Dinaciclib in Treating Patients With Stage IV Melanoma

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT00937937
• Collaborator: (none)
• Enrollment: 72
• Locations: 191
• Arm: 1
• Patients Per Site: 0.4

Study Details

Study Description

Brief Summary

This phase II trial is studying the side effects and how well dinaciclib works in treating patients with stage IV melanoma. Dinaciclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Condition or Disease	Intervention/Treatment	Phase
Acral Lentiginous Melanoma; Cutaneous Nodular Melanoma; Lentigo Maligna Melanoma; Low-CSD Melanoma; Mucosal Melanoma; Recurrent Melanoma; Stage IV Cutaneous Melanoma AJCC v6 and v7	Drug: Dinaciclib	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To assess the 1-year overall survival rate in patients with stage IV melanoma treated with dinaciclib.

SECONDARY OBJECTIVES:

1. To assess the 6-month progression-free survival rate in these patients. II. To evaluate the response rate (confirmed and unconfirmed complete and partial responses) in the subset of patients with measurable disease.

2. To assess the safety and tolerability of dinaciclib given to patients with stage IV melanoma.

OUTLINE: This is a multicenter study.

Patients receive dinaciclib IV over 2 hours on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for up to 3 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 72 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of SCH 727965 (NSC 747135) in Patients With Stage IV Melanoma
• Actual Study Start Date: Jul 1, 2009
• Actual Primary Completion Date: Oct 22, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I Patients receive dinaciclib IV over 2 hours on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.	Drug: Dinaciclib; Given IV; Other Names: CDK Inhibitor SCH 727965 MK-7965 SCH 727965

Outcome Measures

Primary Outcome Measures

1. Overall Survival [Weekly, up to 3 years]

   From date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.

Secondary Outcome Measures

1. Progression-free Survival Assessed by Response Evaluation Criteria for Solid Tumors (RECIST) [Disease assessment was performed every 6 weeks, up to 3 years.]

   Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. The duration from the date of randomization to the date of first documentation of progressive disease, symptomatic deterioration, or death dure to any cause.

2. Response Rate (Confirmed and Unconfirmed Complete and Partial Responses) Assessed by RECIST [Disease assessments for response were performed every 6 weeks, up to 3 years]

   Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

3. Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs [Toxicity assessment was evaluated after each cycle (21 days), up to 3 years.]

   Adverse Events (AEs) are reported by CTCAE Version 3.0. Only adverse events that are possibly, probably or definitely related to study drug are reported. The outcome measure here is different from Serious Adverse Event, whose definition could be more strict and specific. The number of patients who suffers the certain adverse event listed here could be larger than the number listed in following serious adverse event.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Biopsy-confirmed malignant melanoma

• Stage IV disease

• Cutaneous or mucosal origin

• Melanoma of unknown primary allowed

• No ocular melanoma

• Measurable or non-measurable disease

• No prior or concurrent brain metastases as confirmed by CT scan or MRI

• Zubrod performance status 0-1

• ANC ≥ 1,500/mm^3

• Platelet count ≥ 100,000/mm^3

• Hemoglobin ≥ 9 g/dL

• Serum bilirubin ≤ 1.5 times upper limit of normal (ULN) (including patients with hepatic metastases)

• SGOT or SGPT ≤ 2.5 times ULN (≤ 5 times ULN in the presence of hepatic metastases)

• Serum creatinine ≤ 1.5 times ULN

• Not pregnant or nursing

• Fertile patients must use effective contraception

• No other prior malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years

• No prior therapy with a cyclin-dependent kinase inhibitor

• At least 14 days since prior radiotherapy

• At least 28 days since prior systemic chemotherapy

• At least 28 days since prior adjuvant systemic therapy

• At least 28 days since prior surgery

• No more than 1 prior systemic therapy regimen (chemotherapy, biologic/immunotherapy, hormonal therapy, or a combination regimen) for stage IV melanoma and any side effects must have resolved to ≤ grade 1

• Any number of prior adjuvant systemic therapy regimens allowed, including interferon alfa-2b, GM-CSF, chemotherapy, and chemobiotherapy

• Therapy for stage IV resected free-of-disease will be considered adjuvant therapy

• Prior radiotherapy allowed provided any side effects have resolved to ≤ grade 1

• Prior surgery (for both the primary and stage IV disease) allowed provided side effects have resolved to ≤ grade 1

• No other concurrent or planned non-study treatment (including chemotherapy, hormonal therapy, biologic therapy, or radiotherapy)

