To Immunize Patients With Extensive Stage SCLC Combined With Chemo With or Without All Trans Retinoic Acid

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00617409
• Collaborator: (none)
• Enrollment: 69
• Location: 1
• Arms: 3
• Actual Duration (Months): 136
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose of this research study is to test a tumor (cancer) vaccine given along with chemotherapy to determine if this vaccine will increase the chances of the tumor shrinking and/or the amount of time that people who have this disease will live.

Condition or Disease	Intervention/Treatment	Phase
Small Cell Lung Cancer	Drug: Paclitaxel; Biological: Drug: Ad.p53-DC vaccines; Drug: All -trans Retinoic Acid (ATRA)	Phase 2

Detailed Description

After initial diagnosis patients will be treated with a standard platinum/etoposide regimen. This standard first-line chemotherapy may/will be administered to patients under the direction of their primary medical oncologist inside or outside of the Moffitt Cancer Center. Patients will receive the platinum drug on day 1 and etoposide on days 1-3 of each 21-day cycle for 4-6 cycles. Patients who have progressive disease (PD) at this point are changed to second line chemotherapy, and will not be eligible to participate in this clinical trial. Patients who achieve a complete response (CR), partial response (PR), or stable disease (SD) after standard first-line chemotherapy will be enrolled. Radiographic studies and tumor measurements are repeated 3-6 weeks after the last dose of chemotherapy (+/- PCI) and may be repeated after prophylactic cranial irradiation (PCI) at the discretion of the principal investigator (PI) and treating physician.

PCI will be permitted at the discretion of the treating oncologist(s). The initial radiation consultation and simulation should occur as soon as the final staging has occurred. Ideally, treatment should commence 1-2 weeks after final staging has been confirmed and will be administered in 10-15 fractions over a 2-3 week period, as recommended by the treating radiation oncologist. Although steroid use is not prohibited, it is recommended and preferred that they not be used during PCI (steroids will have to be discontinued ≥ 2 weeks before first vaccination). PCI can also be considered between vaccines #4 and #5 or vaccine #5 and #6 in those patients eligible for the second course of vaccinations. Systemic dose of steroids will NOT be allowed in these cases unless strictly necessary and after discussion with the PI.

Patients who achieve CR, PR or SD after the completion of first line chemotherapy +/- PCI will be screened for initial registration. Screening tests and procedures will be performed approximately 4-6 weeks after the completion of first line chemotherapy or 6-9 weeks after completion of PCI. Ideally, screening should be completed 1-2 weeks prior to leukopheresis.

Patients who successfully complete the screening exams for initial registration will be randomized into one of three study arms.

Study Design

• Study Type: Interventional
• Actual Enrollment: 69 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase II Trial Using Dendritic Cells Transduced With an Adenoviral Vector Containing the p53 Gene to Immunize Patients With Extensive Stage Small Cell Lung Cancer in Combination With Chemotherapy With or Without All Trans Retinoic Acid
• Actual Study Start Date: Oct 2, 2007
• Actual Primary Completion Date: Sep 21, 2015
• Actual Study Completion Date: Jan 31, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Standard of Care Arm A - Active Comparator: Observation (Standard of Care) + Second Line Chemotherapy	Drug: Paclitaxel; All groups wil receive paclitaxel as second line chemotherapy if their cancer spreads. At any point when a patient develops evidence of progressive disease, the patient will be treated with second-line chemotherapy. Paclitaxel will be given at a dose of 200 mg/m² on day 1 of 21 day cycles.; Other Names: Antitumor agent Chemotherapy
Experimental: Ad.p53-DC Vaccines Arm B - Experimental: Ad.p53-DC vaccines + Second Line Chemotherapy	Drug: Paclitaxel; All groups wil receive paclitaxel as second line chemotherapy if their cancer spreads. At any point when a patient develops evidence of progressive disease, the patient will be treated with second-line chemotherapy. Paclitaxel will be given at a dose of 200 mg/m² on day 1 of 21 day cycles.; Other Names: Antitumor agent Chemotherapy ; Biological: Drug: Ad.p53-DC vaccines; Patients randomized to Arm B will receive vaccinations on 3 occasions, at 2 week intervals. 1-5x106 p53 positive DCs in 1 ml will be injected intradermally into 4 separate sites (0.25 ml injected at each site), in bilateral proximal upper and lower extremities (in the regions of the axillary and inguinal nodal basins). Patients will be restaged approximately 2-3 weeks after vaccine # 3 (first vaccine course). If patients show no sign of disease progression at restaging, then a second leukopheresis will be performed. Patients will then be vaccinated 3 more times (second vaccine course) at 4-week intervals, for a total of 6 possible vaccines. Restaging will occur 2-4 weeks after completing the second vaccine course. Patients in Arm C will receive vaccines at the same dose and schedule as described for patients in Arm B. In addition, they will receive 150 mg/m² of ATRA for 3 days prior to each vaccine administration (followed by vaccine administration on the fourth day).; Other Names: INGN 225
Experimental: Ad.p53-DC Vaccines + ATRA Arm C - Experimental: Ad.p53-DC vaccines + All -trans Retinoic Acid (ATRA) + Second Line Chemotherapy	Drug: Paclitaxel; All groups wil receive paclitaxel as second line chemotherapy if their cancer spreads. At any point when a patient develops evidence of progressive disease, the patient will be treated with second-line chemotherapy. Paclitaxel will be given at a dose of 200 mg/m² on day 1 of 21 day cycles.; Other Names: Antitumor agent Chemotherapy ; Biological: Drug: Ad.p53-DC vaccines; Patients randomized to Arm B will receive vaccinations on 3 occasions, at 2 week intervals. 1-5x106 p53 positive DCs in 1 ml will be injected intradermally into 4 separate sites (0.25 ml injected at each site), in bilateral proximal upper and lower extremities (in the regions of the axillary and inguinal nodal basins). Patients will be restaged approximately 2-3 weeks after vaccine # 3 (first vaccine course). If patients show no sign of disease progression at restaging, then a second leukopheresis will be performed. Patients will then be vaccinated 3 more times (second vaccine course) at 4-week intervals, for a total of 6 possible vaccines. Restaging will occur 2-4 weeks after completing the second vaccine course. Patients in Arm C will receive vaccines at the same dose and schedule as described for patients in Arm B. In addition, they will receive 150 mg/m² of ATRA for 3 days prior to each vaccine administration (followed by vaccine administration on the fourth day).; Other Names: INGN 225 ; Drug: All -trans Retinoic Acid (ATRA); The patients in Arm C will receive vaccines at the same dose and schedule as described for patients in Arm B. In addition, they will receive 150 mg/m² of ATRA for 3 days prior to each vaccine administration (followed by vaccine administration on the fourth day).; Other Names: tretinoin Vesanoid INGN 225

