Erlotinib in Combination With Docetaxel in Advanced Hepatocellular and Biliary Tract Carcinomas

• Sponsor: Gabi Chiorean, MD (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00532441
• Collaborator: Sanofi (Industry), OSI Pharmaceuticals (Industry)
• Enrollment: 25
• Locations: 12
• Arms: 2
• Duration (Months): 35
• Patients Per Site: 2.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

An unmet medical need exists for the successful therapy of patients with advanced hepatocellular and biliary tract malignances, with few and short lived disease responses to chemotherapy for both advanced stage hepatic and biliary carcinomas. Pre-clinical data shows cooperative antitumor activity between an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor and taxanes. The efficacy of erlotinib in combination with docetaxel will be assessed in this trial.

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma	Drug: Erlotinib; Drug: Docetaxel	Phase 2

Detailed Description

Outline: This is a multi-center study.

Patients who meet eligibility criteria will receive treatment as follows until disease progression or excessive toxicities:

• Erlotinib 150 mg p.o. daily on days 2-7, 9-14, 16-28

• Docetaxel 30 mg/m2 IV over 30 min weekly x 3 weeks on days 1, 8, 15

Treatment cycle = 28 days

Performance Status: Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2

Life expectancy: At least 12 weeks

Hematopoietic:

• Absolute neutrophil count (ANC) > 1000 mm3

• Platelet count > 75,000 mm3

• Hemoglobin > 8 g/dL

Hepatic:

• Bilirubin < 2.0 x upper limit of normal (ULN)

• Transaminases (AST, ALT) < 5.0 x ULN if alkaline phosphatase is < 2.5 x ULN, or alkaline phosphatase < 5 x ULN if transaminases are < 1.5 x ULN.

• If not on anticoagulation: PT < 4 seconds above ULN; INR < 1.5; PTT < 1.3 x ULN.

• If on therapeutic anticoagulation, patients may have an INR > 1.5 and PTT within therapeutic range; INR will be monitored weekly until stable.

• Serum Albumin > 3.0

Renal:

• Creatinine clearance of > 60 ml/ min (by Cockcroft-Gault)

Pulmonary:

• Not specified

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Erlotinib in Combination With Docetaxel in Advanced Hepatocellular and Biliary Tract Carcinomas: Hoosier Oncology Group GI06-101
• Study Start Date: Sep 1, 2007
• Actual Primary Completion Date: Aug 1, 2010
• Actual Study Completion Date: Aug 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Erlotinib and Docetaxel: Biliary Erlotinib 150 mg p.o. daily, days 2-7, 9-14, 16-28 Docetaxel 30 mg/m2 IV over 30 min weekly x 3 weeks on days 1, 8 and 15	Drug: Erlotinib; Erlotinib 150 mg p.o. daily, days 2-7, 9-14, 16-28; Drug: Docetaxel; Docetaxel 30 mg/m2 IV over 30 min weekly x 3 weeks on days 1, 8 and 15
Experimental: Erlotinib and Docetaxel: Hepatocellular Erlotinib 150 mg p.o. daily, days 2-7, 9-14, 16-28 Docetaxel 30 mg/m2 IV over 30 min weekly x 3 weeks on days 1, 8 and 15	Drug: Erlotinib; Erlotinib 150 mg p.o. daily, days 2-7, 9-14, 16-28; Drug: Docetaxel; Docetaxel 30 mg/m2 IV over 30 min weekly x 3 weeks on days 1, 8 and 15

Outcome Measures

Primary Outcome Measures

1. 16 Weeks Progression-free Survival [Start of treatment until disease progression per RECIST criteria up to 16 weeks]

   To determine the rate of progression-free survival (PFS) at 16 weeks for the combination therapy of erlotinib and docetaxel for subjects in the Biliary stratum, per RECIST criteria. Progressive disease is defined as at least a 20% increase in the sum of the longest diameter of target lesions taking as reference the smallest sum recorded since the treatment started or the appearance of one or more new lesions.

Secondary Outcome Measures

1. Response Rate [18 months]

   Determine the Response Rate Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0)

2. Overall Survival [18 Months]

   Determine Overall Survival

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histological or cytological proof of hepatocellular or biliary tract carcinomas, not amenable to curative resection or transplantation.

