Appendix 2 contains tabular summaries for those patients who achieved an objective MTT response (by study) and those who achieved Patient Benefit. Also included in this appendix are synopses for six patients. These are included to provide individual examples of the types of patients that were treated in the Phase III studies. For three of the patients, photographs of the patients prior to and after treatment are included.

  1. Outcomes Tables
  2. The following tables include individual outcomes for patients with objective response of the MTT or who achieved Patient Benefit in the blinded phase of studies 414 and 514:

    Table A2-1

    Patients Who Achieved An MTT Response, Study 414 - Blinded Phase

    Table A2-2

    Patients Who Achieved An MTT Response, Study 514 - Blinded Phase

    Table A2-3

    Treatment Goals For Patients Who Achieved An MTT Response, Study 414 - Blinded Phase

    Table A2-4

    Treatment Goals For Patients Who Achieved An MTT Response, Study 514 - Blinded Phase

    Table A2-5

    Patients Who Achieved Patient Benefit, Study 414

    Table A2-6

    Patients Who Achieved Patient Benefit, Study 514

    Table A2-1: Patients Who Achieved an MTT Response, Study 414 Blinded Phase

    Pt.

    No.

    Treatment

    Group

    Response

    Duration of Response (days)

    Time to Response

    Site of 1

    Cancer

    MTT Location

    Baseline

    MTT Vol. (cm3)

    Prior Chemotherapy

    Previous RT for MTT or MTT Field?

    Days

    # of Rxs

    5301

    CDDP/epi gel

    CR

    168+

    21

    2

    Nasal cavity

    Nasopharyngeal

    3.23

    No

    Yes

    1995

    CDDP/epi gel

    CR

    120+

    14

    2

    Nasal cavity

    Facial

    0.500

    Yes (Pt)

    Yes

    5111

    CDDP/epi gel

    CR

    105+

    28

    3

    Unknown

    Facial

    2.00

    No

    Yes

    1998

    CDDP/epi gel

    CR

    103+

    14

    2

    Larynx

    Cervical

    3.00

    Yes (Pt)

    Yes

    4964

    CDDP/epi gel

    CR

    99+

    47

    5

    Oral cavity

    Cervical

    8.75

    Yes (Pt)

    Yes

    2000

    CDDP/epi gel

    CR

    97+

    28

    2

    Oropharynx

    Cervical

    0.625

    No

    Yes

    5036

    CDDP/epi gel

    CR

    95+

    17

    2

    Oral cavity

    Facial

    7.81

    Yes (Pt)

    Yes

    5348

    CDDP/epi gel

    CR

    85+

    21

    3

    Oral cavity

    Cervical

    13.5

    Yes (Pt)

    Yes

    1993

    CDDP/epi gel

    CR

    78+

    35

    5

    Larynx

    Cervical

    2.50

    No

    Yes

    2136

    CDDP/epi gel

    CR

    77+

    7

    1

    Salivary glands

    Cervical

    0.600

    Yes (Pt)

    Yes

    5303

    CDDP/epi gel

    CR

    64+

    14

    2

    Oral cavity

    Facial

    0.900

    Yes (Pt)

    Yes

    5134

    CDDP/epi gel

    CR

    37+

    9

    1

    Larynx

    Cervical

    1.25

    No

    Yes

    5151

    CDDP/epi gel

    CR

    36+

    7

    1

    Oral cavity

    Facial

    17.5

    No

    Yes

    1825

    CDDP/epi gel

    CR

    34a

    20

    2

    Unknown

    Oral

    0.504

    No

    No

    Time to response: Time to beginning of PR or CR

    Duration of response: calculated from the onset of PR or CR until "censored" at the time of relapse, initiation of confounding therapy, or death

    "Pt" indicates platinum-based chemotherapy (cisplatin, carboplatin)

    Plus sign (+) indicates that the tumor was responding at the time of the last evaluation

    a Time to progression: 216+ days

     

    Table A2-1: Patients Who Achieved an MTT Response, Study 414 Blinded Phase (continued)

    Pt.

    No.

    Treatment Group

    Response

    Duration of Response (days)

    Time to Response

    Site of 1 Cancer

    MTT Location

    Baseline

    MTT Vol. (cm3)

    Prior Chemotherapy

    Previous RT for MTT or MTT Field?