Outcome Measures

Primary Outcome Measures

1. Tumor Response Rate (RR) [12 months]

   Overall Response: Complete Response (CR) + Partial Response (PR) + Stable Disease (SD). Efficacy of second line chemotherapy (single agent paclitaxel) after progression following the dendritic cell(DC)-based p53 vaccine (Ad.p53-DC vaccine), with (Arm C). To estimate the objective tumor response rate for each treatment group. Tumor response to be assessed via radiographic imaging after every 2 cycles of chemotherapy (paclitaxel). CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease (PD), taking as reference the smallest sum LD since the treatment started. PD: At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Secondary Outcome Measures

1. Overall Survival (OS) [Up to 24 months]

   To evaluate the survival of all patients enrolled on an intent-to-treat basis. Overall survival per treatment arm.

Eligibility Criteria

Criteria

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

Inclusion Criteria at the time of initial registration:

• Patients must have a histological confirmed diagnosis of Small Cell Lung Cancer (SCLC)

• Must have extensive stage SCLC

• Must have completed first line chemotherapy: 4-6 cycles of a standard platinum/etoposide regimen and PCI if chosen at the discretion of the treating Oncologist

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

• Acceptable (adequate) organ function including:

• White blood count (WBC) >2,500/mm³ and Absolute neutrophil count (ANC) >1,200/mm³

• Platelets > 75,000/mm³

• Hematocrit > 24% OR Hemoglobin ≥8.5g/dl

• Bilirubin < 2.0 mg/dl

• Creatinine < 2.0 mg/dl

• Aspartic transaminase (AST/SGOT) ≤2 x upper limit of normal (ULN)

• Alkaline phosphatase ≤3 x ULN

• Patients must have achieved responsive or non-progressive disease status (stable disease [SD], partial response [PR], or complete response [CR]) assessed 4-6 weeks after the last cycle of first line chemotherapy. SD, PR or CR may be confirmed after completion of prophylactic cranial irradiation (PCI) at the discretion of the principal investigator (PI) after discussion with the treating oncologist.

• Males and Females of reproductive potential must agree to use effective contraception during the study and for at least 4 weeks after the last dose of ATRA. Patients are instructed and agree to notify the principal investigator should a pregnancy occur for themselves or their partner.

• Willing and able to sign written informed consent and be able to comply with the study protocol for the duration of the study

Exclusion Criteria at the time of initial registration:

• Patients with severe, uncontrolled intercurrent illness or infection

• Anticipated requirement for systemic chronic steroid use at the time of vaccination, unless specifically indicated for dose supplementation or replacement of established corticosteroid insufficiency

• Receiving systemic doses of corticosteroids should have them discontinued ≥ 2 weeks prior to starting vaccination (this include patients receiving steroids with PCI). Inhaled steroids should also be discontinued if at all possible. Chronic, stable doses of inhaled steroids for the treatment of chronic obstructive pulmonary disease (COPD), etc. are allowed if in the opinion of the treating physician(s) they cannot be stopped.