• Prior cancer treatment completed at least 30 days prior to being registered for protocol therapy and recovered from the acute toxicity effects of the regimen.

• Patients may have had radiofrequency ablation, cryosurgery or embolization, but must have documented progressive disease with the involved lesion, or at least one previously untreated lesion.

• Patients may have had ≤ 2 prior chemotherapy regimens.

• Prior radiation therapy allowed to < 25% of the bone marrow at least 30 days prior to being registered for protocol therapy.

• Patients with biliary obstruction must have percutaneous transhepatic drainage or endoscopic stent placement prior to starting study treatment.

• Patients with a history of malignancy are eligible provided they have been curatively treated and demonstrate no evidence for recurrence of that cancer.

• Peripheral neuropathy ≤ grade 1.

• Patients must agree to abstain from frozen or fresh grapefruit or grapefruit juice for 5 days prior to, and during treatment.

• Patients must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) while on treatment and for a 12 week period thereafter.

• Females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for protocol therapy.

• Written informed consent and HIPAA authorization for release of personal health information.

• Age ≥ 18 years at time of consent.

Exclusion Criteria:

• No previous treatment with EGFR inhibitors.

• No treatment with any investigational agent within 30 days prior to being registered for protocol therapy.

• No symptomatic brain metastasis. A subject with prior brain metastasis may be considered if they have completed their treatment for brain metastasis, no longer require corticosteroids, and are asymptomatic.

• No Child-Pugh B or C liver cirrhosis.

• No active corneal erosions or history of abnormal corneal sensitivity test.

• No history of aneurysm or arteriovenous malformation.

• No hemorrhage/bleeding event > CTCAE Grade 3 within 30 days prior to begin registered for protocol therapy.

• No clinically significant infections as judged by the treating investigator.

• No condition that impairs patient's ability to swallow whole pills.

• No history of hypersensitivity to docetaxel or other drugs formulated with polysorbate

• Females must not be breastfeeding.

• Patients who cannot avoid the following medications will be ineligible for the trial: midazolam, anti-mycotic agents (ketoconazole and related compounds), macrolide antibiotics (erythromycin and related compounds), nifedipine, phenobarbital, phenytoin, carbamazepine, and rifampin (induction) and anti-retrovirals (including ritonavir, saquinavir).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Helen F. Graham Cancer Center	Newark	Delaware	United States	19713
2	Northwestern University Feinberg School of Medicine	Chicago	Illinois	United States	60611
3	Rush-Presbyterian St. Luke's Medical Center	Chicago	Illinois	United States	60612
4	Cancer Care Center of Southern Indiana	Bloomington	Indiana	United States	47403
5	Fort Wayne Oncology & Hematology, Inc	Fort Wayne	Indiana	United States	46815
6	IN Onc/Hem Associates	Indianapolis	Indiana	United States	46202
7	Indiana University Cancer Center	Indianapolis	Indiana	United States	46202
8	Quality Cancer Center (MCGOP)	Indianapolis	Indiana	United States	46202
9	Medical Consultants, P.C.	Muncie	Indiana	United States	47303
10	Northern Indiana Cancer Research Consortium	South Bend	Indiana	United States	46601
11	Siteman Cancer Center	St. Louis	Missouri	United States	63110
12	Methodist Cancer Center	Omaha	Nebraska	United States	68114

Sponsors and Collaborators

• Gabi Chiorean, MD
• Sanofi
• OSI Pharmaceuticals

Investigators

• Study Chair: Elena Gabriela Chiorean, M.D., Hoosier Oncology Group, LLC

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Hoosier Oncology Group Home Page

Publications

None provided.

• Responsible Party: Gabi Chiorean, MD, Principal Investigator, Hoosier Cancer Research Network
• ClinicalTrials.gov Identifier: NCT00532441
• Other Study ID Numbers: GI06-101
• First Posted: Sep 20, 2007
• Last Update Posted: Feb 12, 2016
• Last Verified: Jan 1, 2016