• No concurrent CYP3A4 inhibitors or inducers

• No concurrent grapefruit or grapefruit juice

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Providence Hospital	Mobile	Alabama	United States	36608
2	Mercy Hospital Fort Smith	Fort Smith	Arkansas	United States	72903
3	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
4	Highlands Oncology Group - Rogers	Rogers	Arkansas	United States	72758
5	East Bay Radiation Oncology Center	Castro Valley	California	United States	94546
6	Eden Hospital Medical Center	Castro Valley	California	United States	94546
7	Valley Medical Oncology Consultants-Castro Valley	Castro Valley	California	United States	94546
8	Bay Area Breast Surgeons Inc	Emeryville	California	United States	94608
9	Valley Medical Oncology Consultants-Fremont	Fremont	California	United States	94538
10	Contra Costa Regional Medical Center	Martinez	California	United States	94553-3156
11	El Camino Hospital	Mountain View	California	United States	94040
12	Highland General Hospital	Oakland	California	United States	94602
13	Alta Bates Summit Medical Center - Summit Campus	Oakland	California	United States	94609
14	Bay Area Tumor Institute	Oakland	California	United States	94609
15	Hematology and Oncology Associates-Oakland	Oakland	California	United States	94609
16	Tom K Lee Inc	Oakland	California	United States	94609
17	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California	United States	92868
18	Valley Care Health System - Pleasanton	Pleasanton	California	United States	94588
19	Valley Medical Oncology Consultants	Pleasanton	California	United States	94588
20	Doctors Medical Center- JC Robinson Regional Cancer Center	San Pablo	California	United States	94806
21	Poudre Valley Hospital	Fort Collins	Colorado	United States	80524
22	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut	United States	06105
23	Boca Raton Comprehensive Cancer Center	Boca Raton	Florida	United States	33486
24	Orlando Health Cancer Institute	Orlando	Florida	United States	32806
25	Memorial Health University Medical Center	Savannah	Georgia	United States	31404
26	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia	United States	31405
27	South Georgia Medical Center/Pearlman Cancer Center	Valdosta	Georgia	United States	31602
28	Saint Anthony's Health	Alton	Illinois	United States	62002
29	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois	United States	62526
30	Decatur Memorial Hospital	Decatur	Illinois	United States	62526
31	Advocate Good Samaritan Hospital	Downers Grove	Illinois	United States	60515
32	Loyola University Medical Center	Maywood	Illinois	United States	60153
33	Good Samaritan Regional Health Center	Mount Vernon	Illinois	United States	62864
34	Memorial Medical Center	Springfield	Illinois	United States	62781
35	Franciscan Saint Francis Health-Beech Grove	Beech Grove	Indiana	United States	46107
36	Reid Health	Richmond	Indiana	United States	47374
37	Cancer Center of Kansas - Chanute	Chanute	Kansas	United States	66720
38	Cancer Center of Kansas - Dodge City	Dodge City	Kansas	United States	67801
39	Cancer Center of Kansas - El Dorado	El Dorado	Kansas	United States	67042
40	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas	United States	66701
41	HaysMed University of Kansas Health System	Hays	Kansas	United States	67601
42	Hutchinson Regional Medical Center	Hutchinson	Kansas	United States	67502
43	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
44	University of Kansas Cancer Center	Kansas City	Kansas	United States	66160
45	Cancer Center of Kansas-Kingman	Kingman	Kansas	United States	67068
46	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
47	Southwest Medical Center	Liberal	Kansas	United States	67901
48	Cancer Center of Kansas-Liberal	Liberal	Kansas	United States	67905
49	Cancer Center of Kansas - Newton	Newton	Kansas	United States	67114
50	Olathe Cancer Center	Olathe	Kansas	United States	66061
51	Menorah Medical Center	Overland Park	Kansas	United States	66209
52	Saint Luke's South Hospital	Overland Park	Kansas	United States	66213
53	Cancer Center of Kansas - Parsons	Parsons	Kansas	United States	67357
54	Ascension Via Christi - Pittsburg	Pittsburg	Kansas	United States	66762
55	Kansas City NCI Community Oncology Research Program	Prairie Village	Kansas	United States	66208
56	Cancer Center of Kansas - Pratt	Pratt	Kansas	United States	67124
57	Cancer Center of Kansas - Salina	Salina	Kansas	United States	67401
58	Salina Regional Health Center	Salina	Kansas	United States	67401
59	Advent Health - Shawnee Mission Medical Center	Shawnee Mission	Kansas	United States	66204
60	Cotton O'Neil Cancer Center / Stormont Vail Health	Topeka	Kansas	United States	66606
61	University of Kansas Health System Saint Francis Campus	Topeka	Kansas	United States	66606
62	Cancer Center of Kansas - Wellington	Wellington	Kansas	United States	67152