• Any pre-existing immunodeficiency condition, or a known history of human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C

• Uncontrolled and/or symptomatic central nervous system (CNS) metastasis

• Pregnant or lactating women. A pregnancy test-serum Beta human chorionic gonadotropin (bHCG) will be obtained during the screening process.

• Have received any chemotherapy other than the first line chemotherapy specified in the study protocol: standard platinum/etoposide regimen

• Have received any prior investigational drugs including immunotherapy, gene therapy, hormone therapy, biologic therapy for treatment of SCLC

• Any known pre-existing autoimmune disorder

• History of a second malignancy within the previous 3 years. Exceptions include: non-melanoma skin cancers, any in-situ carcinomas and successfully treated early stage malignancies without evidence of recurrence for > 18 months.

• Have not recovered from any chemotherapy-related or other therapy-related toxicity at study entry

• Have had major surgery without full recovery or major surgery within 3 weeks of the start of vaccine treatment

• Patients with other significant diseases or disorders that, in the Investigator's opinion, would exclude them from the study

Pre-Pheresis Criteria:

• Patients must have had a successful harvest of peripheral blood mononuclear cell (PBMC) with leukopheresis at least 6-10 weeks after chemotherapy.

• ECOG performance status of 0-2

• The last dose of first line chemotherapy must have been administered at least 4 weeks prior to the first vaccine administration.

• Patients who received radiation therapy: last dose of radiation must have been completed at least 2 weeks prior to the first vaccine administration and the patient must have recovered from the toxic effects of the treatment prior to study enrollment (except for alopecia)

• Patients who received steroid therapy: last steroid dose must have been given at least 2 weeks prior to the first vaccine administration

• Adequate organ function:

• WBC > 2,500/mm³ and ANC >1,200/mm³

• Platelets > 75,000/mm³

• Hematocrit > 25%

• Hemoglobin ≥9g/dl

• Bilirubin < 2.0 mg/dl

• Creatinine < 2.0 mg/dL

• AST/SGOT ≤ 2 x ULN

• Alkaline phosphatase < 3 x ULN

• Patients must have signed informed consent at initial registration.

• HLA-A*0201 Testing as determined by flow cytometry followed by molecular analysis of a peripheral blood specimen, however this result will not be an inclusion criterion

Pre-Paclitaxel Eligibility:

• Progressive disease after observation (Arm A) or vaccinations (Arms B and C)

• ECOG performance status of 0-2

• Adequate organ function:

• WBC > 2,500/mm³ and ANC >1,200/mm³

• Platelets > 75,000/mm³

• Hematocrit > 25%

• Hemoglobin ≥9g/dl

• Bilirubin < 2.0 mg/dl

• Creatinine < 2.0 mg/dL

• AST/SGOT ≤ 2 x ULN

• Alkaline phosphatase < 3 x ULN

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida	United States	33612

Sponsors and Collaborators

• H. Lee Moffitt Cancer Center and Research Institute

Investigators

• Principal Investigator: Scott Antonia, M.D., H. Lee Moffitt Cancer Center and Research Institute

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Moffitt Cancer Center Clinical Trials website

Publications

None provided.

• Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
• ClinicalTrials.gov Identifier: NCT00617409
• Other Study ID Numbers: MCC-15206; 105790; 0147NE; 0705-857; NCT00618891
• First Posted: Feb 18, 2008
• Last Update Posted: Nov 8, 2019
• Last Verified: Nov 1, 2019

• Keywords provided by H. Lee Moffitt Cancer Center and Research Institute: SCLC; vaccine; immunize
• Additional relevant MeSH terms: Lung Neoplasms; Small Cell Lung Carcinoma; Paclitaxel; Tretinoin

Study Results

Participant Flow

Arm/Group Title	Standard of Care	Ad.p53-DC Vaccines	Ad.p53-DC Vaccines + ATRA
Arm/Group Description	Arm A - Active Comparator: Observation (Standard of Care) + Second Line Chemotherapy	Arm B - Experimental: Ad.p53-DC vaccines + Second Line Chemotherapy	Arm C - Experimental: Ad.p53-DC vaccines + All -trans Retinoic Acid (ATRA) + Second Line Chemo
Period Title: Overall Study
STARTED	18	20	31
COMPLETED	2	2	4
NOT COMPLETED	16	18	27

Baseline Characteristics

Arm/Group Title	Arm A - Active Comparator	Arm B - Experimental	Arm C - Experimental	Total
Arm/Group Description	Active Comparator: Observation (Standard of Care) + Second Line Chemotherapy	Experimental: Ad.p53-DC vaccines + Second Line Chemotherapy	Experimental: Ad.p53-DC vaccines + ATRA + Second Line Chemo	Total of all reporting groups
Overall Participants	18	20	31	69
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	10 55.6%	12 60%	19 61.3%	41 59.4%
>=65 years	8 44.4%	8 40%	12 38.7%	28 40.6%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	63	63	62.45	62.75
Sex: Female, Male (Count of Participants)
Female	7 38.9%	13 65%	16 51.6%	36 52.2%
Male	11 61.1%	7 35%	15 48.4%	33 47.8%
Region of Enrollment (participants) [Number]
United States	18 100%	20 100%	31 100%	69 100%