• Additional relevant MeSH terms: Carcinoma; Docetaxel; Erlotinib Hydrochloride

Study Results

Participant Flow

Arm/Group Title	Hepatocellular	Biliary
Arm/Group Description	erlotinib and docetaxel	erlotinib and docetaxel
Period Title: Overall Study
STARTED	14	11
COMPLETED	13	11
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Erlotinib and Docetaxel
Arm/Group Description	Erlotinib 150 mg p.o. daily, days 2-7, 9-14, 16-28 Docetaxel 30 mg/m2 IV over 30 min weekly x 3 weeks on days 1, 8 and 15 Erlotinib: Erlotinib 150 mg p.o. daily, days 2-7, 9-14, 16-28 Docetaxel: Docetaxel 30 mg/m2 IV over 30 min weekly x 3 weeks on days 1, 8 and 15
Overall Participants	25
Age, Customized (years) [Median (Full Range) ]
Age	63.5
Sex: Female, Male (Count of Participants)
Female	10 40%
Male	15 60%
Region of Enrollment (participants) [Number]
United States	25 100%
ECOG Performance Status (participants) [Number]
ECOG 0	11 44%
ECOG 1	12 48%
ECOG 2	2 8%
Cancer Type or Histologic Subtype (participants) [Number]
Biliary	11 44%
Hepatocellular	14 56%
Biliary Cancer Site (participants) [Number]
Cholangiocarcoma	6 24%
Gallbladder	5 20%
N/A	14 56%
Disease Status (participants) [Number]
Locally Advanced: Biliary	0 0%
Locally Advanced: Hepatocellular	4 16%
Metastatic: Biliary	11 44%
Metastatic: Hepatocellular	10 40%
Previous Treatment (participants) [Number]
Biliary: Chemotherapy	7 28%
Biliary: Targeted therapy (sorafenib)	0 0%
Biliary: Radiotherapy	3 12%
Biliary: Y90 Radioembolization	0 0%
Biliary: Surgery	2 8%
Hepatocellular: Chemotherapy	3 12%
Hepatocellular:Targeted therapy (sorafenib)	7 28%
Hepatocellular:Radiotherapy	2 8%
Hepatocellular: Y90 Radioembolization	2 8%
Hepatocellular:Surgery	3 12%
Number of Prior Systemic Therapies (participants) [Number]
Biliary: 1 Prior therapy	6 24%
Biliary: >1 Prior Therapy	1 4%
Hepatocellular: 1 Prior Therapy	6 24%
Hepatocellular: >1 Prior Therapy	2 8%

Outcome Measures

1. Primary Outcome

Title	16 Weeks Progression-free Survival
Description	To determine the rate of progression-free survival (PFS) at 16 weeks for the combination therapy of erlotinib and docetaxel for subjects in the Biliary stratum, per RECIST criteria. Progressive disease is defined as at least a 20% increase in the sum of the longest diameter of target lesions taking as reference the smallest sum recorded since the treatment started or the appearance of one or more new lesions.
Time Frame	Start of treatment until disease progression per RECIST criteria up to 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Biliary	Hepatocellular
Arm/Group Description	Erlotinib 150 mg p.o. daily, days 2-7, 9-14, 16-28 Docetaxel 30 mg/m2 IV over 30 min weekly x 3 weeks on days 1, 8 and 15 Erlotinib: Erlotinib 150 mg p.o. daily, days 2-7, 9-14, 16-28 Docetaxel: Docetaxel 30 mg/m2 IV over 30 min weekly x 3 weeks on days 1, 8 and 15	Erlotinib 150 mg p.o. daily, days 2-7, 9-14, 16-28 Docetaxel 30 mg/m2 IV over 30 min weekly x 3 weeks on days 1, 8 and 15 Erlotinib: Erlotinib 150 mg p.o. daily, days 2-7, 9-14, 16-28 Docetaxel: Docetaxel 30 mg/m2 IV over 30 min weekly x 3 weeks on days 1, 8 and 15
Measure Participants	11	14
Median (95% Confidence Interval) [months]	4.7	3.5