    Days

    # of Rxs

    1797

    CDDP/epi gel

    PR

    124+

    21

    2

    Unknown

    Cranial

    6.00

    Yes (Pt)

    Yes

    5372

    CDDP/epi gel

    PR

    119+

    35

    5

    Unknown

    Facial

    18.8

    Yes (Pt)

    Yes

    5133

    CDDP/epi gel

    PR

    99+

    16

    2

    Oropharynx

    Oral

    4.00

    No

    Yes

    5110

    CDDP/epi gel

    PR

    75+

    14

    2

    Oropharynx

    Cervical

    2.00

    Yes (Pt)

    Yes

    1772

    CDDP/epi gel

    PR

    53+

    50

    6

    Oropharynx

    Oral

    11.3

    Yes

    Yes

    2110

    CDDP/epi gel

    PR

    43+

    14

    2

    Oropharynx

    Oral

    7.50

    Yes (Pt)

    Yes

    1992

    CDDP/epi gel

    PR

    35b

    14

    2

    Unknown

    Cervical

    2.00

    Yes (Pt)

    Yes

    Time to response: Time to beginning of PR or CR

    Duration of response: calculated from the onset of PR or CR until "censored" at the time of relapse, initiation of confounding therapy, or death

    "Pt" indicates platinum-based chemotherapy (cisplatin, carboplatin)

    Plus sign (+) indicates that the tumor was responding at the time of the last evaluation

    b Time to progression: 49 days

     

     

    Table A2-2: Patients Who Achieved an MTT Response, Study 514 Blinded Phase

    Pt.

    No.

    Treatment Group

    Response

    Duration of Response (days)

    Time to

    Response

    Site of 1 Cancer

    MTT Location

    Baseline MTT Vol. (cm3)

    Prior Chemotherapy

    Previous RT for MTT or MTT Field?

    Days

    # of Rxs

    2732

    CDDP/epi gel

    CR

    554+

    10

    1

    Unknown

    Oral

    9

    No

    Yes

    2681

    CDDP/epi gel

    CR

    391+

    14

    2

    Oral cavity

    Facial

    12.4

    No

    Yes

    5565

    CDDP/epi gel

    CR

    136+

    60

    6

    Hypopharynx

    Oral

    0.75

    No

    No

    2736

    CDDP/epi gel

    CR

    113+

    97

    6

    Oral cavity

    Oral

    4.0

    Yes (Pt)

    Yes

    2686

    CDDP/epi gel

    CR

    64+

    28

    3

    Nasopharynx

    Oral

    2

    No

    Yes

    2735

    CDDP/epi gel

    CR

    57+

    112

    6

    Oropharynx

    Oral c

    2.92

    No

    Yes

    5854

    CDDP/epi gel

    CR

    55+

    14

    2

    Oral cavity

    Cervicala

    2.52

    No

    No

    5495

    Placebo

    CR

    54+

    56

    5

    Unknown

    Cervical

    0.75

    No

    Yes

    2687

    CDDP/epi gel

    CR

    49+

    105

    6

    Oropharynx

    Oral

    1

    No

    Yes

    2731

    CDDP/epi gel

    CR

    46+

    46

    5

    Unknown

    Facial

    10.9

    No

    Yes

    5496

    CDDP/epi gel

    PR

    93+

    35

    4

    Oral cavity

    Oral

    1.25

    No

    Yes

    2688

    CDDP/epi gel

    PR

    84+

    63

    6

    Oropharynx

    Oral

    1.5

    Yes (Pt)

    Yes

    2753

    CDDP/epi gel

    PR

    64+

    104

    6

    Larynx

    Oral

    15.8

    No

    Yes

    2541

    CDDP/epi gel

    PR

    58+

    162

    1

    Larynx

    Cervicalb

    4.95

    No

    Yes

    5494

    CDDP/epi gel

    PR

    30+

    21

    3

    Oral cavity

    Oral

    3.75

    Yesc

    Yes

    Time to response: Time to beginning of PR or CR

    Duration of response: calculated from the onset of PR or CR until "censored" at the time of relapse, initiation of confounding therapy, or death

    "Pt" indicates platinum-based chemotherapy (cisplatin, carboplatin)

    Plus sign (+) indicates that the tumor was responding at the time of the last evaluation

    aUpper anterior chest wall

    bSupraclavicular

    c "LV," 5-FU

     

     

    Table A2-3: Treatment Goals for Patients Who Achieved an MTT Response, Study 414 Blinded Phase

    Pt.

