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Phase II Intergroup Phase II Trial of Induction

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S0220 Phase II Intergroup

Coordinating Group: SWOG

A Phase II Trial of Induction Chemoradiotherapy with Cispatin/Etoposide

Followed by Surgical Resection, Followed by Docetaxel for Non-Small Cell

Lung Cancer Involving the Superior Sulcus (Pancoast Tumors)



Intergroup Participants: Date Activated:

SWOG, ACOSOG, CALGB, ECOG, 7/1/2003

NCCTG, NCIC CTG

Study Coordinators:

M Kraut, J Sonett, C Thomas, V Rusch (ACOSOG),

J Jett (NCCTG), H Gillenwater (ECOG),

A Lyss (CALGB), S Laurie (NCIC CTG)

Statisticians:

J Moon, J Crowley

Data Coordinator:

L Kaye









Schema



R Local or distant

Off protocol treatment

E R progression

G E

I CDDP E

S V

+

T A R R

VP-16

R L E E

A + U Docetaxel

G Surgery G

T XRT A X 3 cycles

I T 2 3

O E No distant mets

N No local

R

progression E

Refuse or G Docetaxel

medically unfit X 3 cycles

for surgery 3



Objectives To investigate in an exploratory manner the asso-

To assess the feasibility of administrating a regi- ciation of p27, TUBB-III and Map4 expression

men of cisplatin and etoposide concurrent with a levels with patient responses and outcomes.

program of fractionated chest radiation followed

Patient Population

by surgical resection and consolidation chemo-

Patients must have histologic or cytologic proof

therapy with docetaxel in patients with Pancoast

of a newly diagnosed non-small cell lung carci-

tumors without mediastinal or supraclavicular noma with involvement of the superior sulcus

nodal involvement. (T3-4, N0-1). Disease must be documented by

To assess overall survival, time to progression, both a chest X-ray and a CT scan. Patients with

response (confirmed plus unconfirmed, complete mediastinal or supraclavicular nodal involvement

plus partial during induction), resectability rates (N2-3), two or more parenchymal lesions, or dis-

and toxicity in this patient population treated with tant metastases (including malignant pleural effu-

this regimen. sions) are ineligible.



OCTOBER 4 - 7, 2007 SOUTHWEST ONCOLOGY GROUP LUNG 8



S0220/II

Mediastinal exploration is required to establish Summary Statement

eligibility. Patients must not have had prior thora- As of June 30, 2007, 45 patients have been regis-

cotomy for purposes other than diagnosis or stag- tered. One patient refused protocol treatment and

ing. Patients must not have had any prior chemo- is not analyzable. Twenty-nine patients have pro-

therapy or radiotherapy for lung cancer. ceeded to the surgery step and 19 patients have

been registered to the consolidation step.

All patients must have adequate hematologic, he-

patic, renal, cardiac, and pulmonary function, and Thirty-nine patients have been evaluated for ad-

they must be a candidate for potential future pul- verse events related to concurrent chemoradio-

monary resection as determined by the attending therapy. There has been one treatment-related

thoracic surgeon. Patients with clinical hearing death due to infection with Grade 3-4 neutro-

loss must be willing to accept the potential for penia. Seven additional patients (18%) have ex-

worsening of symptoms. Patients with sympto- perienced Grade 4 adverse events, primarily he-

matic peripheral neuropathy, pericardial effu- matologic. Eighteen patients have been evaluated

sions, or superior vena cava syndrome are ineli- for surgical adverse events. Six patients (33%)

gible. All patients must have a Zubrod perform- were reported as having Grade 3 adverse events

ance status of 0, 1 or 2; those patients with a per- related to surgery. Fifteen patients have been as-

formance status of 2 must also meet additional sessed for adverse events related to consolidation

requirements regarding liver function and weight chemotherapy. Four patients (27%) have experi-

loss. enced Grade 4 adverse events.

Accrual Goals

This study will accrue 45 eligible patients.





