (0%)		0/9 (0%)
Colonic obstruction	0/8 (0%)		1/10 (10%)		0/9 (0%)
Constipation	2/8 (25%)		1/10 (10%)		0/9 (0%)
Diarrhea	3/8 (37.5%)		5/10 (50%)		0/9 (0%)
Dyspepsia	1/8 (12.5%)		1/10 (10%)		0/9 (0%)
Flatulence	0/8 (0%)		2/10 (20%)		0/9 (0%)
Gastric hemorrhage	1/8 (12.5%)		0/10 (0%)		0/9 (0%)
Gastrointestinal disorders - Other, specify	2/8 (25%)		0/10 (0%)		0/9 (0%)
Hemorrhoids	1/8 (12.5%)		0/10 (0%)		0/9 (0%)
Mucositis oral	2/8 (25%)		0/10 (0%)		0/9 (0%)
Nausea	5/8 (62.5%)		3/10 (30%)		0/9 (0%)
Stomach pain	1/8 (12.5%)		0/10 (0%)		0/9 (0%)
Toothache	1/8 (12.5%)		0/10 (0%)		0/9 (0%)
Vomiting	2/8 (25%)		0/10 (0%)		0/9 (0%)
General disorders
Edema limbs	3/8 (37.5%)		0/10 (0%)		0/9 (0%)
Fatigue	6/8 (75%)		0/10 (0%)		0/9 (0%)
Fever	5/8 (62.5%)		0/10 (0%)		0/9 (0%)
Hepatobiliary disorders
Portal hypertension	1/8 (12.5%)		0/10 (0%)		0/9 (0%)
Infections and infestations
Infections and infestations - Other, specify	1/8 (12.5%)		0/10 (0%)		0/9 (0%)
Injury, poisoning and procedural complications
Bruising	1/8 (12.5%)		0/10 (0%)		0/9 (0%)
Dermatitis radiation	1/8 (12.5%)		0/10 (0%)		0/9 (0%)
Investigations
Alkaline phosphatase increased	3/8 (37.5%)		0/10 (0%)		0/9 (0%)
Aspartate aminotransferase increased	2/8 (25%)		0/10 (0%)		0/9 (0%)
Blood bilirubin increased	2/8 (25%)		0/10 (0%)		0/9 (0%)
Creatinine increased	1/8 (12.5%)		0/10 (0%)		0/9 (0%)
Neutrophil count decreased	3/8 (37.5%)		0/10 (0%)		0/9 (0%)
Platelet count decreased	6/8 (75%)		0/10 (0%)		0/9 (0%)
White blood cell decreased	5/8 (62.5%)		0/10 (0%)		0/9 (0%)
Metabolism and nutrition disorders
Anorexia	1/8 (12.5%)		0/10 (0%)		0/9 (0%)
Hypercalcemia	1/8 (12.5%)		0/10 (0%)		0/9 (0%)
Hyperglycemia	2/8 (25%)		0/10 (0%)		0/9 (0%)
Hyperkalemia	1/8 (12.5%)		0/10 (0%)		0/9 (0%)
Hypoalbuminemia	3/8 (37.5%)		0/10 (0%)		0/9 (0%)
Hypocalcemia	1/8 (12.5%)		0/10 (0%)		0/9 (0%)
Hypokalemia	1/8 (12.5%)		0/10 (0%)		0/9 (0%)
Hypomagnesemia	2/8 (25%)		0/10 (0%)		0/9 (0%)
Hyponatremia	5/8 (62.5%)		0/10 (0%)		0/9 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/8 (12.5%)		0/10 (0%)		0/9 (0%)
Back pain	2/8 (25%)		0/10 (0%)		0/9 (0%)
Chest wall pain	1/8 (12.5%)		0/10 (0%)		0/9 (0%)
Musculoskeletal and connective tissue disorder - Other, specify	1/8 (12.5%)		0/10 (0%)		0/9 (0%)
Myalgia	2/8 (25%)		0/10 (0%)		0/9 (0%)
Pain in extremity	1/8 (12.5%)		0/10 (0%)		0/9 (0%)
Nervous system disorders
Headache	1/8 (12.5%)		0/10 (0%)		0/9 (0%)
Psychiatric disorders
Insomnia	1/8 (12.5%)		0/10 (0%)		0/9 (0%)
Renal and urinary disorders
Hematuria	1/8 (12.5%)		0/10 (0%)		0/9 (0%)
Reproductive system and breast disorders
Pelvic pain	1/8 (12.5%)		0/10 (0%)		0/9 (0%)
Prostatic obstruction	1/8 (12.5%)		0/10 (0%)		0/9 (0%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	1/8 (12.5%)		0/10 (0%)		0/9 (0%)
Cough	2/8 (25%)		0/10 (0%)		0/9 (0%)
Dyspnea	2/8 (25%)		0/10 (0%)		0/9 (0%)
Epistaxis	2/8 (25%)		0/10 (0%)		0/9 (0%)
Respiratory, thoracic and mediastinal disorders - Other, specify	1/8 (12.5%)		0/10 (0%)		0/9 (0%)
Skin and subcutaneous tissue disorders
Pruritus	1/8 (12.5%)		0/10 (0%)		0/9 (0%)
Skin and subcutaneous tissue disorders - Other, specify	2/8 (25%)		0/10 (0%)		0/9 (0%)
Vascular disorders
Hypertension	1/8 (12.5%)		0/10 (0%)		0/9 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.