    No.

    Treatment Group

    Response

    Patient

    Benefit Achieved

    MTT Location

    1 Treatment Goal

    (Patient)

    1 Treatment Goal

    (Investigator)

    Goal

    Outcome

    Goal

    Outcome

    5301

    CDDP/epi gel

    CR

    Yes

    Nasopharyngeal

    Wound care

    Same

    Prevention of invasion

    Met

    1998

    CDDP/epi gel

    CR

    Yes

    Cervical

    Pain control

    Same

    Prevention of invasion

    Met

    5134

    CDDP/epi gel

    CR

    Yes

    Cervical

    Pain control

    Met

    Prevention of tumors breaking the skin

    Same

    1993

    CDDP/epi gel

    CR

    Yes

    Cervical

    Physical appearance

    Worsea

    Prevention of invasion

    Met

    2136

    CDDP/epi gel

    CR

    Yes

    Cervical

    Physical appearance

    Same

    Prevention of tumors breaking the skin

    Met

    1825

    CDDP/epi gel

    CR

    Yes

    Oral

    Obstructive symptom

    Same

    Pain control

    Met

    5036

    CDDP/epi gel

    CR

    Yes

    Facial

    No goal selected

    n/a

    Prevention of tumors breaking the skin

    Met

    1995

    CDDP/epi gel

    CR

    Yes

    Facial

    No goal selected

    n/a

    Prevention of invasion

    Met

    5303

    CDDP/epi gel

    CR

    Yes

    Facial

    No goal selected

    n/a

    Prevention of tumors breaking the skin

    Met

    5111

    CDDP/epi gel

    CR

    No

    Facial

    Wound care

    Same

    Wound care

    Same

    5348

    CDDP/epi gel

    CR

    No

    Cervical

    Wound care

    Same

    Wound care

    Same

    4964

    CDDP/epi gel

    CR

    No

    Cervical

    Obstructive symptom

    Same

    Obstructive symptom

    Same

    2000

    CDDP/epi gel

    CR

    No

    Cervical

    Pain control

    Same

    Prevention of tumors breaking the skin

    Unmet

    5151

    CDDP/epi gel

    CR

    No

    Facial

    No goal selected

    n/a

    Obstructive symptom

    Same

    1797

    CDDP/epi gel

    PR

    Yes

    Cranial

    No goal selected

    n/a

    Prevention of tumors breaking the skin

    Met

    5372

    CDDP/epi gel

    PR

    No

    Facial

    Physical appearance

    Same

    Obstructive symptom

    Same

    5133

    CDDP/epi gel

    PR

    No

    Oral

    Obstructive symptom

    Same

    Obstructive symptom

    Same

    5110

    CDDP/epi gel

    PR

    No

    Cervical

    Obstructive symptom

    Same

    Obstructive symptom

    Same

    1772

    CDDP/epi gel

    PR

    No

    Oral

    Pain control

    Worse

    Pain control

    Worse

    2110

    CDDP/epi gel

    PR

    No

    Oral

    Pain control

    Same

    Obstructive symptom

    Worse

    1992

    CDDP/epi gel

    PR

    No

    Cervical

    Ability to smell

    Worse

    Prevention of invasion

    Met

    aThe goal did not fail for 28 days, thereby meeting the outcome criteria for "same"

     

     

     

    Table A2-4: Treatment Goals for Patients Who Achieved an MTT Response, Study 514 Blinded Phase

    Pt.

    No.

    Treatment Group

    MTT

    Response

    Status

    Patient Benefit Achieved?