Initial Registrations By 3 Month Intervals



10









8



6 6

5



3 3

2 2 2 2 2 2

1 1

0

JAN APR JUL OCT JAN APR JUL OCT JAN APR JUL OCT JAN APR

MAR JUN SEP DEC MAR JUN SEP DEC MAR JUN SEP DEC MAR JUN

2004 2004 2004 2004 2005 2005 2005 2005 2006 2006 2006 2006 2007 2007

Time of Registration

CDDP, VP-16/RT









OCTOBER 4 - 7, 2007 SOUTHWEST ONCOLOGY GROUP LUNG 9



S0220/II

Registration by Institution

Concurrent Chemoradiotherapy

Registrations ending June 30, 2007

Total Total

Institutions Reg Institutions Reg



NCCTG 8 Colorado, U of 1

NCIC 7 Columbia River CCOP 1

ACOSOG 5 ECOG 1

CALGB 4 Grand Rapids CCOP 1

Cincinnati MC, U of 3 Kansas City CCOP 1

Michigan CRC CCOP 3 Loyola University 1

Montana CCOP 2 New Mexico MBCCOP 1

Puget Sound 2 Southeast CCC CCOP 1

Beaumont CCOP 1 Wichita CCOP 1

City of Hope Med Ctr 1 Total (19 Institutions) 45





Registration, Eligibility, and Evaluability

Concurrent Chemoradiotherapy

Registrations ending June 30, 2007; Data as of July 13, 2007

CDDP, CDDP,

VP-16/RT VP-16/RT



NUMBER REGISTERED 45 RESPONSE ASSESSMENT

ELIG./ PEND. ELIG. 45 Determinable 26

Analyzable, Pend. Elig. 3 Not Determinable 2

Not Analyzable 1 Too Early 5

Not Applicable 11

BASELINE DISEASE STATUS

Measurable 31 ADVERSE EVENT ASSESSMENT

Non Measurable 11 Evaluable 39

Too Early 2 Too Early 5





Patient Characteristics

Concurrent Chemoradiotherapy

Registrations ending June 30, 2007; Data as of July 13, 2007

CDDP, VP-16/RT CDDP, VP-16/RT

(n=44) (n=44)

AGE HISPANIC

Median 59.7 No 41 93%

Minimum 44.0 Unknown 3 7%

Maximum 75.1

RACE

SEX White 40 91%

Males 31 70% Asian 3 7%

Females 13 30% Native American 1 2%









OCTOBER 4 - 7, 2007 SOUTHWEST ONCOLOGY GROUP LUNG 10



S0220/II

Treatment Summary

Concurrent Chemoradiotherapy

Registrations ending June 30, 2007; Data as of July 13, 2007

CDDP,

VP-16/RT



NUMBER ON PROTOCOL TREATMENT 6

NUMBER OFF PROTOCOL TREATMENT 38

REASON OFF TREATMENT

Treatment completed as planned 30

Adverse Events or side effects 2

Refusal unrelated to adverse events 1

Progression/relapse 3

Death 0

Other - not protocol specified 0



Reason under review 2

MAJOR PROTOCOL DEVIATIONS 0





Number of Patients with a Given Type and Grade of Adverse Event

Concurrent Chemoradiotherapy

Adverse Events Unlikely or Not Related to Treatment Excluded

Registrations ending June 30, 2007; Data as of July 13, 2007

CDDP, VP-16/RT CDDP, VP-16/RT

(n=39) (n=39)