2. Secondary Outcome

Title	Response Rate
Description	Determine the Response Rate Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0)
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Erlotinib and Docetaxel: Biliary	Erlotinib and Docetaxel: Hepatocellular
Arm/Group Description	Erlotinib 150 mg p.o. daily, days 2-7, 9-14, 16-28 Docetaxel 30 mg/m2 IV over 30 min weekly x 3 weeks on days 1, 8 and 15 Erlotinib: Erlotinib 150 mg p.o. daily, days 2-7, 9-14, 16-28 Docetaxel: Docetaxel 30 mg/m2 IV over 30 min weekly x 3 weeks on days 1, 8 and 15	Erlotinib 150 mg p.o. daily, days 2-7, 9-14, 16-28 Docetaxel 30 mg/m2 IV over 30 min weekly x 3 weeks on days 1, 8 and 15 Erlotinib: Erlotinib 150 mg p.o. daily, days 2-7, 9-14, 16-28 Docetaxel: Docetaxel 30 mg/m2 IV over 30 min weekly x 3 weeks on days 1, 8 and 15
Measure Participants	11	13
Complete Response or Partial Response	0 0%	0 NaN
Stable Disease	7 28%	6 NaN
Progressive Disease	4 16%	7 NaN

3. Secondary Outcome

Title	Overall Survival
Description	Determine Overall Survival
Time Frame	18 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hepatocellular	Biliary
Arm/Group Description	erlotinib and docetaxel	erlotinib and docetaxel
Measure Participants	13	11
Median (95% Confidence Interval) [months]	6.7	5.7