Outcome Measures

1. Primary Outcome

Title	Tumor Response Rate (RR)
Description	Overall Response: Complete Response (CR) + Partial Response (PR) + Stable Disease (SD). Efficacy of second line chemotherapy (single agent paclitaxel) after progression following the dendritic cell(DC)-based p53 vaccine (Ad.p53-DC vaccine), with (Arm C). To estimate the objective tumor response rate for each treatment group. Tumor response to be assessed via radiographic imaging after every 2 cycles of chemotherapy (paclitaxel). CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease (PD), taking as reference the smallest sum LD since the treatment started. PD: At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

All participants.

Arm/Group Title	Standard of Care	Ad.p53-DC Vaccines	Ad.p53-DC Vaccines + ATRA
Arm/Group Description	Arm A - Active Comparator: Observation (Standard of Care) + Second Line Chemotherapy	Arm B - Experimental: Ad.p53-DC vaccines + Second Line Chemotherapy	Arm C - Experimental: Ad.p53-DC vaccines + All -trans Retinoic Acid (ATRA) + Second Line Chemo
Measure Participants	18	20	31
Overall Response	8 44.4%	6 30%	12 38.7%
Progressive Disease	1 5.6%	5 25%	6 19.4%

2. Secondary Outcome

Title	Overall Survival (OS)
Description	To evaluate the survival of all patients enrolled on an intent-to-treat basis. Overall survival per treatment arm.
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

All participants.

Arm/Group Title	Standard of Care	Ad.p53-DC Vaccines	Ad.p53-DC Vaccines + ATRA
Arm/Group Description	Arm A - Active Comparator: Observation (Standard of Care) + Second Line Chemotherapy	Arm B - Experimental: Ad.p53-DC vaccines + Second Line Chemotherapy	Arm C - Experimental: Ad.p53-DC vaccines + ATRA + Second Line Chemo
Measure Participants	18	20	31
Median (95% Confidence Interval) [months]	12.17	6.32	6.20

