Temsirolimus + Weekly Paclitaxel + Carboplatin for Recurrent or Metastatic Head and Neck Squamous Cell Cancer (HNSCC)

• Sponsor: Memorial Sloan Kettering Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01016769
• Collaborator: NATL COMP CA NETWORK (Other), Pfizer (Industry)
• Enrollment: 48
• Locations: 5
• Arm: 1
• Actual Duration (Months): 103
• Patients Per Site: 9.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to find out the good and bad effects that occur when temsirolimus is added to standard chemotherapy with carboplatin and paclitaxel.

Condition or Disease	Intervention/Treatment	Phase
Squamous Cell Cancer; Head and Neck Cancer	Drug: Temsirolimus + Weekly Paclitaxel + Carboplatin	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 48 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/II Study of Temsirolimus + Weekly Paclitaxel + Carboplatin for Recurrent or Metastatic Head and Neck Squamous Cell Cancer (HNSCC)
• Actual Study Start Date: Nov 1, 2009
• Actual Primary Completion Date: Jun 1, 2018
• Actual Study Completion Date: Jun 1, 2018

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Temsirolimus + Weekly Paclitaxel + Carboplatin In Part 1 (Phase I) of the study, the primary endpoint is to establish the phase II recommended dose for the combination of temsirolimus + weekly paclitaxel + carboplatinPart 1 (Phase I) features a standard 3 + 3 phase I dose escalation design. Up to 3 dose levels are planned in the Phase I portion of the study. In Part 2 (Phase II) of the study, the primary endpoint is to determine the objective response rate (CR or PR) after two cycles (approximately 6 weeks) of treatment with the combination of temsirolimus + weekly paclitaxel + carboplatin as palliative therapy for recurrent or metastatic HNSCC. A two-stage design will be employed.

Drug: Temsirolimus + Weekly Paclitaxel + Carboplatin; Temsirolimus Per dose escalation scheme Level 1 (15 mg) 2 (20 mg) Level 3 (25 mg) IVPB 30 minutes weekly (3 weeks on, 1 week off) days 1 and 8. Paclitaxel 80 mg/m2 IVPB 1 hour weekly (2 weeks on, 1 week off) days 1 and 8. Carboplatin AUC 1.5 IVPB 30 minutes days 1 and 8. On Day 15 of each cycle, patients begin the rest week.

Outcome Measures

Primary Outcome Measures

1. Phase II Recommended Dose for the Combination of Temsirolimus + Weekly Paclitaxel + Carboplatin. [2 years]

2. To Determine the Objective Response Rate (CR or PR) After Two Cycles of Treatment With the Combination of Temsirolimus + Weekly Paclitaxel + Carboplatin as Palliative Therapy for Recurrent or Metastatic HNSCC [6 weeks]

   Evaluation of target lesions: Complete Response - disappearance of all target lesions Partial Response - at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter Progressive Disease - at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started, or the appearance of one of more new lesions Stable Disease - neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since the treatment started

Secondary Outcome Measures

1. Number of Participants Who Experienced Adverse Events [2 years]

   Safety will be assessed in terms of AEs according to CTCAE version 3.0

2. Median Overall Survival [2 years]

3. Number of Participants With Potential Molecular Markers of Resistance to mTOR Inhibition [2 years]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients must have microscopically confirmed head and neck squamous cell carcinoma (HNSCC), recurrent and/or metastatic.

• Confirmation of HNSCC may be obtained from the primary site or metastatic disease.

• Patients must be at least 18 years of age.

• Karnofsky Performance status must be ≥ 70%.

• Disease must be measurable by RECIST criteria.

• At least 6 weeks must have elapsed from previous radiation therapy. Patient must have recovered from the acute toxic effects of treatment prior to study enrollment.

• Adequate organ function, as follows:

• Adequate bone marrow reserve: absolute neutrophil count (ANC) ≥ 1.5 X 109/L, platelets ≥ 100 X 109/L, and hemoglobin ≥ 9 g/dL.

• Hepatic: total bilirubin within normal limits (≤ 1.0 mg/dL); alkaline phosphatase (AP), aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 1.5 X ULN (upper limit of normal)

• Renal: Serum creatinine ≤ 1.3 mg/dL. Patients with serum creatinine > 1.3 mg/dL may be eligible if creatinine clearance (CrCl) ≥ 45 mL/min based on the standard Cockroft and Gault formula.

• Patients of childbearing potential must have a negative serum pregnancy test within 14 days of treatment. Patients must agree to use a reliable method of birth control during and for 3 months following the last dose of study drug.