Adverse Events

Time Frame	16 weeks
Arm/Group Title	Erlotinib and Docetaxel
Arm/Group Description	Erlotinib 150 mg p.o. daily, days 2-7, 9-14, 16-28 Docetaxel 30 mg/m2 IV over 30 min weekly x 3 weeks on days 1, 8 and 15 Erlotinib: Erlotinib 150 mg p.o. daily, days 2-7, 9-14, 16-28 Docetaxel: Docetaxel 30 mg/m2 IV over 30 min weekly x 3 weeks on days 1, 8 and 15
All Cause Mortality
	Erlotinib and Docetaxel
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Erlotinib and Docetaxel
	Affected / at Risk (%)	# Events
Total	9/25 (36%)
Gastrointestinal disorders
ESOPHAGITIS	1/25 (4%)	2
GASTROINTESTINAL - OTHER (SPECIFY, __)	1/25 (4%)	1
HEMORRHAGE, GI / LOWER GI NOS	1/25 (4%)	1
PAIN / ABDOMEN NOS	1/25 (4%)	1
General disorders
DEATH NOT ASSOCIATED WITH CTCAE TERM / DEATH NOS	1/25 (4%)	1
Hepatobiliary disorders
LIVER DYSFUNCTION/FAILURE (CLINICAL)	1/25 (4%)	1
Infections and infestations
INFECTION - OTHER (SPECIFY, __)	1/25 (4%)	1
INFECTION WITH NORMAL ANC OR GRADE 1 OR 2 NEUTROPHILS / CATHETER-RELATED	1/25 (4%)	1
INFECTION WITH NORMAL ANC OR GRADE 1 OR 2 NEUTROPHILS / LUNG (PNEUMONIA)	1/25 (4%)	1
Investigations
BILIRUBIN (HYPERBILIRUBINEMIA)	1/25 (4%)	1
CALCIUM, SERUM-HIGH (HYPERCALCEMIA)	1/25 (4%)	1
Respiratory, thoracic and mediastinal disorders
DYSPNEA (SHORTNESS OF BREATH)	1/25 (4%)	1
PLEURAL EFFUSION (NON-MALIGNANT)	1/25 (4%)	1
Other (Not Including Serious) Adverse Events
	Erlotinib and Docetaxel
	Affected / at Risk (%)	# Events
Total	25/25 (100%)
Blood and lymphatic system disorders
EDEMA: LIMB	8/25 (32%)	10
HEMOGLOBIN	6/25 (24%)	10
HEMOLYSIS (E.G., IMMUNE HEMOLYTIC ANEMIA, DRUG-RELATED HEMOLYSIS)	1/25 (4%)	9
LEUKOCYTES (TOTAL WBC)	4/25 (16%)	4
LYMPHOPENIA	3/25 (12%)	3
NEUTROPHILS/GRANULOCYTES (ANC/AGC)	2/25 (8%)	3
PLATELETS	2/25 (8%)	3
Cardiac disorders
CARDIAC ARRHYTHMIA - OTHER (SPECIFY, __)	1/25 (4%)	1
HYPERTENSION	2/25 (8%)	2
HYPOTENSION	1/25 (4%)	1
SUPRAVENTRICULAR AND NODAL ARRHYTHMIA / ATRIAL FIBRILLATION	1/25 (4%)	1
SUPRAVENTRICULAR AND NODAL ARRHYTHMIA / ATRIAL TACHYCARDIA/PAROXYSMAL ATRIAL TACHYCARDIA	1/25 (4%)	1
Endocrine disorders
HOT FLASHES/FLUSHES	1/25 (4%)	1
Eye disorders
WATERY EYE (EPIPHORA, TEARING)	4/25 (16%)	4
Gastrointestinal disorders
ANOREXIA	11/25 (44%)	21
CONSTIPATION	10/25 (40%)	22
DEHYDRATION	4/25 (16%)	4
DIARRHEA	15/25 (60%)	24
DISTENSION/BLOATING, ABDOMINAL	1/25 (4%)	1
ESOPHAGITIS	1/25 (4%)	1
FLATULENCE	1/25 (4%)	1
GASTROINTESTINAL - OTHER (SPECIFY, __)	3/25 (12%)	3
HEARTBURN/DYSPEPSIA	4/25 (16%)	4
HEMORRHAGE, GI / RECTUM	1/25 (4%)	1
HEMORRHOIDS	2/25 (8%)	3
INCONTINENCE, ANAL	1/25 (4%)	1
MUCOSITIS/STOMATITIS (FUNCTIONAL/SYMPTOMATIC) / ORAL CAVITY	3/25 (12%)	4
NAUSEA	14/25 (56%)	22
PAIN / ABDOMEN NOS	11/25 (44%)	14
PAIN / ESOPHAGUS	1/25 (4%)	1
STRICTURE/STENOSIS (INCLUDING ANASTOMOTIC), GI / DUODENUM	1/25 (4%)	1
TASTE ALTERATION (DYSGEUSIA)	10/25 (40%)	15
VOMITING	9/25 (36%)	11
General disorders
CONSTITUTIONAL SYMPTOMS - OTHER (SPECIFY, __)	1/25 (4%)	1
FATIGUE (ASTHENIA, LETHARGY, MALAISE)	19/25 (76%)	35
FEVER (IN THE ABSENCE OF NEUTROPENIA, WHERE NEUTROPENIA IS DEFINED AS ANC <1.0 X 10E9/L)	6/25 (24%)	9
INSOMNIA	5/25 (20%)	5
PAIN / BACK	3/25 (12%)	5
PAIN / BUTTOCK	1/25 (4%)	1
PAIN / HEAD/HEADACHE	3/25 (12%)	4
PAIN / SINUS	1/25 (4%)	1
PAIN - OTHER (SPECIFY, __)	1/25 (4%)	1