Adverse Events

Time Frame	6 years, 6 months
Arm/Group Title	Arm A - Active Comparator		Arm B - Experimental		Arm C - Experimental
Arm/Group Description	Active Comparator: Observation (Standard of Care) + Second Line Chemotherapy		Experimental: Ad.p53-DC vaccines + Second Line Chemotherapy		Experimental: Ad.p53-DC vaccines + ATRA + Second Line Chemo
All Cause Mortality
	Arm A - Active Comparator		Arm B - Experimental		Arm C - Experimental
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm A - Active Comparator		Arm B - Experimental		Arm C - Experimental
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/18 (38.9%)		9/20 (45%)		12/31 (38.7%)
Blood and lymphatic system disorders
Blood and lymphatic system disorders - Other, Leukopenia/Anemia	0/18 (0%)	0	1/20 (5%)	1	0/31 (0%)	0
Cardiac disorders
Cardiac ischemia/infarction	0/18 (0%)	0	0/20 (0%)	0	1/31 (3.2%)	1
Gastrointestinal disorders
Dehydration	0/18 (0%)	0	0/20 (0%)	0	1/31 (3.2%)	1
Dysphagia	0/18 (0%)	0	0/20 (0%)	0	1/31 (3.2%)	1
Mucositis/stomatitis (clinical exam) - Oral cavity	0/18 (0%)	0	0/20 (0%)	0	2/31 (6.5%)	2
Vomiting	0/18 (0%)	0	1/20 (5%)	1	0/31 (0%)	0
General disorders
Death NOS	0/18 (0%)	0	3/20 (15%)	3	5/31 (16.1%)	5
Fever (in the absence of neutropenia)	0/18 (0%)	0	1/20 (5%)	1	0/31 (0%)	0
Pain - Chest wall	0/18 (0%)	0	0/20 (0%)	0	1/31 (3.2%)	1
Pain - Chest/thorax NOS	0/18 (0%)	0	1/20 (5%)	1	0/31 (0%)	0
Rigors/chills	0/18 (0%)	0	1/20 (5%)	1	0/31 (0%)	0
Infections and infestations
Febrile neutopenia	1/18 (5.6%)	1	0/20 (0%)	0	1/31 (3.2%)	1
Infection with Grade 3 or 4 neutrophils - Mucosa	0/18 (0%)	0	0/20 (0%)	0	1/31 (3.2%)	1
Infection with normal ANC or Grade 1 or 2 neutrophils - Lung (pneumonia)	0/18 (0%)	0	1/20 (5%)	1	0/31 (0%)	0
Investigations
Leukocytes (total WBC) - low	0/18 (0%)	0	0/20 (0%)	0	1/31 (3.2%)	1
Platelets - low	0/18 (0%)	0	0/20 (0%)	0	1/31 (3.2%)	1
Musculoskeletal and connective tissue disorders
Pain - Bone	1/18 (5.6%)	1	0/20 (0%)	0	0/31 (0%)	0
Pain - Extremity-limb	0/18 (0%)	0	0/20 (0%)	0	1/31 (3.2%)	1
Nervous system disorders
Neuropathy: motor	0/18 (0%)	0	0/20 (0%)	0	1/31 (3.2%)	1
Pain - Head/headache	1/18 (5.6%)	1	1/20 (5%)	1	0/31 (0%)	0
Seizure	2/18 (11.1%)	2	0/20 (0%)	0	0/31 (0%)	0
Psychiatric disorders
Confusion	0/18 (0%)	0	0/20 (0%)	0	2/31 (6.5%)	2
Suicide attempt	1/18 (5.6%)	1	0/20 (0%)	0	0/31 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	0/18 (0%)	0	1/20 (5%)	1	0/31 (0%)	0
Dyspnea	0/18 (0%)	0	6/20 (30%)	7	3/31 (9.7%)	3
Pneumonitis/pulmonary infiltrates	0/18 (0%)	0	1/20 (5%)	1	0/31 (0%)	0
Pulmonary/Upper Respiratory - Other	0/18 (0%)	0	1/20 (5%)	1	1/31 (3.2%)	1
Pulmonary/Upper Respiratory - Other, COPD	0/18 (0%)	0	0/20 (0%)	0	0/31 (0%)	0
Pulmonary/Upper Respiratory - Other, Pneumonia	0/18 (0%)	0	1/20 (5%)	1	0/31 (0%)	0
Vascular disorders
Superior vena cava syndrome	0/18 (0%)	0	0/20 (0%)	0	1/31 (3.2%)	1
Thrombosis/embolism (vascular access-related)	0/18 (0%)	0	0/20 (0%)	0	1/31 (3.2%)	1
Thrombosis/thrombus/embolism	0/18 (0%)	0	1/20 (5%)	1	0/31 (0%)	0
Vessel injury-artery - Other NOS	1/18 (5.6%)	1	0/20 (0%)	0	0/31 (0%)	0
Other (Not Including Serious) Adverse Events
	Arm A - Active Comparator		Arm B - Experimental		Arm C - Experimental
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/18 (88.9%)		17/20 (85%)		31/31 (100%)