• Patients must sign an informed consent document.

Exclusion Criteria:

• Previous exposure to temsirolimus or other mTOR inhibitors

• More than 2 prior cytotoxic regimens in the recurrent/metastatic disease setting

• History of any brain metastases

• Patients who require concomitant medications that are metabolized by hepatic CYP3A4, due to potential drug-drug interaction with temsirolimus

• Patients with known active interstitial pneumonitis

• Active infection or serious underlying medical condition that would impair the patient's ability to receive protocol treatment.

• Women who are pregnant or lactating

• Other active malignancy, other than indolent malignancies which the investigator determines are unlikely to interfere with treatment and safety analysis

• Diagnosis of Nasopharyngeal cancer is excluded.

• Patients with multifocal peripheral sensory alterations or paresthesias (including tingling) interfering with function, per patient report (example: activities of daily living)

• Therapeutic anticoagulation with Coumadin (warfarin)

• Hypertriglyceridemia ≥ grade 2 (CTCAE version 3.0).

• Impaired lung function: O2 saturation 88% or less at rest on room air by Pulse Oximetry. If O2 saturation is ≤ 88% at rest, further pulmonary function tests (PFTs) should be ordered to confirm normal pulmonary function and eligibility.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan Kettering Cancer Center at Basking Ridge	Basking Ridge	New Jersey	United States	07939
2	Memorial Sloan Kettering Cancer Center @ Suffolk	Commack	New York	United States	11725
3	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
4	Memorial Sloan Kettering at Mercy Medical Center	Rockville Centre	New York	United States
5	Memorial Sloan Kettering Cancer Center at Phelps Memorial Hospital Center	Sleepy Hollow	New York	United States	10591

Sponsors and Collaborators

• Memorial Sloan Kettering Cancer Center
• NATL COMP CA NETWORK
• Pfizer

Investigators

• Principal Investigator: David Pfister, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 22, 2015

More Information

Additional Information:

• Memorial Sloan Kettering Cancer Center

Publications

None provided.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT01016769
• Other Study ID Numbers: 09-131
• First Posted: Nov 19, 2009
• Last Update Posted: Jun 26, 2019
• Last Verified: Jun 1, 2018

• Keywords provided by Memorial Sloan Kettering Cancer Center: Paclitaxel; Carboplatin; Temsirolimus; Head and Neck; recurrent and/or metastatic; 09-131
• Additional relevant MeSH terms: Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Sirolimus; Paclitaxel; Carboplatin

Study Results

Participant Flow

Arm/Group Title	Phase 1, Dose Level 1	Phase 1, Dose Level 2	Phase 1, Dose Level 3	Phase 2, Dose Level 3
Arm/Group Description	Temsirolimus 15mg, Paclitaxel 80mg/m2, Carboplatin AUC 5	Temsirolimus 20mg, Paclitaxel 80mg/m2, Carboplatin AUC	Temsirolimus 25mg, Paclitaxel 80mg/m2, Carboplatin AUC 1.5	Temsirolimus 25mg, Paclitaxel 80mg/m2, Carboplatin AUC 1.5
Period Title: Overall Study
STARTED	4	7	7	30
COMPLETED	3	6	6	30
NOT COMPLETED	1	1	1	0

Baseline Characteristics

Arm/Group Title	Phase 1, Dose Level 1	Phase 1, Dose Level 2	Phase 1, Dose Level 3	Phase 2, Dose Level 3	Total
Arm/Group Description	Temsirolimus 15mg, Paclitaxel 80mg/m2, Carboplatin AUC 5	Temsirolimus 20mg, Paclitaxel 80mg/m2, Carboplatin AUC	Temsirolimus 25mg, Paclitaxel 80mg/m2, Carboplatin AUC 1.5	Temsirolimus 25mg, Paclitaxel 80mg/m2, Carboplatin AUC 1.5	Total of all reporting groups
Overall Participants	4	7	7	30	48
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	3 75%	5 71.4%	6 85.7%	20 66.7%	34 70.8%
>=65 years	1 25%	2 28.6%	1 14.3%	10 33.3%	14 29.2%
Sex: Female, Male (Count of Participants)
Female	0 0%	3 42.9%	1 14.3%	8 26.7%	12 25%
Male	4 100%	4 57.1%	6 85.7%	22 73.3%	36 75%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	1 14.3%	1 3.3%	2 4.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	2 28.6%	0 0%	3 10%	5 10.4%
White	4 100%	5 71.4%	6 85.7%	26 86.7%	41 85.4%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	4 100%	7 100%	7 100%	30 100%	48 100%

Outcome Measures

1. Primary Outcome

Title	Phase II Recommended Dose for the Combination of Temsirolimus + Weekly Paclitaxel + Carboplatin.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

The phase II recommended dose of Temsirolimus was established at dose level three (Carboplatin AUC 1.5, Taxol 80 mg/m2, Temsirolimus 25 mg). 6 participants treated on Phase I, dose level 3 and 30 participants treated on the Phase II portion were combined for analysis.

