Study of CBP501 + Pemetrexed + Cisplatin on MPM (Phase I/II)

• Sponsor: CanBas Co. Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00700336
• Collaborator: (none)
• Enrollment: 69
• Locations: 12
• Arms: 3
• Duration (Months): 54
• Patients Per Site: 5.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The phase I part of the study is a dose-finding study of escalating doses of CBP501 combined with full-dose cisplatin and pemetrexed in patients with histologically confirmed solid malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective or would otherwise be eligible for cisplatin and pemetrexed as first-line therapy. The maximum tolerated dose (MTD) will be determined based on DLTs occurring during the first treatment cycle. Pharmacokinetics of the triplet combination will be assessed during the phase I part of the trial.

The phase II part will evaluate full-dose cisplatin and pemetrexed combined with CBP501 (at the MTD determined in the phase I part) in previously untreated, unresectable malignant pleural mesothelioma patients. Patients will be randomized in a 2 : 1 ratio to pemetrexed, cisplatin and CBP501 (Arm A) or to pemetrexed and cisplatin (Arm B); randomization will be stratified according to histology and performance status.

Condition or Disease	Intervention/Treatment	Phase
Malignant Pleural Mesothelioma; Solid Tumors	Drug: pemetrexed, cisplatin and CBP501; Drug: pemetrexed and cisplatin; Drug: pemetrexed, cisplatin and CBP501, dose finding	Phase 1/Phase 2

Detailed Description

This is an open-label, multicenter, international, phase I-II study. The phase I part, a dose-finding study of escalating doses of CBP501 combined with fixed full-dose cisplatin and pemetrexed, has been completed and results are presented in this report. MTD was determined on DLT occurring during the first cycle. This phase I part was evaluated in a patient population with advanced solid tumors The phase II part will evaluate full-dose cisplatin and pemetrexed combined with CBP501 at the MTD determined in the phase I part. Patients will be randomized in a 2:1 ratio to pemetrexed, cisplatin and CBP501 (Arm A) or pemetrexed and cisplatin (Arm B). This phase II part will be evaluated in chemotherapy-naïve patients with malignant pleural mesothelioma

Randomization will be stratified by:

• Histology: epithelial vs other (sarcomatoid or biphasic)

• Performance status: 0-1 vs 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 69 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I/II Study of a Triplet Combination of CBP501, Pemetrexed and Cisplatin in Patients With Advanced Solid Tumors and in Chemotherapy-naïve Patients With Malignant Pleural Mesothelioma
• Study Start Date: May 1, 2008
• Actual Primary Completion Date: Jul 1, 2012
• Actual Study Completion Date: Nov 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pemetrexed, Cisplatin, and CBP501: Phase 2 pemetrexed, cisplatin and CBP501	Drug: pemetrexed, cisplatin and CBP501; CBP501 25 mg/m2, Pemetrexed 500 mg/m2, cisplatin 75 mg/m2 CBP501 for injection is provided in single dose vials (20 mg) containing a sterile lyophilized powder comprising CBP501 peptide acetate salt (peptide base units). For administration, vial contents are reconstituted in 5% Dextrose Injection, USP, and added to a 100 mL IV bag of 5% Dextrose Injection, USP. Pemetrexed: A commercial formulation of pemetrexed will be used, with reconstitution in 20mL 0.9% sodium chloride solution for injection, then dilution to 100mL. Cisplatin: A commercial formulation will be used and will be diluted in 250 mL of normal saline for administration.; Other Names: Arm A
Active Comparator: Pemetrexed and Cisplatin: Phase 2 pemetrexed and cisplatin	Drug: pemetrexed and cisplatin; Pemetrexed 500 mg/m2, cisplatin 75 mg/m2 Pemetrexed: A commercial formulation of pemetrexed will be used, with reconstitution in 20mL 0.9% sodium chloride solution for injection, then dilution to 100mL. Cisplatin: A commercial formulation will be used and will be diluted in 250 mL of normal saline for administration.; Other Names: Arm B
Experimental: Pemetrexed, Cisplatin, and CBP501:Phase 1 MTD, which was equal to recommended dose for the Phase II part, was determined by 6 patients (3+3)	Drug: pemetrexed, cisplatin and CBP501, dose finding; Dose level 1: CBP501 16 mg/m2, Pemetrexed 500 mg/m2, cisplatin 75 mg/m2 Dose level 2: CBP501 25 mg/m2, Pemetrexed 500 mg/m2, cisplatin 75 mg/m2 CBP501 for injection is provided in single dose vials (20 mg) containing a sterile lyophilized powder comprising CBP501 peptide acetate salt (peptide base units). For administration, vial contents are reconstituted in 5% Dextrose Injection, USP, and added to a 100 mL IV bag of 5% Dextrose Injection, USP. Pemetrexed: A commercial formulation of pemetrexed will be used, with reconstitution in 20mL 0.9% sodium chloride solution for injection, then dilution to 100mL. Cisplatin: A commercial formulation will be used and will be diluted in 250 mL of normal saline for administration.; Other Names: Phase I part Dose finding