63	Associates In Womens Health	Wichita	Kansas	United States	67208
64	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas	United States	67208
65	Ascension Via Christi Hospitals Wichita	Wichita	Kansas	United States	67214
66	Cancer Center of Kansas - Wichita	Wichita	Kansas	United States	67214
67	Wichita NCI Community Oncology Research Program	Wichita	Kansas	United States	67214
68	Cancer Center of Kansas - Winfield	Winfield	Kansas	United States	67156
69	Baton Rouge General Medical Center	Baton Rouge	Louisiana	United States	70806
70	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana	United States	70809
71	Louisiana State University Health Science Center	New Orleans	Louisiana	United States	70112
72	University Medical Center New Orleans	New Orleans	Louisiana	United States	70112
73	Boston Medical Center	Boston	Massachusetts	United States	02118
74	Michigan Cancer Research Consortium NCORP	Ann Arbor	Michigan	United States	48106
75	Saint Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106
76	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109
77	Bronson Battle Creek	Battle Creek	Michigan	United States	49017
78	Spectrum Health Big Rapids Hospital	Big Rapids	Michigan	United States	49307
79	Beaumont Hospital - Dearborn	Dearborn	Michigan	United States	48124
80	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan	United States	48201
81	Ascension Saint John Hospital	Detroit	Michigan	United States	48236
82	Hurley Medical Center	Flint	Michigan	United States	48503
83	Genesys Regional Medical Center-West Flint Campus	Flint	Michigan	United States	48532
84	Cancer Research Consortium of West Michigan NCORP	Grand Rapids	Michigan	United States	49503
85	Mercy Health Saint Mary's	Grand Rapids	Michigan	United States	49503
86	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan	United States	49503
87	Allegiance Health	Jackson	Michigan	United States	49201
88	Sparrow Hospital	Lansing	Michigan	United States	48912
89	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan	United States	48154
90	Mercy Health Mercy Campus	Muskegon	Michigan	United States	49444
91	Saint Joseph Mercy Oakland	Pontiac	Michigan	United States	48341
92	Lake Huron Medical Center	Port Huron	Michigan	United States	48060
93	Ascension Saint Mary's Hospital	Saginaw	Michigan	United States	48601
94	Munson Medical Center	Traverse City	Michigan	United States	49684
95	Saint John Macomb-Oakland Hospital	Warren	Michigan	United States	48093
96	Metro Health Hospital	Wyoming	Michigan	United States	49519
97	Saint Francis Medical Center	Cape Girardeau	Missouri	United States	63703
98	Truman Medical Centers	Kansas City	Missouri	United States	64108
99	Saint Luke's Hospital of Kansas City	Kansas City	Missouri	United States	64111
100	Saint Joseph Health Center	Kansas City	Missouri	United States	64114
101	North Kansas City Hospital	Kansas City	Missouri	United States	64116
102	Heartland Hematology and Oncology Associates Incorporated	Kansas City	Missouri	United States	64118
103	Research Medical Center	Kansas City	Missouri	United States	64132
104	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri	United States	64086
105	Liberty Radiation Oncology Center	Liberty	Missouri	United States	64068
106	Heartland Regional Medical Center	Saint Joseph	Missouri	United States	64506
107	Saint Joseph Oncology Inc	Saint Joseph	Missouri	United States	64507
108	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri	United States	63109
109	Mercy Hospital Saint Louis	Saint Louis	Missouri	United States	63141
110	Saint Louis-Cape Girardeau CCOP	Saint Louis	Missouri	United States	63141
111	Billings Clinic Cancer Center	Billings	Montana	United States	59101
112	Northern Rockies Radiation Oncology Center	Billings	Montana	United States	59101
113	Saint Vincent Healthcare	Billings	Montana	United States	59101
114	Montana Cancer Consortium NCORP	Billings	Montana	United States	59102
115	Saint Vincent Frontier Cancer Center	Billings	Montana	United States	59102
116	Bozeman Deaconess Hospital	Bozeman	Montana	United States	59715
117	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana	United States	59701
118	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana	United States	59405
119	Berdeaux, Donald MD (UIA Investigator)	Great Falls	Montana	United States	59405
120	Great Falls Clinic	Great Falls	Montana	United States	59405
121	Northern Montana Hospital	Havre	Montana	United States	59501
122	Saint Peter's Community Hospital	Helena	Montana	United States	59601
123	Glacier Oncology PLLC	Kalispell	Montana	United States	59901
124	Kalispell Medical Oncology	Kalispell	Montana	United States	59901
125	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
126	Montana Cancer Specialists	Missoula	Montana	United States	59802
127	Saint Patrick Hospital - Community Hospital	Missoula	Montana	United States	59802
128	Community Medical Hospital	Missoula	Montana	United States	59804