Arm/Group Title	Temsirolimus + Weekly Paclitaxel + Carboplatin
Arm/Group Description	In Part 2 (Phase II) of the study, the primary endpoint is to determine the objective response rate (CR or PR) after two cycles (approximately 6 weeks) of treatment with the combination of temsirolimus + weekly paclitaxel + carboplatin as palliative therapy for recurrent or metastatic HNSCC. A two-stage design will be employed.
Measure Participants	36
Number [mg]	25

2. Primary Outcome

Title	To Determine the Objective Response Rate (CR or PR) After Two Cycles of Treatment With the Combination of Temsirolimus + Weekly Paclitaxel + Carboplatin as Palliative Therapy for Recurrent or Metastatic HNSCC
Description	Evaluation of target lesions: Complete Response - disappearance of all target lesions Partial Response - at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter Progressive Disease - at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started, or the appearance of one of more new lesions Stable Disease - neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since the treatment started
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

The phase II recommended dose of Temsirolimus was established at dose level three (Carboplatin AUC 1.5, Taxol 80 mg/m2, Temsirolimus 25 mg). 6 participants treated on Phase I, dose level 3 and 30 participants treated on the Phase II portion were combined for analysis.

Arm/Group Title	Temsirolimus + Weekly Paclitaxel + Carboplatin
Arm/Group Description	In Part 2 (Phase II) of the study, the primary endpoint is to determine the objective response rate (CR or PR) after two cycles (approximately 6 weeks) of treatment with the combination of temsirolimus + weekly paclitaxel + carboplatin as palliative therapy for recurrent or metastatic HNSCC. A two-stage design will be employed.
Measure Participants	36
Partial Response	15 375%
Stable Disease	19 475%
Not Evaluable	2 50%

3. Secondary Outcome

Title	Number of Participants Who Experienced Adverse Events
Description	Safety will be assessed in terms of AEs according to CTCAE version 3.0
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Temsirolimus + Weekly Paclitaxel + Carboplatin
Arm/Group Description	In Part 1 (Phase I) of the study, the primary endpoint is to establish the phase II recommended dose for the combination of temsirolimus + weekly paclitaxel + carboplatinPart 1 (Phase I) features a standard 3 + 3 phase I dose escalation design. Up to 3 dose levels are planned in the Phase I portion of the study. In Part 2 (Phase II) of the study, the primary endpoint is to determine the objective response rate (CR or PR) after two cycles (approximately 6 weeks) of treatment with the combination of temsirolimus + weekly paclitaxel + carboplatin as palliative therapy for recurrent or metastatic HNSCC. A two-stage design will be employed.
Measure Participants	48
Count of Participants [Participants]	48 1200%

4. Secondary Outcome

Title	Median Overall Survival
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

The phase II recommended dose of Temsirolimus was established at dose level three (Carboplatin AUC 1.5, Taxol 80 mg/m2, Temsirolimus 25 mg). 7 participants treated on Phase I, dose level 3 and 30 participants treated on the Phase II portion were combined for analysis.

Arm/Group Title	Temsirolimus + Weekly Paclitaxel + Carboplatin
Arm/Group Description	Part 2 (Phase II) of the study, the primary endpoint is to determine the objective response rate (CR or PR) after two cycles (approximately 6 weeks) of treatment with the combination of temsirolimus + weekly paclitaxel + carboplatin as palliative therapy for recurrent or metastatic HNSCC. A two-stage design will be employed.
Measure Participants	37
Median (95% Confidence Interval) [months]	5.9

5. Secondary Outcome

Title	Number of Participants With Potential Molecular Markers of Resistance to mTOR Inhibition
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Temsirolimus + Weekly Paclitaxel + Carboplatin
Arm/Group Description	Part 2 (Phase II) of the study, the primary endpoint is to determine the objective response rate (CR or PR) after two cycles (approximately 6 weeks) of treatment with the combination of temsirolimus + weekly paclitaxel + carboplatin as palliative therapy for recurrent or metastatic HNSCC. A two-stage design will be employed.
Measure Participants	21
PIK3CA Mutation	4 100%
AKT3 S472F Mutation	1 25%
PTEN R130Q Mutation	1 25%
TSC2 Mutation	2 50%
TSC1 Mutation	2 50%