    MTT

    Location

    1 Treatment Goal Patient

    1 Treatment Goal Investigator

    Goal

    Outcome

    Goal

    Outcome

    2736

    CDDP/epi gel

    CR

    Yes

    Oral

    Wound care

    Met

    Wound care

    Met

    2735

    CDDP/epi gel

    CR

    Yes

    Oral

    Wound care

    Met

    Wound care

    Met

    5495

    Placebo

    CR

    Yes

    Cervical

    Physical appearance

    Met

    Physical appearance

    Met

    2687

    CDDP/epi gel

    CR

    Yes

    Oral

    Obstructive symptom

    Met

    Obstructive symptom

    Met

    2732

    CDDP/epi gel

    CR

    Yes

    Oral

    No goal selected

    Pain control

    Met

    5854

    CDDP/epi gel

    CR

    Yes

    Cervical

    No goal selected

    Prevention of tumors breaking skin

    Met

    2681

    CDDP/epi gel

    CR

    No

    Facial

    Physical appearance

    Same

    Physical appearance

    Same

    5565

    CDDP/epi gel

    CR

    No

    Oral

    Obstructive symptom

    Same

    Obstructive symptom

    Same

    2686

    CDDP/epi gel

    CR

    No

    Oral

    Obstructive symptom

    Not Met

    Obstructive symptom

    Not Met

    2731

    CDDP/epi gel

    CR

    No

    Facial

    Pain control

    Same

    Pain control

    Same

    2688

    CDDP/epi gel

    PR

    Yes

    Oral

    Obstructive symptom

    Met

    Obstructive symptom

    Met

    5496

    CDDP/epi gel

    PR

    No

    Oral

    Obstructive symptom

    Same

    Obstructive symptom

    Not met

    2753

    CDDP/epi gel

    PR

    No

    Oral

    Pain control

    Not Met

    Obstructive symptom

    Not Met

    2541

    CDDP/epi gel

    PR

    No

    Cervical

    Physical appearance

    Met

    Prevention of tumors breaking skin

    Not Met

    5494

    CDDP/epi gel

    PR

    No

    Oral

    Pain control

    Same

    Pain control

    Same

     

     

     

    Table A2-5: Patients Who Achieved Patient Benefit, Study 414 Blinded Phase

    Pt.

    No.