Grade Grade

ADVERSE EVENT Unk 0 1 2 3 4 5 ADVERSE EVENT Unk 0 1 2 3 4 5



ALT 0 35 2 2 0 0 0 Insomnia 0 38 0 1 0 0 0

AST 0 36 3 0 0 0 0 Leukocytes 0 18 6 3 9 3 0

Alkaline phosphatase 0 38 1 0 0 0 0 Lung Inf, 3-4 ANC: bronchus 0 38 0 0 1 0 0

Allergic reaction 0 38 0 0 0 1 0 Lung Pain: throat/phar/lar 0 38 0 1 0 0 0

Alopecia 0 29 5 5 0 0 0 Lymphopenia 0 35 0 1 2 1 0

Anorexia 0 33 6 0 0 0 0 Memory impairment 0 38 1 0 0 0 0

Bilirubin 0 38 1 0 0 0 0 Metabolic/Lab-other 0 37 1 0 1 0 0

Burn 0 38 1 0 0 0 0 Mood alteration: agitation 0 38 0 1 0 0 0

Constipation 0 30 8 1 0 0 0 Mood alteration: depression 0 38 0 1 0 0 0

Creatinine 0 37 2 0 0 0 0 Mucositis, clin: esophagus 0 38 0 0 1 0 0

Dehydration 0 33 4 0 1 1 0 Mucositis, clin: oral cavity 0 35 3 1 0 0 0

Diarrhea 0 32 3 3 1 0 0 Mucositis, funct: oral cav. 0 37 1 1 0 0 0

Dizziness 0 37 2 0 0 0 0 Mucositis, funct: pharynx 0 37 1 1 0 0 0

Dry skin 0 38 1 0 0 0 0 Musculo. Pain: joint 0 38 0 1 0 0 0

Dysphagia 0 37 1 1 0 0 0 Musculo. Pain: limb 0 38 1 0 0 0 0

Dyspnea 0 38 1 0 0 0 0 Musculo. Pain: muscle 0 38 0 1 0 0 0

Edema-limb 0 38 1 0 0 0 0 Nail changes 0 38 1 0 0 0 0

Esophagitis 1 30 4 3 1 0 0 Nasal/paranasal reactions 0 38 1 0 0 0 0

Fatigue 0 11 15 11 2 0 0 Nausea 0 11 19 8 1 0 0

Febrile neutropenia 0 37 0 0 1 1 0 Neuropathy-sensory 0 34 4 1 0 0 0

Fever 0 37 2 0 0 0 0 Neutrophils 0 21 0 4 9 5 0

Flushing 0 38 1 0 0 0 0 Pain-other 0 36 2 1 0 0 0

GI Pain: abdomen 0 38 0 1 0 0 0 Platelets 0 27 9 3 0 0 0

GI-other 0 35 3 1 0 0 0 Prolapse stoma, GI 0 31 5 3 0 0 0

GU Inf, Unk ANC: UTI 0 38 0 1 0 0 0 RT Dermatitis: ChemoRT derm. 0 38 1 0 0 0 0

GU Pain: bladder 0 38 1 0 0 0 0 RT Dermatitis: RT dermatitis 0 25 11 3 0 0 0

Gastritis 0 37 2 0 0 0 0 Rigors/chills 0 35 4 0 0 0 0

Hearing (w/o monit. prog.) 0 38 0 1 0 0 0 Supra Arrhyth: NOS 0 38 1 0 0 0 0

Hemoglobin 0 16 15 5 3 0 0 Supra Arrhyth: Sinus Brady. 0 38 1 0 0 0 0

Hiccoughs 0 38 0 1 0 0 0 Sweating 0 38 0 1 0 0 0

Hot flashes 0 38 1 0 0 0 0 Taste alteration 0 27 8 4 0 0 0

Hyperglycemia 0 38 1 0 0 0 0 Thrombosis/embolism 0 38 0 0 0 1 0

Hypoalbuminemia 0 35 2 2 0 0 0 Voice changes 0 37 2 0 0 0 0

Hypocalcemia 0 38 0 1 0 0 0 Vomiting 0 25 7 5 2 0 0

Hypokalemia 0 38 1 0 0 0 0 Weight Loss 0 30 6 3 0 0 0

Hypomagnesemia 0 38 1 0 0 0 0 Weight gain 0 38 1 0 0 0 0

Hyponatremia 0 34 4 0 1 0 0

Hypotension 0 36 2 1 0 0 0 MAXIMUM GRADE