Adverse Events

Time Frame	2 years
Arm/Group Title	Phase 1, Dose Level 1		Phase 1, Dose Level 2		Phase 1, Dose Level 3		Phase 2, Dose Level 3
Arm/Group Description	Temsirolimus 15mg, Paclitaxel 80mg/m2, Carboplatin AUC 5		Temsirolimus 20mg, Paclitaxel 80mg/m2, Carboplatin AUC		Temsirolimus 25mg, Paclitaxel 80mg/m2, Carboplatin AUC 1.5		Temsirolimus 25mg, Paclitaxel 80mg/m2, Carboplatin AUC 1.5
All Cause Mortality
	Phase 1, Dose Level 1		Phase 1, Dose Level 2		Phase 1, Dose Level 3		Phase 2, Dose Level 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/4 (100%)		6/7 (85.7%)		7/7 (100%)		28/30 (93.3%)
Serious Adverse Events
	Phase 1, Dose Level 1		Phase 1, Dose Level 2		Phase 1, Dose Level 3		Phase 2, Dose Level 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/4 (50%)		4/7 (57.1%)		5/7 (71.4%)		21/30 (70%)
Blood and lymphatic system disorders
Febrile neutropenia	0/4 (0%)		1/7 (14.3%)		0/7 (0%)		3/30 (10%)
Cardiac disorders
Atrial fibrillation	1/4 (25%)		0/7 (0%)		0/7 (0%)		0/30 (0%)
Conduct abnorm AV Block- 2nd deg Mobitz type II	0/4 (0%)		0/7 (0%)		0/7 (0%)		1/30 (3.3%)
Supraventricular tachycardia	0/4 (0%)		0/7 (0%)		0/7 (0%)		2/30 (6.7%)
Endocrine disorders
Thyroid function, high	1/4 (25%)		0/7 (0%)		0/7 (0%)		0/30 (0%)
Eye disorders
Ophthalmoplegia/diplopia (double vision)	0/4 (0%)		0/7 (0%)		0/7 (0%)		1/30 (3.3%)
Vitreous hemorrhage	0/4 (0%)		1/7 (14.3%)		0/7 (0%)		0/30 (0%)
Gastrointestinal disorders
Diarrhea	0/4 (0%)		1/7 (14.3%)		0/7 (0%)		2/30 (6.7%)
Dysphagia (Difficulty swallowing)	0/4 (0%)		0/7 (0%)		2/7 (28.6%)		1/30 (3.3%)
Esophagitis	0/4 (0%)		0/7 (0%)		0/7 (0%)		1/30 (3.3%)
Hemorrhage, Rectum	0/4 (0%)		1/7 (14.3%)		0/7 (0%)		0/30 (0%)
Hemorrhage, Upper GI NOS	1/4 (25%)		0/7 (0%)		0/7 (0%)		0/30 (0%)
Nausea	0/4 (0%)		1/7 (14.3%)		1/7 (14.3%)		1/30 (3.3%)
Pain - Abdomen NOS	0/4 (0%)		1/7 (14.3%)		0/7 (0%)		1/30 (3.3%)
Pain - Oral cavity	0/4 (0%)		1/7 (14.3%)		0/7 (0%)		0/30 (0%)
Stricture/stenosis, Esophagus	0/4 (0%)		0/7 (0%)		0/7 (0%)		1/30 (3.3%)
Vomiting	0/4 (0%)		1/7 (14.3%)		2/7 (28.6%)		1/30 (3.3%)
General disorders
Death not assoc w CTCAE term- Sudden death	0/4 (0%)		0/7 (0%)		1/7 (14.3%)		1/30 (3.3%)
Edema: head and neck	0/4 (0%)		0/7 (0%)		1/7 (14.3%)		1/30 (3.3%)
Fatigue (asthenia, lethargy, malaise)	0/4 (0%)		0/7 (0%)		0/7 (0%)		3/30 (10%)
Fever (in the absence of neutropenia)	0/4 (0%)		0/7 (0%)		0/7 (0%)		4/30 (13.3%)
Pain - Face	0/4 (0%)		0/7 (0%)		0/7 (0%)		1/30 (3.3%)
Infections and infestations