129	Guardian Oncology and Center for Wellness	Missoula	Montana	United States	59804
130	University Medical Center of Southern Nevada	Las Vegas	Nevada	United States	89102
131	Nevada Cancer Institute-Summerlin Campus	Las Vegas	Nevada	United States	89135
132	University of Rochester	Rochester	New York	United States	14642
133	Novant Health Presbyterian Medical Center	Charlotte	North Carolina	United States	28204
134	Wayne Memorial Hospital	Goldsboro	North Carolina	United States	27534
135	FirstHealth of the Carolinas-Moore Regional Hospital	Pinehurst	North Carolina	United States	28374
136	Southeast Clinical Oncology Research Consortium NCORP	Winston-Salem	North Carolina	United States	27104
137	Grandview Hospital	Dayton	Ohio	United States	45405
138	Good Samaritan Hospital - Dayton	Dayton	Ohio	United States	45406
139	Miami Valley Hospital	Dayton	Ohio	United States	45409
140	Miami Valley Hospital North	Dayton	Ohio	United States	45415
141	Dayton NCI Community Oncology Research Program	Dayton	Ohio	United States	45459
142	Blanchard Valley Hospital	Findlay	Ohio	United States	45840
143	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
144	Wayne Hospital	Greenville	Ohio	United States	45331
145	Kettering Medical Center	Kettering	Ohio	United States	45429
146	Upper Valley Medical Center	Troy	Ohio	United States	45373
147	Clinton Memorial Hospital	Wilmington	Ohio	United States	45177
148	Greene Memorial Hospital	Xenia	Ohio	United States	45385
149	Saint Charles Health System	Bend	Oregon	United States	97701
150	Providence Milwaukie Hospital	Milwaukie	Oregon	United States	97222
151	Providence Portland Medical Center	Portland	Oregon	United States	97213
152	Adventist Medical Center	Portland	Oregon	United States	97216
153	Providence Saint Vincent Medical Center	Portland	Oregon	United States	97225
154	Salem Hospital	Salem	Oregon	United States	97301
155	Prisma Health Cancer Institute - Spartanburg	Boiling Springs	South Carolina	United States	29316
156	Prisma Health Cancer Institute - Easley	Easley	South Carolina	United States	29640
157	McLeod Regional Medical Center	Florence	South Carolina	United States	29506
158	Greenville Health System Cancer Institute-Andrews	Greenville	South Carolina	United States	29601
159	Saint Francis Hospital	Greenville	South Carolina	United States	29601
160	Prisma Health Cancer Institute - Butternut	Greenville	South Carolina	United States	29605
161	Prisma Health Cancer Institute - Faris	Greenville	South Carolina	United States	29605
162	Prisma Health Greenville Memorial Hospital	Greenville	South Carolina	United States	29605
163	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina	United States	29615
164	Self Regional Healthcare	Greenwood	South Carolina	United States	29646
165	Prisma Health Cancer Institute - Greer	Greer	South Carolina	United States	29650
166	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina	United States	29672
167	Wellmont Holston Valley Hospital and Medical Center	Kingsport	Tennessee	United States	37660
168	Thompson Cancer Survival Center	Knoxville	Tennessee	United States	37916
169	Medical City Dallas Hospital	Dallas	Texas	United States	75230
170	Scott and White Memorial Hospital	Temple	Texas	United States	76508
171	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah	United States	84112
172	Danville Regional Medical Center	Danville	Virginia	United States	24541
173	Sovah Health Martinsville	Martinsville	Virginia	United States	24115
174	Southwest VA Regional Cancer Center	Norton	Virginia	United States	24273
175	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington	United States	98225
176	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington	United States	98310
177	Kadlec Clinic Hematology and Oncology	Kennewick	Washington	United States	99336
178	Skagit Valley Hospital	Mount Vernon	Washington	United States	98274
179	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington	United States	98370
180	Harborview Medical Center	Seattle	Washington	United States	98104
181	Minor and James Medical PLLC	Seattle	Washington	United States	98104
182	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
183	Kaiser Permanente Washington	Seattle	Washington	United States	98112
184	Swedish Medical Center-First Hill	Seattle	Washington	United States	98122-4307
185	University of Washington Medical Center - Montlake	Seattle	Washington	United States	98195
186	Cancer Care Northwest - Spokane South	Spokane	Washington	United States	99202
187	Evergreen Hematology and Oncology PS	Spokane	Washington	United States	99218
188	PeaceHealth Southwest Medical Center	Vancouver	Washington	United States	98664
189	Wenatchee Valley Hospital and Clinics	Wenatchee	Washington	United States	98801
190	Rocky Mountain Oncology	Casper	Wyoming	United States	82609
191	Welch Cancer Center	Sheridan	Wyoming	United States	82801