Inf, 3-4 ANC: blood 0 38 0 0 0 0 1 ANY ADVERSE EVENT

Infection-other 0 38 1 0 0 0 0 Number 0 0 9 11 11 7 1









OCTOBER 4 - 7, 2007 SOUTHWEST ONCOLOGY GROUP LUNG 11



S0220/II

Registration, Eligibility, and Evaluability

Surgery

Registrations ending June 30, 2007; Data as of July 13, 2007

Surgery Surgery



NUMBER REGISTERED 29 ADVERSE EVENT ASSESSMENT

ELIG./ PEND. ELIG. 29 Evaluable 18

Analyzable, Pend. Elig. 3 Too Early 11





Patient Characteristics

Surgery

Registrations ending June 30, 2007; Data as of July 13, 2007

Surgery Surgery

(n=29) (n=29)

AGE HISPANIC

Median 61.6 No 27 93%

Minimum 44.6 Unknown 2 7%

Maximum 75.3

RACE

SEX White 26 90%

Males 22 76% Asian 2 7%

Females 7 24% Native American 1 3%





Number of Patients with a Given Type and Grade of Adverse Event

Surgery

Adverse Events Unlikely or Not Related to Treatment Excluded

Registrations ending June 30, 2007; Data as of July 13, 2007

Surgery Surgery

(n=18) (n=18)



Grade Grade

ADVERSE EVENT 0 1 2 3 4 5 ADVERSE EVENT 0 1 2 3 4 5



Creatinine 16 2 0 0 0 0 Lung Pain: chest wall 16 0 1 1 0 0

Fatigue 17 0 1 0 0 0 Musculo. Pain: bone 17 0 1 0 0 0

Fever 14 1 3 0 0 0 Musculo. Pain: limb 17 0 0 1 0 0

Hemoglobin 9 3 3 3 0 0 Neuropathy-sensory 16 0 2 0 0 0

Hyperglycemia 16 2 0 0 0 0 Platelets 15 3 0 0 0 0

Hypocalcemia 17 1 0 0 0 0 Pneumothorax 15 2 1 0 0 0

Hypokalemia 17 1 0 0 0 0 Supra Arrhyth: Atrial Fib. 17 0 1 0 0 0

Hypomagnesemia 17 1 0 0 0 0 Supra Arrhyth: Atrial Flut. 17 0 1 0 0 0

Hypophosphatemia 17 0 1 0 0 0 Supra Arrhyth: NOS 16 1 1 0 0 0

Hypotension 17 0 1 0 0 0 Supra Arrhyth: Sinus Tachy. 17 0 1 0 0 0

Hypoxia 16 0 0 2 0 0 Weight Loss 17 0 1 0 0 0

Leukocytes 17 1 0 0 0 0

Lung Inf, 3-4 ANC: lung 17 0 0 1 0 0 MAXIMUM GRADE ANY ADVERSE EVENT

Lung Inf, Unk ANC: lung 17 0 0 1 0 0 Number 2 3 7 6 0 0





Registration, Eligibility, and Evaluability

Consolidation Chemotherapy

Registrations ending June 30, 2007; Data as of July 13, 2007

Consolidation Consolidation

Chemotherapy Chemotherapy



NUMBER REGISTERED 19 ADVERSE EVENT ASSESSMENT

ELIG./ PEND. ELIG. 19 Evaluable 15

Analyzable, Pend. Elig. 3 Too Early 4









OCTOBER 4 - 7, 2007 SOUTHWEST ONCOLOGY GROUP LUNG 12



S0220/II

Patient Characteristics

Consolidation Chemotherapy

Registrations ending June 30, 2007; Data as of July 13, 2007

Consolidation Consolidation

Chemotherapy Chemotherapy

(n=19) (n=19)