Inf norm ANC/gr1/2 neut-Pneumonia(lung)	0/4 (0%)		1/7 (14.3%)		0/7 (0%)		0/30 (0%)
Inf unknown ANC-Peripheral nerve	0/4 (0%)		1/7 (14.3%)		0/7 (0%)		0/30 (0%)
Inf unknown ANC-Pneumonia(lung)	0/4 (0%)		0/7 (0%)		0/7 (0%)		3/30 (10%)
Infection w/ Gr 3/4 neut, Bone (osteomyelitis)	0/4 (0%)		0/7 (0%)		0/7 (0%)		1/30 (3.3%)
Infection w/ Gr 3/4 neut, Lung (pneumonia)	1/4 (25%)		0/7 (0%)		0/7 (0%)		1/30 (3.3%)
Infection, other	0/4 (0%)		0/7 (0%)		0/7 (0%)		1/30 (3.3%)
Investigations
ALT, SGPT	0/4 (0%)		1/7 (14.3%)		0/7 (0%)		0/30 (0%)
AST, SGOT	0/4 (0%)		1/7 (14.3%)		0/7 (0%)		0/30 (0%)
Creatinine	0/4 (0%)		1/7 (14.3%)		0/7 (0%)		0/30 (0%)
Hemoglobin	1/4 (25%)		1/7 (14.3%)		0/7 (0%)		3/30 (10%)
INR	1/4 (25%)		0/7 (0%)		0/7 (0%)		0/30 (0%)
Leukocytes (total WBC)	0/4 (0%)		1/7 (14.3%)		0/7 (0%)		0/30 (0%)
Lymphopenia	1/4 (25%)		0/7 (0%)		0/7 (0%)		0/30 (0%)
Platelets	0/4 (0%)		1/7 (14.3%)		0/7 (0%)		0/30 (0%)
Metabolism and nutrition disorders
Albumin, low (hypoalbuminemia)	0/4 (0%)		1/7 (14.3%)		0/7 (0%)		0/30 (0%)
Calcium, high (hypercalcemia)	0/4 (0%)		0/7 (0%)		0/7 (0%)		1/30 (3.3%)
Calcium, low (hypocalcemia)	1/4 (25%)		0/7 (0%)		0/7 (0%)		0/30 (0%)
Dehydration	0/4 (0%)		0/7 (0%)		1/7 (14.3%)		1/30 (3.3%)
Phosphate, low (hypophosphatemia)	0/4 (0%)		1/7 (14.3%)		0/7 (0%)		0/30 (0%)
Musculoskeletal and connective tissue disorders
Muscle weakness - Whole body/general	0/4 (0%)		0/7 (0%)		0/7 (0%)		1/30 (3.3%)
Pain - Neck	0/4 (0%)		0/7 (0%)		1/7 (14.3%)		0/30 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pain - Tumor pain	0/4 (0%)		0/7 (0%)		0/7 (0%)		1/30 (3.3%)
Nervous system disorders
Dizziness	0/4 (0%)		0/7 (0%)		0/7 (0%)		1/30 (3.3%)
Syncope (fainting)	0/4 (0%)		0/7 (0%)		0/7 (0%)		1/30 (3.3%)
Psychiatric disorders
Mental status	0/4 (0%)		0/7 (0%)		0/7 (0%)		3/30 (10%)
Respiratory, thoracic and mediastinal disorders
Allerg rhinitis (w sneez, nas stuff, postnas drip)	0/4 (0%)		0/7 (0%)		1/7 (14.3%)		1/30 (3.3%)
Aspiration	0/4 (0%)		0/7 (0%)		1/7 (14.3%)		0/30 (0%)
Bronchospasm, wheezing	0/4 (0%)		0/7 (0%)		1/7 (14.3%)		1/30 (3.3%)
Cough	0/4 (0%)		0/7 (0%)		1/7 (14.3%)		2/30 (6.7%)
Dyspnea (shortness of breath)	0/4 (0%)		0/7 (0%)		2/7 (28.6%)		3/30 (10%)
Fistula, pulm/upp respir - Trachea	1/4 (25%)		0/7 (0%)		0/7 (0%)		0/30 (0%)
Hemorrhage, Bronchopulmonary NOS	1/4 (25%)		0/7 (0%)		0/7 (0%)		0/30 (0%)
Hemorrhage, Nose	0/4 (0%)		0/7 (0%)		0/7 (0%)		1/30 (3.3%)
Pain - Throat/pharynx/larynx	0/4 (0%)		1/7 (14.3%)		0/7 (0%)		0/30 (0%)