Outcome Measures

Primary Outcome Measures

1. 4M PFS Rate of Patients With Previously Untreated, Unresectable Malignant Pleural Mesothelioma (MPM) Treated With CBP501, Pemetrexed and Cisplatin [End of study]

   Planned: Forty-two patients were to be treated in Arm A. If ≥ 23 patients (>54%) were free of progression and death at 4 months, then the study regimen would be considered for further evaluation in this indication.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Signed informed consent obtained prior to initiation of any study-specific procedures

2. Phase I: Histologically confirmed solid malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective or would otherwise be eligible for cisplatin and pemetrexed as first-line therapy

Phase II: Histologically or cytologically confirmed diagnosis of malignant pleural mesothelioma (MPM), not amenable for radical resection, who has not received previous chemotherapy or other systemic treatment

1. Measurable disease according to the modified Response Evaluation Criteria in Solid Tumors (RECIST, see below)

2. Male or female patients aged at least 18 years

3. ECOG Performance Status (PS): 0-2

4. Previous anticancer treatment must be discontinued at least 3 weeks prior to first dose of study treatment (6 weeks for mitomycin C; 6 weeks for anti-androgen therapy if discontinued prior to treatment initiation, with the exception of 8 weeks for bicalutamide)

5. Life expectancy greater than 3 months

6. Adequate organ function

7. Female patients of child-bearing potential must have a negative pregnancy test and be using at least one form of contraception as approved by the Investigator for 4 weeks prior to the study and 4 months after the last dose of study drug. For the purposes of this study, child-bearing potential is defined as: "All female patients unless they are post-menopausal for at least one year or are surgically sterile"

8. Male patients must use a form of barrier contraception approved by the investigator during the study and for 4 months after the last dose of study drug

9. Ability to cooperate with the treatment and follow-up

Exclusion Criteria:

1. Radiation therapy to more than 30% of the bone marrow prior to entry into the study

2. Phase II only: Mesothelioma originating outside the pleura (e.g.: peritoneum)

3. Absence of measurable lesions

4. The patient has an ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, uncontrolled thrombotic or hemorrhagic disorder, or any other serious uncontrolled medical disorders in the opinion of the investigator.