AGE HISPANIC

Median 61.7 No 18 95%

Minimum 44.8 Unknown 1 5%

Maximum 74.8

RACE

SEX White 17 89%

Males 14 74% Asian 1 5%

Females 5 26% Native American 1 5%





Treatment Summary

Consolidation Chemotherapy

Registrations ending June 30, 2007; Data as of July 13, 2007

Consolidation

Chemotherapy



NUMBER ON PROTOCOL TREATMENT 4

NUMBER OFF PROTOCOL TREATMENT 15

REASON OFF TREATMENT

Treatment completed as planned 12

Adverse Events or side effects 1

Refusal unrelated to adverse events 0

Progression/relapse 0

Death 0

Other - not protocol specified 1

Reason under review 1

MAJOR PROTOCOL DEVIATIONS 0









OCTOBER 4 - 7, 2007 SOUTHWEST ONCOLOGY GROUP LUNG 13



S0220/II

Number of Patients with a Given Type and Grade of Adverse Event

Consolidation Chemotherapy

Adverse Events Unlikely or Not Related to Treatment Excluded

Registrations ending June 30, 2007; Data as of July 13, 2007

Consolidation Consolidation

Chemotherapy Chemotherapy

(n=15) (n=15)



Grade Grade

ADVERSE EVENT 0 1 2 3 4 5 ADVERSE EVENT 0 1 2 3 4 5



Alopecia 13 0 2 0 0 0 Lymphopenia 13 0 1 1 0 0

Constipation 13 2 0 0 0 0 Mood alteration: depression 14 1 0 0 0 0

Cough 13 1 1 0 0 0 Mucositis, funct: oral cav. 14 0 1 0 0 0

Dehydration 13 1 0 1 0 0 Mucositis, funct: pharynx 14 0 1 0 0 0

Diarrhea 11 2 2 0 0 0 Musculo. Pain: muscle 13 0 2 0 0 0

Dry skin 14 1 0 0 0 0 Nail changes 14 1 0 0 0 0

Dysphagia 14 1 0 0 0 0 Nausea 12 1 1 1 0 0

Dyspnea 13 0 0 2 0 0 Neuropathy-motor 14 1 0 0 0 0

Edema-head and neck 14 1 0 0 0 0 Neuropathy-sensory 10 4 1 0 0 0

Edema-limb 14 1 0 0 0 0 Neutrophils 9 0 0 3 3 0

Fatigue 6 4 4 1 0 0 Pain-other 14 0 0 1 0 0

Fever 13 0 2 0 0 0 Platelets 14 1 0 0 0 0

GI Pain: abdomen 14 0 1 0 0 0 Pleural effusion 13 0 2 0 0 0

GI-other 14 0 1 0 0 0 Pneumonitis 14 1 0 0 0 0

Gastritis 14 1 0 0 0 0 Prolapse stoma, GI 14 0 1 0 0 0

Hand-foot 13 0 2 0 0 0 Pruritus 14 0 1 0 0 0

Hemoglobin 6 5 4 0 0 0 Psychosis 14 0 1 0 0 0

Hyperglycemia 14 0 0 1 0 0 RT Dermatitis: RT dermatitis 14 1 0 0 0 0

Hypoalbuminemia 13 2 0 0 0 0 Rhinitis 14 0 1 0 0 0

Hypocalcemia 14 1 0 0 0 0 Supra Arrhyth: Sinus Tachy. 14 1 0 0 0 0

Hypokalemia 14 1 0 0 0 0 Taste alteration 13 1 1 0 0 0

Hypotension 14 1 0 0 0 0 Vomiting 13 0 1 1 0 0

Hypoxia 14 0 0 1 0 0 Watery eye 14 1 0 0 0 0

Leukocytes 8 1 2 3 1 0 Weight Loss 10 3 1 1 0 0

Lung Hemorrhage: resp. tract 14 0 1 0 0 0

Lung Inf, 3-4 ANC: lung 14 0 0 1 0 0 MAXIMUM GRADE ANY ADVERSE EVENT

Lung Inf, 3-4 ANC: sinus 14 0 1 0 0 0 Number 1 2 2 6 4 0

Lung Pain: chest wall 14 0 1 0 0 0









OCTOBER 4 - 7, 2007 SOUTHWEST ONCOLOGY GROUP LUNG 14



S0220/II



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