Pneumothorax	0/4 (0%)		0/7 (0%)		1/7 (14.3%)		0/30 (0%)
Pulm/upp respiratory - Other (spec)	0/4 (0%)		1/7 (14.3%)		0/7 (0%)		0/30 (0%)
Vascular disorders
Hypertension	0/4 (0%)		0/7 (0%)		1/7 (14.3%)		0/30 (0%)
Hypotension	0/4 (0%)		0/7 (0%)		0/7 (0%)		1/30 (3.3%)
Thrombosis/thrombus/embolism	0/4 (0%)		1/7 (14.3%)		0/7 (0%)		4/30 (13.3%)
Other (Not Including Serious) Adverse Events
	Phase 1, Dose Level 1		Phase 1, Dose Level 2		Phase 1, Dose Level 3		Phase 2, Dose Level 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/4 (100%)		7/7 (100%)		7/7 (100%)		30/30 (100%)
Blood and lymphatic system disorders
Hemoglobin	4/4 (100%)		7/7 (100%)		6/7 (85.7%)		30/30 (100%)	35
Cardiac disorders
Palpitations	0/4 (0%)		0/7 (0%)		1/7 (14.3%)		0/30 (0%)
Vent arrhythmia- Ventricular tachycardia	0/4 (0%)		0/7 (0%)		1/7 (14.3%)		1/30 (3.3%)
Sinus tachycardia	0/4 (0%)		0/7 (0%)		0/7 (0%)		4/30 (13.3%)
Ear and labyrinth disorders
Pain - External ear	0/4 (0%)		0/7 (0%)		1/7 (14.3%)		2/30 (6.7%)
Tinnitus	0/4 (0%)		0/7 (0%)		0/7 (0%)		2/30 (6.7%)
Auditory/Ear, other	0/4 (0%)		0/7 (0%)		0/7 (0%)		2/30 (6.7%)
Endocrine disorders
Thyroid function, low	0/4 (0%)		0/7 (0%)		0/7 (0%)		2/30 (6.7%)
Eye disorders
Vision-blurred vision	1/4 (25%)		0/7 (0%)		1/7 (14.3%)		1/30 (3.3%)
Dry eye syndrome	0/4 (0%)		0/7 (0%)		1/7 (14.3%)		0/30 (0%)
Ocular/Visual - Other (specify)	0/4 (0%)		0/7 (0%)		1/7 (14.3%)		3/30 (10%)
Watery eye (epiphora, tearing)	0/4 (0%)		0/7 (0%)		1/7 (14.3%)		2/30 (6.7%)
Gastrointestinal disorders
Constipation	2/4 (50%)		1/7 (14.3%)		4/7 (57.1%)		15/30 (50%)
Diarrhea	2/4 (50%)		3/7 (42.9%)		2/7 (28.6%)		11/30 (36.7%)
Nausea	1/4 (25%)		1/7 (14.3%)		3/7 (42.9%)		12/30 (40%)
Dysphagia (Difficulty swallowing)	2/4 (50%)		5/7 (71.4%)		5/7 (71.4%)		18/30 (60%)
Mucositis - oral cavity	1/4 (25%)		7/7 (100%)		4/7 (57.1%)		17/30 (56.7%)
Pain - Dental/Teeth/Peridontal	0/4 (0%)		1/7 (14.3%)		0/7 (0%)		1/30 (3.3%)
Pain - oral cavity	0/4 (0%)		1/7 (14.3%)		2/7 (28.6%)		7/30 (23.3%)
Vomiting	0/4 (0%)		2/7 (28.6%)		3/7 (42.9%)		6/30 (20%)
Fistula, GI- Oral cavity	0/4 (0%)		0/7 (0%)		1/7 (14.3%)		0/30 (0%)
Dry mouth/salivary gland (xerostomia)	0/4 (0%)		0/7 (0%)		0/7 (0%)		7/30 (23.3%)
Pain - Abdomen NOS	0/4 (0%)		0/7 (0%)		0/7 (0%)		4/30 (13.3%)
Gastritis (incl bile reflux gastritis)	0/4 (0%)		0/7 (0%)		0/7 (0%)		3/30 (10%)
General disorders
Fatigue (asthenia, lethargy, malaise)	2/4 (50%)		6/7 (85.7%)		6/7 (85.7%)		27/30 (90%)
Pain - Pain NOS	1/4 (25%)		0/7 (0%)		1/7 (14.3%)		10/30 (33.3%)