5. Any previous history of another malignancy within 5 years of study entry (other than cured basal cell carcinoma of the skin or cured in-situ carcinoma of the cervix)

6. Presence of any significant central nervous system or psychiatric disorder(s) that would hamper the patient's compliance

7. Evidence of peripheral neuropathy > grade 1 according to NCI-CTCAE Version 3

8. Treatment with any other investigational agent, or participation in another clinical trial within 28 days prior to study entry

9. Pregnant or breast-feeding patients or any patient with childbearing potential not using adequate contraception

10. Known HIV, HBV, HCV infection

11. Presence of CNS metastases

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Scottsdale	Arizona	United States	85259
2	Arizona Cancer Center	Tucson	Arizona	United States	85719-1454
3	City of Hope	Duarte	California	United States	91010
4	University of Chicago	Chicago	Illinois	United States	60637
5	Karmanos Cancer Institute/Wayne State University	Detroit	Michigan	United States	48201
6	Nevada Cancer Institute	Las Vegas	Nevada	United States	89135
7	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87131
8	Memorial-Sloan Kettering Cancer Center	New York	New York	United States	10022
9	Cleveland Clinic	Cleveland	Ohio	United States	44195
10	Penn State Milton S. Hershey Medical Ctr.	Hershey	Pennsylvania	United States	17033
11	Cancer Therapy & Research Center	San Antonio	Texas	United States	78229
12	Huntsman Cancer Institute	Salt Lake City	Utah	United States	84112

Sponsors and Collaborators

• CanBas Co. Ltd.

Investigators

• Principal Investigator: Lee Krug, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

• Matsumoto Y, Shindo Y, Takakusagi Y, Takakusagi K, Tsukuda S, Kusayanagi T, Sato H, Kawabe T, Sugawara F, Sakaguchi K. Screening of a library of T7 phage-displayed peptides identifies alphaC helix in 14-3-3 protein as a CBP501-binding site. Bioorg Med Chem. 2011 Dec 1;19(23):7049-56. doi: 10.1016/j.bmc.2011.10.004. Epub 2011 Oct 7.
• Mine N, Yamamoto S, Saito N, Yamazaki S, Suda C, Ishigaki M, Kufe DW, Von Hoff DD, Kawabe T. CBP501-calmodulin binding contributes to sensitizing tumor cells to cisplatin and bleomycin. Mol Cancer Ther. 2011 Oct;10(10):1929-38. doi: 10.1158/1535-7163.MCT-10-1139. Epub 2011 Aug 10.
• Sha SK, Sato T, Kobayashi H, Ishigaki M, Yamamoto S, Sato H, Takada A, Nakajyo S, Mochizuki Y, Friedman JM, Cheng FC, Okura T, Kimura R, Kufe DW, Vonhoff DD, Kawabe T. Cell cycle phenotype-based optimization of G2-abrogating peptides yields CBP501 with a unique mechanism of action at the G2 checkpoint. Mol Cancer Ther. 2007 Jan;6(1):147-53.
• Shapiro GI, Tibes R, Gordon MS, Wong BY, Eder JP, Borad MJ, Mendelson DS, Vogelzang NJ, Bastos BR, Weiss GJ, Fernandez C, Sutherland W, Sato H, Pierceall WE, Weaver D, Slough S, Wasserman E, Kufe DW, Von Hoff D, Kawabe T, Sharma S. Phase I studies of CBP501, a G2 checkpoint abrogator, as monotherapy and in combination with cisplatin in patients with advanced solid tumors. Clin Cancer Res. 2011 May 15;17(10):3431-42. doi: 10.1158/1078-0432.CCR-10-2345. Epub 2011 Jan 10.
• Suganuma M, Kawabe T, Hori H, Funabiki T, Okamoto T. Sensitization of cancer cells to DNA damage-induced cell death by specific cell cycle G2 checkpoint abrogation. Cancer Res. 1999 Dec 1;59(23):5887-91.