RIGORS/CHILLS	1/25 (4%)	1
SWEATING (DIAPHORESIS)	2/25 (8%)	3
WEIGHT GAIN	1/25 (4%)	2
WEIGHT LOSS	5/25 (20%)	6
Hepatobiliary disorders
PAIN / GALLBLADDER	1/25 (4%)	1
PAIN / LIVER	1/25 (4%)	2
Immune system disorders
ALLERGIC REACTION/HYPERSENSITIVITY (INCLUDING DRUG FEVER)	1/25 (4%)	1
ALLERGIC RHINITIS (INCLUDING SNEEZING, NASAL STUFFINESS, POSTNASAL DRIP)	2/25 (8%)	3
CYTOKINE RELEASE SYNDROME/ACUTE INFUSION REACTION	1/25 (4%)	1
Infections and infestations
INFECTION - OTHER (SPECIFY, __)	2/25 (8%)	2
INFECTION WITH NORMAL ANC OR GRADE 1 OR 2 NEUTROPHILS / LUNG (PNEUMONIA)	1/25 (4%)	1
INFECTION WITH NORMAL ANC OR GRADE 1 OR 2 NEUTROPHILS / UPPER AIRWAY NOS	1/25 (4%)	1
INFECTION WITH NORMAL ANC OR GRADE 1 OR 2 NEUTROPHILS / URINARY TRACT NOS	1/25 (4%)	1
INFECTION WITH UNKNOWN ANC / CONJUNCTIVA	1/25 (4%)	1
Investigations
ALBUMIN, SERUM-LOW (HYPOALBUMINEMIA)	3/25 (12%)	6
ALKALINE PHOSPHATASE	10/25 (40%)	16
ALT, SGPT (SERUM GLUTAMIC PYRUVIC TRANSAMINASE)	8/25 (32%)	12
AST, SGOT(SERUM GLUTAMIC OXALOACETIC TRANSAMINASE)	8/25 (32%)	12
BILIRUBIN (HYPERBILIRUBINEMIA)	5/25 (20%)	6
CALCIUM, SERUM-LOW (HYPOCALCEMIA)	2/25 (8%)	2
CHOLESTEROL, SERUM-HIGH (HYPERCHOLESTREMIA)	1/25 (4%)	1
CREATININE	1/25 (4%)	1
GLUCOSE, SERUM-HIGH (HYPERGLYCEMIA)	7/25 (28%)	13
METABOLIC/LABORATORY - OTHER (SPECIFY, __)	1/25 (4%)	3
POTASSIUM, SERUM-HIGH (HYPERKALEMIA)	2/25 (8%)	4
SODIUM, SERUM-LOW (HYPONATREMIA)	2/25 (8%)	4
Musculoskeletal and connective tissue disorders
ARTHRITIS (NON-SEPTIC)	1/25 (4%)	1
MUSCLE WEAKNESS, GENERALIZED OR SPECIFIC AREA (NOT DUE TO NEUROPATHY) / EXTREMITY-LOWER	1/25 (4%)	1
MUSCLE WEAKNESS, GENERALIZED OR SPECIFIC AREA (NOT DUE TO NEUROPATHY) / WHOLE BODY/GENERALIZED	2/25 (8%)	2
PAIN / BONE	3/25 (12%)	3
PAIN / EXTREMITY-LIMB	4/25 (16%)	5
PAIN / JOINT	2/25 (8%)	2
PAIN / MUSCLE	1/25 (4%)	2
Nervous system disorders
CONFUSION	1/25 (4%)	1
DIZZINESS	6/25 (24%)	11
EXTRAPYRAMIDAL/INVOLUNTARY MOVEMENT/RESTLESSNESS	1/25 (4%)	2
NEUROPATHY: SENSORY	7/25 (28%)	9
Psychiatric disorders
MOOD ALTERATION / ANXIETY	5/25 (20%)	5
MOOD ALTERATION / DEPRESSION	1/25 (4%)	1
Renal and urinary disorders
INCONTINENCE, URINARY	1/25 (4%)	1
RENAL/GENITOURINARY - OTHER (SPECIFY, __)	1/25 (4%)	1
Respiratory, thoracic and mediastinal disorders
COUGH	9/25 (36%)	12
DYSPNEA (SHORTNESS OF BREATH)	7/25 (28%)	11
FISTULA, PULMONARY/UPPER RESPIRATORY / BRONCHUS	1/25 (4%)	1
HEMORRHAGE, PULMONARY/UPPER RESPIRATORY / NOSE	1/25 (4%)	1
PAIN / CHEST WALL	1/25 (4%)	1
PAIN / CHEST/THORAX NOS	1/25 (4%)	1
PULMONARY/UPPER RESPIRATORY - OTHER (SPECIFY, __)	2/25 (8%)	2
Skin and subcutaneous tissue disorders
DERMATOLOGY/SKIN - OTHER (SPECIFY, __)	6/25 (24%)	7
HAIR LOSS/ALOPECIA (SCALP OR BODY)	11/25 (44%)	12
NAIL CHANGES	1/25 (4%)	1
PRURITUS/ITCHING	3/25 (12%)	4
RASH/DESQUAMATION	9/25 (36%)	15
RASH: ACNE/ACNEIFORM	11/25 (44%)	16
RASH: DERMATITIS ASSOCIATED WITH RADIATION / RADIATION	1/25 (4%)	1
RASH: HAND-FOOT SKIN REACTION	2/25 (8%)	3
Surgical and medical procedures
MUCOSITIS/STOMATITIS (CLINICAL EXAM) / ORAL CAVITY	8/25 (32%)	13
Vascular disorders
THROMBOSIS/THROMBUS/EMBOLISM	1/25 (4%)	1

Limitations/Caveats

No statistical correlations with PFS and OS could be performed due to the small number of KRAS mutations.

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.