Edema: head and neck	1/4 (25%)		0/7 (0%)		1/7 (14.3%)		6/30 (20%)
Pain - face	1/4 (25%)		0/7 (0%)		2/7 (28.6%)		1/30 (3.3%)
Fever (in the absence of neutropenia)	1/4 (25%)		0/7 (0%)		2/7 (28.6%)		5/30 (16.7%)
Pain - Chest/thorax NOS	0/4 (0%)		1/7 (14.3%)		0/7 (0%)		1/30 (3.3%)
Edema: limb	0/4 (0%)		0/7 (0%)		2/7 (28.6%)		3/30 (10%)
Hemorrhage/Bleeding, other	0/4 (0%)		0/7 (0%)		0/7 (0%)		3/30 (10%)
Flu-like syndrome	0/4 (0%)		0/7 (0%)		0/7 (0%)		3/30 (10%)
Infections and infestations
Pneumonia/Lung Infection	1/4 (25%)		0/7 (0%)		0/7 (0%)		0/30 (0%)
Infection, other	0/4 (0%)		0/7 (0%)		3/7 (42.9%)		10/30 (33.3%)
Investigations
Leukocytes (total WBC)	4/4 (100%)		5/7 (71.4%)		6/7 (85.7%)		26/30 (86.7%)
Platelets	3/4 (75%)		4/7 (57.1%)		5/7 (71.4%)		23/30 (76.7%)
Cholesterol,high(hypercholestremia)	2/4 (50%)		3/7 (42.9%)		4/7 (57.1%)		23/30 (76.7%)
Lymphopenia	3/4 (75%)		6/7 (85.7%)		4/7 (57.1%)		17/30 (56.7%)
Neutrophils/granulocytes (ANC/AGC)	2/4 (50%)		2/7 (28.6%)		3/7 (42.9%)		13/30 (43.3%)
ALT, SGPT	1/4 (25%)		2/7 (28.6%)		2/7 (28.6%)		16/30 (53.3%)
Alkaline phosphatase	1/4 (25%)		3/7 (42.9%)		3/7 (42.9%)		10/30 (33.3%)
AST, SGOT	1/4 (25%)		5/7 (71.4%)		3/7 (42.9%)		9/30 (30%)
INR	1/4 (25%)		1/7 (14.3%)		3/7 (42.9%)		7/30 (23.3%)
Weight Loss	0/4 (0%)		1/7 (14.3%)		0/7 (0%)		11/30 (36.7%)
Creatinine	0/4 (0%)		1/7 (14.3%)		1/7 (14.3%)		4/30 (13.3%)
PTT	0/4 (0%)		0/7 (0%)		0/7 (0%)		4/30 (13.3%)
Metabolism and nutrition disorders
Albumin, low (hypoalbuminemia)	3/4 (75%)		3/7 (42.9%)		7/7 (100%)		22/30 (73.3%)
Glucose, high (hyperglycemia)	4/4 (100%)		5/7 (71.4%)		7/7 (100%)		25/30 (83.3%)
Trglycrde, high (hypertriglyceridemia)	2/4 (50%)		1/7 (14.3%)		3/7 (42.9%)		13/30 (43.3%)
Anorexia	1/4 (25%)		0/7 (0%)		2/7 (28.6%)		5/30 (16.7%)
Calcium, low (hypocalcemia)	1/4 (25%)		1/7 (14.3%)		0/7 (0%)		3/30 (10%)
Magnesium, low (hypomagnesemia)	1/4 (25%)		2/7 (28.6%)		2/7 (28.6%)		10/30 (33.3%)
Potassium, high (hyperkalemia)	1/4 (25%)		2/7 (28.6%)		0/7 (0%)		1/30 (3.3%)
Sodium, low (hyponatremia)	1/4 (25%)		3/7 (42.9%)		6/7 (85.7%)		11/30 (36.7%)
Hypernatremia	0/4 (0%)		3/7 (42.9%)		0/7 (0%)		6/30 (20%)
Phosphate, low (hypophosphatemia)	0/4 (0%)		2/7 (28.6%)		2/7 (28.6%)		6/30 (20%)
Potassium, low (hypokalemia)	0/4 (0%)		2/7 (28.6%)		3/7 (42.9%)		12/30 (40%)
Glucose, low (hypoglycemia)	0/4 (0%)		1/7 (14.3%)		1/7 (14.3%)		3/30 (10%)
Musculoskeletal and connective tissue disorders
Pain - Extremity-limb	1/4 (25%)		0/7 (0%)		0/7 (0%)		2/30 (6.7%)