• Responsible Party: CanBas Co. Ltd.
• ClinicalTrials.gov Identifier: NCT00700336
• Other Study ID Numbers: CBP08-01
• First Posted: Jun 18, 2008
• Last Update Posted: Jul 20, 2021
• Last Verified: Jun 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by CanBas Co. Ltd.: malignant pleural mesothelioma; solid tumors
• Additional relevant MeSH terms: Mesothelioma; Mesothelioma, Malignant; Cisplatin; Pemetrexed

Study Results

Participant Flow

Arm/Group Title	Pemetrexed, Cisplatin and CBP501: Phase 2	Pemetrexed and Cisplatin: Phase 2	Pemetrexed, Cisplatin and CBP501: Phase 1
Arm/Group Description	pemetrexed, cisplatin and CBP501: CBP501 for injection is provided in single dose vials (20 mg) containing a sterile lyophilized powder comprising CBP501 peptide acetate salt (peptide base units). For administration, vial contents are reconstituted in 5% Dextrose Injection, USP, and added to a 100 mL IV bag of 5% Dextrose Injection, USP. Pemetrexed: A commercial formulation of pemetrexed will be used, with reconstitution in 20mL 0.9% sodium chloride solution for injection, then dilution to 100mL. Cisplatin: A commercial formulation will be used and will be diluted in 250 mL of normal saline for administration.	pemetrexed and cisplatin: Pemetrexed: A commercial formulation of pemetrexed will be used, with reconstitution in 20mL 0.9% sodium chloride solution for injection, then dilution to 100mL. Cisplatin: A commercial formulation will be used and will be diluted in 250 mL of normal saline for administration.	DL1: CBP501 16mg/m2, pemetrexed 500mg/m2, cisplatin 75mg/m2 DL2: CBP501 25mg/m2, pemetrexed 500mg/m2, cisplatin 75mg/m2
Period Title: Overall Study
STARTED	40	23	6
COMPLETED	40	23	6
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Pemetrexed, Cisplatin, and CBP501: Phase 2	Pemetrexed and Cisplatin: Phase 2	Pemetrexed, Cisplatin, and CBP501: Phase 1	Total
Arm/Group Description	pemetrexed, cisplatin and CBP501 pemetrexed, cisplatin and CBP501: CBP501 for injection is provided in single dose vials (20 mg) containing a sterile lyophilized powder comprising CBP501 peptide acetate salt (peptide base units). For administration, vial contents are reconstituted in 5% Dextrose Injection, USP, and added to a 100 mL IV bag of 5% Dextrose Injection, USP. Pemetrexed: A commercial formulation of pemetrexed will be used, with reconstitution in 20mL 0.9% sodium chloride solution for injection, then dilution to 100mL. Cisplatin: A commercial formulation will be used and will be diluted in 250 mL of normal saline for administration.	pemetrexed and cisplatin pemetrexed and cisplatin: Pemetrexed: A commercial formulation of pemetrexed will be used, with reconstitution in 20mL 0.9% sodium chloride solution for injection, then dilution to 100mL. Cisplatin: A commercial formulation will be used and will be diluted in 250 mL of normal saline for administration.	DL1: CBP501 16mg/m2, Alimta 500mg/m2, cisplatin 75mg/m2 DL2: CBP501 25mg/m2, Alimta 500mg/m2, cisplatin 75mg/m2	Total of all reporting groups
Overall Participants	40	23	6	69
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63 (10.03)	66.3 (12.10)	62.8 (13.61)	64.2 (10.86)
Sex: Female, Male (Count of Participants)
Female	8 20%	3 13%	1 16.7%	12 17.4%
Male	32 80%	20 87%	5 83.3%	57 82.6%

Outcome Measures

1. Primary Outcome

Title	4M PFS Rate of Patients With Previously Untreated, Unresectable Malignant Pleural Mesothelioma (MPM) Treated With CBP501, Pemetrexed and Cisplatin
Description	Planned: Forty-two patients were to be treated in Arm A. If ≥ 23 patients (>54%) were free of progression and death at 4 months, then the study regimen would be considered for further evaluation in this indication.
Time Frame	End of study

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pemetrexed, Cisplatin, and CBP501	Pemetrexed and Cisplatin
Arm/Group Description	Pemetrexed, Cisplatin, and CBP501 administered once every 3 weeks	Pemetrexed and Cisplatin every three weeks
Measure Participants	40	23
4M PFS by Independent Image Review	25 62.5%	9 39.1%
4M PFS by Site assess	27 67.5%	13 56.5%