Blood and lymphatic system disorders
Edema: limb	1/18 (5.6%)	1	1/20 (5%)	1	1/31 (3.2%)	1
Hemolysis (e.g., immune hemolytic anemia, drugrelated hemolysis)	1/18 (5.6%)	1	1/20 (5%)	1	2/31 (6.5%)	2
Leukocytes (total WBC) - Low	1/18 (5.6%)	1	2/20 (10%)	6	5/31 (16.1%)	11
Lymphopenia	1/18 (5.6%)	1	0/20 (0%)	0	3/31 (9.7%)	9
Neutrophils/granulocytes (ANC/AGC) - Low	1/18 (5.6%)	1	1/20 (5%)	1	0/31 (0%)	0
Cardiac disorders
Supraventricular and nodal arrhythmia - Sinus tachycardia	1/18 (5.6%)	1	0/20 (0%)	0	0/31 (0%)	0
Ear and labyrinth disorders
Auditory/Ear - Other, Hearing loss	1/18 (5.6%)	1	0/20 (0%)	0	0/31 (0%)	0
Eye disorders
Ocular/Visual - Other, Keratotic lesion-left side	1/18 (5.6%)	1	0/20 (0%)	0	0/31 (0%)	0
Ocular/Visual - Other, Right sided ptosis	1/18 (5.6%)	1	0/20 (0%)	0	0/31 (0%)	0
Vision-blurred vision	1/18 (5.6%)	1	2/20 (10%)	2	2/31 (6.5%)	2
Gastrointestinal disorders
Anorexia	7/18 (38.9%)	11	5/20 (25%)	6	12/31 (38.7%)	15
Constipation	1/18 (5.6%)	1	4/20 (20%)	4	5/31 (16.1%)	6
Dehydration	0/18 (0%)	0	1/20 (5%)	1	0/31 (0%)	0
Diarrhea	1/18 (5.6%)	3	2/20 (10%)	2	9/31 (29%)	10
Dry mouth/salivary gland (xerostomia)	0/18 (0%)	0	0/20 (0%)	0	2/31 (6.5%)	2
Dysphagia	2/18 (11.1%)	3	0/20 (0%)	0	2/31 (6.5%)	2
Esophagitis	3/18 (16.7%)	3	0/20 (0%)	0	1/31 (3.2%)	1
Flatulance	0/18 (0%)	0	1/20 (5%)	1	0/31 (0%)	0
Gastrointestinal - Other, Decrease color in stools	1/18 (5.6%)	1	0/20 (0%)	0	0/31 (0%)	0
Gastrointestinal - Other, GI virus	0/18 (0%)	0	1/20 (5%)	1	0/31 (0%)	0
Gastrointestinal - Other, Increased burping	1/18 (5.6%)	1	0/20 (0%)	0	0/31 (0%)	0
Heartburn/dyspepsia	0/18 (0%)	0	2/20 (10%)	3	2/31 (6.5%)	2
Mucositis/stomatitis (clinical exam) - Oral cavity	0/18 (0%)	0	1/20 (5%)	1	1/31 (3.2%)	1
Mucositis/stomatitis (functional/symptomatic) - Oral cavity	0/18 (0%)	0	1/20 (5%)	1	0/31 (0%)	0
Nausea	3/18 (16.7%)	4	3/20 (15%)	3	14/31 (45.2%)	22
Pain - Absomen NOS	1/18 (5.6%)	1	2/20 (10%)	3	4/31 (12.9%)	5
Pain - Esophagus	1/18 (5.6%)	1	0/20 (0%)	0	0/31 (0%)	0
Pain - Other, Pain at distal margins	0/18 (0%)	0	1/20 (5%)	1	0/31 (0%)	0
Pain - Stomach	1/18 (5.6%)	2	0/20 (0%)	0	0/31 (0%)	0
Taste alteration (dysgeusia)	1/18 (5.6%)	1	0/20 (0%)	0	1/31 (3.2%)	1
Vomiting	1/18 (5.6%)	3	1/20 (5%)	1	9/31 (29%)	13
General disorders
Fatigue	8/18 (44.4%)	12	13/20 (65%)	19	22/31 (71%)	29
Fever (in the absence of neutropenia)	2/18 (11.1%)	2	1/20 (5%)	1	1/31 (3.2%)	1
Flu-like syndrome	0/18 (0%)	0	0/20 (0%)	0	2/31 (6.5%)	2
Pain - Chest/thorax NOS	0/18 (0%)	0	1/20 (5%)	1	1/31 (3.2%)	1
Pain - Face	0/18 (0%)	0	0/20 (0%)	0	2/31 (6.5%)	4
Pain - Other, Upper quadrant	1/18 (5.6%)	1	0/20 (0%)	0	0/31 (0%)	0
Pain - Pain NOS	0/18 (0%)	0	1/20 (5%)	1	0/31 (0%)	0
Rigors/chills	1/18 (5.6%)	1	1/20 (5%)	1	0/31 (0%)	0
Sweating (diaphoresis)	1/18 (5.6%)	1	2/20 (10%)	2	2/31 (6.5%)	3
Immune system disorders
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)	1/18 (5.6%)	1	0/20 (0%)	0	3/31 (9.7%)	3
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils - Urinary tract NOS	0/18 (0%)	0	1/20 (5%)	1	0/31 (0%)	0
Infection with unknown ANC - Lung (pneumonia)	0/18 (0%)	0	2/20 (10%)	2	1/31 (3.2%)	1
Investigations
Bilirubin (hyperbilirubinemia)	0/18 (0%)	0	0/20 (0%)	0	2/31 (6.5%)	2
Creatinine - High	0/18 (0%)	0	1/20 (5%)	1	2/31 (6.5%)	2
Hemoglobin - Low	3/18 (16.7%)	3	4/20 (20%)	5	6/31 (19.4%)	15