Joint Pain	0/4 (0%)		2/7 (28.6%)		1/7 (14.3%)		1/30 (3.3%)
Trismus (dffclty,pain whn opn mouth)	0/4 (0%)		1/7 (14.3%)		4/7 (57.1%)		8/30 (26.7%)
Pain - Muscle	0/4 (0%)		1/7 (14.3%)		1/7 (14.3%)		2/30 (6.7%)
Pain - back	0/4 (0%)		1/7 (14.3%)		2/7 (28.6%)		4/30 (13.3%)
Pain - Neck	0/4 (0%)		0/7 (0%)		4/7 (57.1%)		4/30 (13.3%)
Pain - Chest wall	0/4 (0%)		0/7 (0%)		1/7 (14.3%)		5/30 (16.7%)
Muscle weakness - Extremity-lower	0/4 (0%)		0/7 (0%)		0/7 (0%)		2/30 (6.7%)
Nervous system disorders
Neuropathy: sensory	3/4 (75%)		4/7 (57.1%)		4/7 (57.1%)		19/30 (63.3%)
Dizziness	1/4 (25%)		1/7 (14.3%)		2/7 (28.6%)		7/30 (23.3%)
Pain - Head/headache	1/4 (25%)		1/7 (14.3%)		4/7 (57.1%)		3/30 (10%)
Voice changes/dysarthria	0/4 (0%)		0/7 (0%)		2/7 (28.6%)		3/30 (10%)
Taste alteration (dysgeusia)	0/4 (0%)		0/7 (0%)		0/7 (0%)		5/30 (16.7%)
Neuropathy: motor	0/4 (0%)		0/7 (0%)		0/7 (0%)		2/30 (6.7%)
Psychiatric disorders
Mood alteration - Anxiety	0/4 (0%)		0/7 (0%)		1/7 (14.3%)		4/30 (13.3%)
Insomnia	0/4 (0%)		0/7 (0%)		0/7 (0%)		4/30 (13.3%)
Mood alteration - Depression	0/4 (0%)		0/7 (0%)		0/7 (0%)		2/30 (6.7%)
Renal and urinary disorders
Urinary frequency/urgency	0/4 (0%)		0/7 (0%)		1/7 (14.3%)		3/30 (10%)
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)	1/4 (25%)		1/7 (14.3%)		2/7 (28.6%)		10/30 (33.3%)
Pain - Throat/pharynx/larynx	0/4 (0%)		3/7 (42.9%)		2/7 (28.6%)		6/30 (20%)
Cough	0/4 (0%)		5/7 (71.4%)		4/7 (57.1%)		17/30 (56.7%)
Hemorrhage, Bronchopulmonary NOS	0/4 (0%)		1/7 (14.3%)		1/7 (14.3%)		3/30 (10%)
Aspiration	0/4 (0%)		0/7 (0%)		1/7 (14.3%)		0/30 (0%)
Allerg rhinitis (w sneez, nas stuff, postnas drip)	0/4 (0%)		0/7 (0%)		1/7 (14.3%)		2/30 (6.7%)
Hemorrhage, Nose	0/4 (0%)		0/7 (0%)		1/7 (14.3%)		3/30 (10%)
Skin and subcutaneous tissue disorders
Dry Skin	0/4 (0%)		1/7 (14.3%)		1/7 (14.3%)		4/30 (13.3%)
Hair loss/alopecia (scalp or body)	0/4 (0%)		2/7 (28.6%)		2/7 (28.6%)		9/30 (30%)
Rash/desquamation	0/4 (0%)		0/7 (0%)		2/7 (28.6%)		9/30 (30%)
Rash: erythema multiforme	0/4 (0%)		0/7 (0%)		1/7 (14.3%)		2/30 (6.7%)
Pruritus/itching	0/4 (0%)		0/7 (0%)		1/7 (14.3%)		2/30 (6.7%)
Rash: acne/acneiform	0/4 (0%)		0/7 (0%)		1/7 (14.3%)		6/30 (20%)
Dermatology/Skin, other	0/4 (0%)		0/7 (0%)		0/7 (0%)		2/30 (6.7%)
Sweating (diaphoresis)	0/4 (0%)		0/7 (0%)		0/7 (0%)		2/30 (6.7%)
Vascular disorders
Hypertension	1/4 (25%)		1/7 (14.3%)		2/7 (28.6%)		4/30 (13.3%)
Flushing	0/4 (0%)		0/7 (0%)		0/7 (0%)		2/30 (6.7%)

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.