Adverse Events

Arm/Group Title	Pemetrexed, Cisplatin, and CBP501: Phase 2		Pemetrexed and Cisplatin: Phase 2		Pemetrexed, Cisplatin, and CBP501: Phase 1
Arm/Group Description	pemetrexed, cisplatin and CBP501 pemetrexed, cisplatin and CBP501: CBP501 for injection is provided in single dose vials (20 mg) containing a sterile lyophilized powder comprising CBP501 peptide acetate salt (peptide base units). For administration, vial contents are reconstituted in 5% Dextrose Injection, USP, and added to a 100 mL IV bag of 5% Dextrose Injection, USP. Pemetrexed: A commercial formulation of pemetrexed will be used, with reconstitution in 20mL 0.9% sodium chloride solution for injection, then dilution to 100mL. Cisplatin: A commercial formulation will be used and will be diluted in 250 mL of normal saline for administration.		pemetrexed and cisplatin pemetrexed and cisplatin: Pemetrexed: A commercial formulation of pemetrexed will be used, with reconstitution in 20mL 0.9% sodium chloride solution for injection, then dilution to 100mL. Cisplatin: A commercial formulation will be used and will be diluted in 250 mL of normal saline for administration.		DL1: CBP501 16mg/m2, Alimta 500mg/m2, cisplatin 75mg/m2 DL2: CBP501 25mg/m2, Alimta 500mg/m2, cisplatin 75mg/m2
All Cause Mortality
	Pemetrexed, Cisplatin, and CBP501: Phase 2		Pemetrexed and Cisplatin: Phase 2		Pemetrexed, Cisplatin, and CBP501: Phase 1
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/40 (2.5%)		1/23 (4.3%)		4/6 (66.7%)
Serious Adverse Events
	Pemetrexed, Cisplatin, and CBP501: Phase 2		Pemetrexed and Cisplatin: Phase 2		Pemetrexed, Cisplatin, and CBP501: Phase 1
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/40 (52.5%)		13/23 (56.5%)		5/6 (83.3%)
Blood and lymphatic system disorders
Lymphopenia	2/40 (5%)		1/23 (4.3%)		0/6 (0%)
Gastrointestinal disorders
abdominal pain	0/40 (0%)		3/23 (13%)		1/6 (16.7%)
Nausea	3/40 (7.5%)		2/23 (8.7%)		0/6 (0%)
Vomiting	4/40 (10%)		1/23 (4.3%)		0/6 (0%)
General disorders
Fatigue	7/40 (17.5%)		3/23 (13%)		0/6 (0%)
Chest pain	0/40 (0%)		0/23 (0%)		1/6 (16.7%)
Infections and infestations
Pneumonia	0/40 (0%)		0/23 (0%)		1/6 (16.7%)
Investigations
Haemoglobin decreased	3/40 (7.5%)		0/23 (0%)		0/6 (0%)
Metabolism and nutrition disorders
Dehydration	4/40 (10%)		4/23 (17.4%)		0/6 (0%)
Hyperglycemia	3/40 (7.5%)		1/23 (4.3%)		0/6 (0%)
Hyponatremia	2/40 (5%)		2/23 (8.7%)		0/6 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progressed	2/40 (5%)		1/23 (4.3%)		0/6 (0%)