Lipase increased	1/18 (5.6%)	1	0/20 (0%)	0	0/31 (0%)	0
Metabolic/Laboratory - Other, Elevated AST	2/18 (11.1%)	2	0/20 (0%)	0	3/31 (9.7%)	3
Platelets - Low	1/18 (5.6%)	1	3/20 (15%)	3	6/31 (19.4%)	14
Weight loss	4/18 (22.2%)	4	1/20 (5%)	1	3/31 (9.7%)	3
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia)	1/18 (5.6%)	1	0/20 (0%)	0	3/31 (9.7%)	3
Alkaline phosphatase	2/18 (11.1%)	3	0/20 (0%)	0	4/31 (12.9%)	7
Alkalosis (metabolic or respiratory)	1/18 (5.6%)	1	0/20 (0%)	0	0/31 (0%)	0
ALT, SGPT (serum glutamic pyruvic transaminase) - High	1/18 (5.6%)	1	1/20 (5%)	1	4/31 (12.9%)	5
Amylase	1/18 (5.6%)	1	0/20 (0%)	0	0/31 (0%)	0
Calcium, serum-high (hypercalcemia)	0/18 (0%)	0	1/20 (5%)	1	2/31 (6.5%)	2
Glucose, serum-high (hyperglycemia)	4/18 (22.2%)	4	5/20 (25%)	5	8/31 (25.8%)	18
Magnesium, serum-low (hypomagnesemia)	0/18 (0%)	0	1/20 (5%)	1	5/31 (16.1%)	8
Metabolic/Laboratory - Other, Hyperlipidemia	1/18 (5.6%)	1	0/20 (0%)	0	0/31 (0%)	0
Metabolic/Laboratory - Other, Decreased HDL	1/18 (5.6%)	1	0/20 (0%)	0	0/31 (0%)	0
Metabolic/Laboratory - Other, Decreased protein	1/18 (5.6%)	1	0/20 (0%)	0	0/31 (0%)	0
Metabolic/Laboratory - Other, High total protein	1/18 (5.6%)	1	0/20 (0%)	0	0/31 (0%)	0
Metabolic/Laboratory - Other, Hyperglycemia	0/18 (0%)	0	1/20 (5%)	1	0/31 (0%)	0
Metabolic/Laboratory - Other, Increased ALT	1/18 (5.6%)	2	0/20 (0%)	0	1/31 (3.2%)	2
Phosphate, serum-low (hypophosphatemia)	0/18 (0%)	0	1/20 (5%)	1	0/31 (0%)	0
Potassium, serum-high (hyperkalemia)	1/18 (5.6%)	1	1/20 (5%)	1	2/31 (6.5%)	3
Potassium, serum-low (hypokalemia)	0/18 (0%)	0	0/20 (0%)	0	2/31 (6.5%)	2
Sodium, serum-low (hyponatremia)	0/18 (0%)	0	2/20 (10%)	4	6/31 (19.4%)	9
Musculoskeletal and connective tissue disorders
Arthritis (non-septic)	1/18 (5.6%)	1	0/20 (0%)	0	0/31 (0%)	0
Muscle weakness, generalized or specific area (not due to neuropathy) - Extraocular	1/18 (5.6%)	1	0/20 (0%)	0	1/31 (3.2%)	1
Muscle weakness, generalized or specific area (not due to neuropathy) - Extremitylower	0/18 (0%)	0	1/20 (5%)	1	1/31 (3.2%)	1
Muscle weakness, generalized or specific area (not due to neuropathy) - Whole body/generalized	2/18 (11.1%)	2	2/20 (10%)	2	1/31 (3.2%)	1
Pain - Back	2/18 (11.1%)	3	5/20 (25%)	7	5/31 (16.1%)	5
Pain - Bone	0/18 (0%)	0	0/20 (0%)	0	7/31 (22.6%)	10
Pain - Chest wall	2/18 (11.1%)	2	3/20 (15%)	3	2/31 (6.5%)	2
Pain - Extremity-limb	3/18 (16.7%)	4	2/20 (10%)	3	5/31 (16.1%)	8
Pain - Joint	2/18 (11.1%)	2	0/20 (0%)	0	4/31 (12.9%)	4
Pain - Muscle	2/18 (11.1%)	3	0/20 (0%)	0	6/31 (19.4%)	6
Pain - Other, Flank	1/18 (5.6%)	1	0/20 (0%)	0	0/31 (0%)	0
Pain - Other, Hip	1/18 (5.6%)	1	0/20 (0%)	0	0/31 (0%)	0
Pain - Other, Rib/Rib cage	2/18 (11.1%)	2	0/20 (0%)	0	0/31 (0%)	0
Pain - Other, Shoulder	1/18 (5.6%)	1	0/20 (0%)	0	2/31 (6.5%)	3
Nervous system disorders
Ataxia (incoordination)	0/18 (0%)	0	0/20 (0%)	0	2/31 (6.5%)	2
Dizziness	4/18 (22.2%)	4	1/20 (5%)	1	3/31 (9.7%)	3
Memory Impairment	1/18 (5.6%)	1	0/20 (0%)	0	1/31 (3.2%)	1
Neurology - Other, Numbness in lower legs and feet	1/18 (5.6%)	2	0/20 (0%)	0	0/31 (0%)	0
Neuropathy: cranial - CN IX Motor-pharynx; Sensory-ear, pharynx, tongue	0/18 (0%)	0	0/20 (0%)	0	2/31 (6.5%)	2
Neuropathy: cranial - CN VIII Hearing and balance	1/18 (5.6%)	1	0/20 (0%)	0	0/31 (0%)	0
Neuropathy: motor	0/18 (0%)	0	1/20 (5%)	1	1/31 (3.2%)	1