    Treatment Group

    MTT

    Response Status

    Stratum

    MTT Location

    1 Treatment Goal Patient

    1 Treatment Goal Investigator

    Goal

    Outcome

    Goal

    Outcome

    1998

    CDDP/epi gel

    CR

    1

    Cervical

    Pain control

    Same

    Prevention of invasion

    Met

    5134

    CDDP/epi gel

    CR

    1

    Cervical

    Pain control

    Met

    Prevention of tumors breaking the skin

    Same

    1825

    CDDP/epi gel

    CR

    1

    Oral

    Obstructive symptom

    Same

    Pain control

    Met

    1993

    CDDP/epi gel

    CR

    1

    Cervical

    Physical appearance

    Worsea

    Prevention of invasion

    Met

    2136

    CDDP/epi gel

    CR

    1

    Cervical

    Physical appearance

    Same

    Prevention of tumors breaking the skin

    Met

    5301

    CDDP/epi gel

    CR

    1

    Nasopharyngeal

    Wound care

    Same

    Prevention of invasion

    Met

    1995

    CDDP/epi gel

    CR

    1

    Facial

    No goal selected

    n/a

    Prevention of invasion

    Met

    5303

    CDDP/epi gel

    CR

    1

    Facial

    No goal selected

    n/a

    Prevention of tumors breaking the skin

    Met

    5036

    CDDP/epi gel

    CR

    2

    Facial

    No goal selected

    n/a

    Prevention of tumors breaking the skin

    Met

    1797

    CDDP/epi gel

    PR

    2

    Cranial

    No goal selected

    n/a

    Prevention of tumors breaking the skin

    Met

    2064

    CDDP/epi gel

    SD

    1

    Nasopharyngeal

    Ability to hear

    Same

    Prevention of invasion

    Met

    1996

    CDDP/epi gel

    SD

    1

    Cervical

    No goal selected

    n/a

    Prevention of invasion

    Met

    5253

    CDDP/epi gel

    SD

    1

    Cervical

    No goal selected

    n/a

    Prevention of tumors breaking the skin

    Met

    5278

    CDDP/epi gel

    SD

    1

    Cervical

    No goal selected

    n/a

    Prevent obstruction

    Met

    5277

    CDDP/epi gel

    SD

    1

    Facial

    Pain control

    Same

    Prevention of tumors breaking the skin

    Met

    1871

    CDDP/epi gel

    SD

    2

    Cervical

    Obstructive symptom

    Same

    Prevention of invasion

    Met

    2183

    CDDP/epi gel

    SD

    2

    Cervical

    Pain control

    Same

    Prevent obstruction

    Met

    2159

    CDDP/epi gel

    SD

    2

    Oral

    Pain control

    Met

    Pain control

    Same

    1944

    CDDP/epi gel

    PD

    1

    Laryngopharyngeal

    Pain control

    Same

    Prevent obstruction

    Met

    5302

    CDDP/epi gel

    PD

    1

    Nasopharyngeal

    Ability to see

    Same

    Prevention of tumors breaking the skin

    Met

    2157

    CDDP/epi gel

    PD

    2

    Facial

    No goal selected

    n/a

    Prevent obstruction

    Met

    1795

    CDDP/epi gel

    PD

    2

    Cervical

    No goal selected

    n/a

    Prevent obstruction

    Met

    2015

    CDDP/epi gel

    NER

    1

    Cervical

    No goal selected

    n/a

    Prevention of invasion

    Met

    5396

    CDDP/epi gel

    NER

    2

    Nasopharyngeal

    Obstructive symptom

    Same

    Prevention of invasion

    Met

    2014

    CDDP/epi gel

    NER

    2

    Facial

    No goal selected

    n/a

    Prevention of tumors breaking the skin

    Met

    a The goal did not fail for ≥28 days, thereby meeting the outcome criteria for "same"

    Table A2-6: Patients Who Achieved Patient Benefit, Study 514 Blinded Phase

    Pt.

    No.

    Treatment Group

     

    MTT

    Response

    Status

    Stratum

    MTT Location

    1 Treatment Goal Patient

    1 Treatment Goal Investigator

    Goal

    Outcome

    Goal

    Outcome

    2687

    CDDP/epi gel

    CR

    1

    Oral

    Obstructive symptom

    Met

    Obstructive symptom

    Met

    2735

    CDDP/epi gel

    CR

    1

    Oral

    Wound care

    Met

    Wound care

    Met

    2736

    CDDP/epi gel

    CR

    1

    Oral

    Wound care

    Met

    Wound care

    Met

    5495

    CDDP/epi gel

    CR

    1

    Cervical

    Physical appearance

    Met

    Physical appearance

    Met

    5854

    CDDP/epi gel

    CR

    1

    Cervical

    No goal selected

    Prevention of tumors breaking skin

    Met

    2732

    CDDP/epi gel

    CR

    2

    Oral

    No goal selected

    Pain control

    Met

    2688

    CDDP/epi gel

    PR

    1

    Oral

    Obstructive symptom

    Met

    Obstructive symptom

    Met

    2253

    Placebo

    SD

    1

    Cervical

    No goal selected

    Prevention of tumors breaking skin

    Met

    2366

    CDDP/epi gel

    SD

    2

    Facial

    Wound care

    Met

    Wound care

    Met

    2564

    CDDP/epi gel

    SD

    2

    Cervical

    Pain control

    Met

    Pain control

    Met

    2443

    Placebo

    SD

    2

    Cervical

    Obstructive symptom

    Same

    Prevent obstruction

    Met

    2421

    CDDP/epi gel

    PD

    1

    Cervical

    Pain control

    Met

    Pain control

    Same

    5421

    CDDP/epi gel

    PD

    1

    Cervical

    Pain control

    Met

    Pain control

    Same

    5588

    CDDP/epi gel

    PD

    2

    Cervical

    Wound care

    Same

    Prevention of tumors breaking skin

    Met

     

     

  3. Patient Synopses

CDDP/epi gel is a novel cancer treatment modality designed to achieve local tumor control. Following are patient profiles and photographs that illustrate the type of patients treated, the extent of previous treatment, the course of resolution of tumors, including local tissue conditions, the quality of response and the associated clinical benefits. Four of the following six patients were recorded as having both Patient Benefit and objective tumor response. Two of the patients (2137 and 5348) had evidence of other clinical benefits based upon the risks of continued tumor growth in the threatening location of these tumors or other secondary or unexpected benefits recorded. Two of these patients (2137 and 2660) illustrate the rapid tumor progression that was seen during the placebo blinded phase, yet was followed by response to open-label CDDP/epi gel. All of these patients have complex medical histories. Synopses are provided for the following patients:

Patient

Study

Randomized Treatment Group

2137*

414

Placebo

2660*

514

Placebo

5348*

414

CDDP/epi gel

1998

514

CDDP/epi gel

5134

414

CDDP/epi gel

5301

414

CDDP/epi gel

 

 

 

 

 

 

 

 

 

 

 

 

*Photographs of these patients included