Renal and urinary disorders
renal failure	2/40 (5%)		0/23 (0%)		0/6 (0%)
Respiratory, thoracic and mediastinal disorders
dyspnea	3/40 (7.5%)		0/23 (0%)		0/6 (0%)
Hypoxia	2/40 (5%)		0/23 (0%)		0/6 (0%)
pulmonary embolism	2/40 (5%)		2/23 (8.7%)		2/6 (33.3%)
Vascular disorders
deep vein thrombosis	2/40 (5%)		1/23 (4.3%)		1/6 (16.7%)
Syncope	0/40 (0%)		0/23 (0%)		2/6 (33.3%)
Other (Not Including Serious) Adverse Events
	Pemetrexed, Cisplatin, and CBP501: Phase 2		Pemetrexed and Cisplatin: Phase 2		Pemetrexed, Cisplatin, and CBP501: Phase 1
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	28/40 (70%)		15/23 (65.2%)		6/6 (100%)
Blood and lymphatic system disorders
anemia	7/40 (17.5%)		8/23 (34.8%)		3/6 (50%)
leukopenia	2/40 (5%)		1/23 (4.3%)		0/6 (0%)
lymphopenia	5/40 (12.5%)		1/23 (4.3%)		0/6 (0%)
neutropenia	2/40 (5%)		2/23 (8.7%)		1/6 (16.7%)
Ear and labyrinth disorders
tinnitus	5/40 (12.5%)		2/23 (8.7%)		0/6 (0%)
Eye disorders
lacrimation increased	2/40 (5%)		2/23 (8.7%)		1/6 (16.7%)
vision blurred	2/40 (5%)		0/23 (0%)		1/6 (16.7%)
Gastrointestinal disorders
abdominal discomfort	2/40 (5%)		1/23 (4.3%)		0/6 (0%)
abdominal distension	1/40 (2.5%)		3/23 (13%)		2/6 (33.3%)
abdominal pain	4/40 (10%)		1/23 (4.3%)		1/6 (16.7%)
constipation	21/40 (52.5%)		15/23 (65.2%)		4/6 (66.7%)
diarrhea	8/40 (20%)		4/23 (17.4%)		2/6 (33.3%)
dry mouth	2/40 (5%)		2/23 (8.7%)		0/6 (0%)
dyspepsia	5/40 (12.5%)		2/23 (8.7%)		1/6 (16.7%)
nausea	24/40 (60%)		13/23 (56.5%)		5/6 (83.3%)
stomatitis	2/40 (5%)		1/23 (4.3%)		3/6 (50%)
vomiting	8/40 (20%)		9/23 (39.1%)		1/6 (16.7%)
General disorders
asthenia	2/40 (5%)		0/23 (0%)		0/6 (0%)
chest discomfort	2/40 (5%)		1/23 (4.3%)		0/6 (0%)
chest pain	7/40 (17.5%)		4/23 (17.4%)		0/6 (0%)
chills	2/40 (5%)		0/23 (0%)		2/6 (33.3%)
fatigue	24/40 (60%)		15/23 (65.2%)		5/6 (83.3%)
infusion related reactions	28/40 (70%)		0/23 (0%)		2/6 (33.3%)
infusion site rash	2/40 (5%)		0/23 (0%)		0/6 (0%)
mucosal inflammation	2/40 (5%)		1/23 (4.3%)		0/6 (0%)
oedema peripheral	5/40 (12.5%)		6/23 (26.1%)		0/6 (0%)
pain	1/40 (2.5%)		2/23 (8.7%)		0/6 (0%)
pyrexia	6/40 (15%)		3/23 (13%)		1/6 (16.7%)
Immune system disorders
hypersensitivity	0/40 (0%)		2/23 (8.7%)		0/6 (0%)
Infections and infestations
oral candidiasis	2/40 (5%)		0/23 (0%)		0/6 (0%)
Investigations
blood albumin decreased	2/40 (5%)		0/23 (0%)		0/6 (0%)
blood creatinine increased	7/40 (17.5%)		3/23 (13%)		1/6 (16.7%)
blood glucose increased	2/40 (5%)		0/23 (0%)		0/6 (0%)