Neuropathy: sensory	3/18 (16.7%)	4	3/20 (15%)	4	9/31 (29%)	14
Pain - Head/headache	3/18 (16.7%)	4	4/20 (20%)	4	22/31 (71%)	65
Psychiatric disorders
Confusion	1/18 (5.6%)	1	1/20 (5%)	1	0/31 (0%)	0
Insomnia	1/18 (5.6%)	2	2/20 (10%)	2	4/31 (12.9%)	5
Mental status	1/18 (5.6%)	1	0/20 (0%)	0	0/31 (0%)	0
Mood alteration - Anxiety	2/18 (11.1%)	2	1/20 (5%)	1	1/31 (3.2%)	1
Mood alteration - Depression	1/18 (5.6%)	1	2/20 (10%)	2	1/31 (3.2%)	1
Renal and urinary disorders
Incontinence, urinary	1/18 (5.6%)	1	0/20 (0%)	0	1/31 (3.2%)	1
Obstruction, GU - Ureter	1/18 (5.6%)	1	0/20 (0%)	0	0/31 (0%)	0
Urine color change	1/18 (5.6%)	1	0/20 (0%)	0	0/31 (0%)	0
Reproductive system and breast disorders
Pain - Breast	1/18 (5.6%)	1	0/20 (0%)	0	0/31 (0%)	0
Pain - Pelvis	1/18 (5.6%)	1	0/20 (0%)	0	0/31 (0%)	0
Respiratory, thoracic and mediastinal disorders
Bronchospasm, wheezing	2/18 (11.1%)	2	1/20 (5%)	1	0/31 (0%)	0
Cough	8/18 (44.4%)	10	9/20 (45%)	10	11/31 (35.5%)	16
Dyspnea	9/18 (50%)	11	11/20 (55%)	17	14/31 (45.2%)	20
Hemorrhage/Bleeding - Other, Hemoptysis	0/18 (0%)	0	1/20 (5%)	1	0/31 (0%)	0
Hypoxia	0/18 (0%)	0	1/20 (5%)	1	0/31 (0%)	0
Nasal cavity/paranasal sinus reactions	1/18 (5.6%)	1	1/20 (5%)	1	0/31 (0%)	0
Pain - Pleura	0/18 (0%)	0	1/20 (5%)	1	0/31 (0%)	0
Pneumonitis/pulmonary infiltrates	1/18 (5.6%)	1	0/20 (0%)	0	0/31 (0%)	0
Pulmonary/Upper Respiratory - Other, Wheezing	1/18 (5.6%)	1	0/20 (0%)	0	0/31 (0%)	0
Pulmonary/Upper Respiratory - Other, Absent breath sounds-right base	1/18 (5.6%)	1	0/20 (0%)	0	0/31 (0%)	0
Pulmonary/Upper Respiratory - Other, Congestion	1/18 (5.6%)	1	0/20 (0%)	0	0/31 (0%)	0
Voice changes/dysarthria (e.g., hoarseness, loss or alteration in voice, laryngitis)	1/18 (5.6%)	1	0/20 (0%)	0	0/31 (0%)	0
Skin and subcutaneous tissue disorders
Bruising (in absence of Grade 3 or 4 thrombocytopenia)	0/18 (0%)	0	1/20 (5%)	1	0/31 (0%)	0
Dermatology/Skin - Other, erythema- chest wall and scalp	1/18 (5.6%)	1	0/20 (0%)	0	0/31 (0%)	0
Dermatology/Skin - Other, Tightness of skin on hands	1/18 (5.6%)	1	0/20 (0%)	0	0/31 (0%)	0
Dry skin	1/18 (5.6%)	1	0/20 (0%)	0	6/31 (19.4%)	11
Hair loss/alopecia (scalp or body)	3/18 (16.7%)	5	3/20 (15%)	4	7/31 (22.6%)	11
Hyperpigmentation	1/18 (5.6%)	1	0/20 (0%)	0	0/31 (0%)	0
Injection site reaction/extravasation changes	0/18 (0%)	0	3/20 (15%)	4	4/31 (12.9%)	4
Pain - Scalp	0/18 (0%)	0	1/20 (5%)	1	0/31 (0%)	0
Pruritus/itching	1/18 (5.6%)	1	2/20 (10%)	2	5/31 (16.1%)	6
Rash/desquamation	0/18 (0%)	0	0/20 (0%)	0	3/31 (9.7%)	4
Rash: acne/acneiform	1/18 (5.6%)	1	1/20 (5%)	1	2/31 (6.5%)	4
Rash: dermatitis associated with radiation - Chemoradiation	1/18 (5.6%)	1	0/20 (0%)	0	0/31 (0%)	0
Rash: dermatitis associated with radiation - Radiation	1/18 (5.6%)	1	0/20 (0%)	0	1/31 (3.2%)	1
Rash: hand-foot skin reaction	0/18 (0%)	0	0/20 (0%)	0	2/31 (6.5%)	3
Skin breakdown/decubitus ulcer	2/18 (11.1%)	2	0/20 (0%)	0	0/31 (0%)	0
Vascular disorders
Hypertension	0/18 (0%)	0	1/20 (5%)	1	0/31 (0%)	0
Hypotension	1/18 (5.6%)	1	0/20 (0%)	0	0/31 (0%)	0
Vascular - Other, Chronic venous stasis in legs	1/18 (5.6%)	1	0/20 (0%)	0	0/31 (0%)	0

Limitations/Caveats

Protocol V.10.1, 04/11/2012: Arm A was closed due to lack of feasibility; Arm B was closed at the end of the first stage due to lack of efficacy.

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.