blood sodium decreased	2/40 (5%)		0/23 (0%)		0/6 (0%)
ECG QT prolonged	2/40 (5%)		1/23 (4.3%)		1/6 (16.7%)
hemoglobin decreased	7/40 (17.5%)		0/23 (0%)		0/6 (0%)
neutrophil count decreased	2/40 (5%)		0/23 (0%)		0/6 (0%)
platelet count decreased	3/40 (7.5%)		1/23 (4.3%)		0/6 (0%)
prothrombin time prolonged	2/40 (5%)		0/23 (0%)		0/6 (0%)
weight decreased	5/40 (12.5%)		1/23 (4.3%)		0/6 (0%)
WBC decreased	4/40 (10%)		0/23 (0%)		0/6 (0%)
Metabolism and nutrition disorders
decreased apetite	18/40 (45%)		12/23 (52.2%)		0/6 (0%)
dehydration	6/40 (15%)		2/23 (8.7%)		0/6 (0%)
hyperglycemia	4/40 (10%)		2/23 (8.7%)		0/6 (0%)
hypoalbuminemia	2/40 (5%)		1/23 (4.3%)		0/6 (0%)
hypokalemia	2/40 (5%)		1/23 (4.3%)		0/6 (0%)
hypomagnesemia	4/40 (10%)		4/23 (17.4%)		2/6 (33.3%)
hyponatremia	3/40 (7.5%)		2/23 (8.7%)		1/6 (16.7%)
Musculoskeletal and connective tissue disorders
arthralgia	2/40 (5%)		1/23 (4.3%)		0/6 (0%)
back pain	2/40 (5%)		2/23 (8.7%)		1/6 (16.7%)
musculoskeletal chest pain	8/40 (20%)		2/23 (8.7%)		0/6 (0%)
myalgia	2/40 (5%)		1/23 (4.3%)		0/6 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
cancer pain	3/40 (7.5%)		0/23 (0%)		0/6 (0%)
Nervous system disorders
dizziness	2/40 (5%)		2/23 (8.7%)		2/6 (33.3%)
dysgeusia	7/40 (17.5%)		3/23 (13%)		0/6 (0%)
Headache	5/40 (12.5%)		0/23 (0%)		2/6 (33.3%)
neurophaty peripheral	7/40 (17.5%)		3/23 (13%)		3/6 (50%)
peropheral sensory neuropathy	1/40 (2.5%)		3/23 (13%)		0/6 (0%)
Psychiatric disorders
anxiety	4/40 (10%)		3/23 (13%)		0/6 (0%)
insomnia	2/40 (5%)		3/23 (13%)		3/6 (50%)
Renal and urinary disorders
renal failure	1/40 (2.5%)		2/23 (8.7%)		1/6 (16.7%)
Respiratory, thoracic and mediastinal disorders
cough	7/40 (17.5%)		11/23 (47.8%)		5/6 (83.3%)
dyspnea	9/40 (22.5%)		8/23 (34.8%)		3/6 (50%)
epistaxis	1/40 (2.5%)		2/23 (8.7%)		1/6 (16.7%)
hiccups	5/40 (12.5%)		4/23 (17.4%)		2/6 (33.3%)
oropharyngeal pain	2/40 (5%)		0/23 (0%)		0/6 (0%)
pulmonary embolism	2/40 (5%)		0/23 (0%)		0/6 (0%)
rhinitis allergic	2/40 (5%)		0/23 (0%)		0/6 (0%)
rhinorrhea	1/40 (2.5%)		3/23 (13%)		0/6 (0%)
Skin and subcutaneous tissue disorders
alopecia	2/40 (5%)		2/23 (8.7%)		0/6 (0%)
hyperhidrosis	2/40 (5%)		1/23 (4.3%)		0/6 (0%)
night sweats	2/40 (5%)		1/23 (4.3%)		2/6 (33.3%)
pruritus	2/40 (5%)		1/23 (4.3%)		2/6 (33.3%)
rash	9/40 (22.5%)		1/23 (4.3%)		2/6 (33.3%)
Vascular disorders
hypertension	5/40 (12.5%)		0/23 (0%)		2/6 (33.3%)
phlebitis	2/40 (5%)		0/23 (0%)		1/6 (16.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.