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Christopher D Lao, Southwest Oncology Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00937937
• Other Study ID Numbers: NCI-2011-01935; NCI-2011-01935; SWOG-S0826; CDR0000647155; S0826; S0826; U10CA032102
• First Posted: Jul 13, 2009
• Last Update Posted: Jul 21, 2022
• Last Verified: Jun 1, 2022

• Additional relevant MeSH terms: Melanoma; Hutchinson's Melanotic Freckle; Lentigo

Study Results

Participant Flow

Arm/Group Title	Dinaciclib
Arm/Group Description	Patients receive dinaciclib IV over 2 hours on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
Period Title: Overall Study
STARTED	72
COMPLETED	0
NOT COMPLETED	72

Baseline Characteristics

Arm/Group Title	Dinaciclib
Arm/Group Description	Patients receive dinaciclib IV over 2 hours on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
Overall Participants	72
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	65.4
Sex: Female, Male (Count of Participants)
Female	20 27.8%
Male	52 72.2%
Race/Ethnicity, Customized (participants) [Number]
White	69 95.8%
Asian	2 2.8%
Pacific Islander	1 1.4%
Hispanic (participants) [Number]
Yes	2 2.8%
No	69 95.8%
Unknown	1 1.4%
Performance Status (participants) [Number]
0	38 52.8%
1	34 47.2%
Site(s) of Metastases (participants) [Number]
Bone	18 25%
Brain	0 0%
Liver	23 31.9%
Lymph node, soft tissue, skin	41 56.9%
Lung	41 56.9%
Other visceral	17 23.6%
Other non-visceral	14 19.4%
Elevated LDH (participants) [Number]
No	41 56.9%
Yes	31 43.1%
Primary Type (participants) [Number]
Cutaneous	55 76.4%
Mucosal	8 11.1%
Unknown primary	9 12.5%

Outcome Measures

1. Primary Outcome

Title	Overall Survival
Description	From date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.
Time Frame	Weekly, up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dinaciclib
Arm/Group Description	Patients receive dinaciclib IV over 2 hours on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	72
Median (95% Confidence Interval) [months]	8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dinaciclib
	Comments	one-year overall survival estimate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	1-year overall survival estimate
	Estimated Value	0.38
	Confidence Interval	(2-Sided) 95%; 0.27 to 0.49
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Progression-free Survival Assessed by Response Evaluation Criteria for Solid Tumors (RECIST)
Description	Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. The duration from the date of randomization to the date of first documentation of progressive disease, symptomatic deterioration, or death dure to any cause.
Time Frame	Disease assessment was performed every 6 weeks, up to 3 years.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dinaciclib
Arm/Group Description	Patients receive dinaciclib IV over 2 hours on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	72
Median (95% Confidence Interval) [months]	1.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dinaciclib
	Comments	6-month PFS estimate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	6-month PFS estimate
	Estimated Value	0.07
	Confidence Interval	(2-Sided) 95%; 0.03 to 0.15
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Response Rate (Confirmed and Unconfirmed Complete and Partial Responses) Assessed by RECIST
Description	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame	Disease assessments for response were performed every 6 weeks, up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dinaciclib
Arm/Group Description	Patients receive dinaciclib IV over 2 hours on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	72
Mean (95% Confidence Interval) [percentage of participants]	0 0%

4. Secondary Outcome

Title	Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs
Description	Adverse Events (AEs) are reported by CTCAE Version 3.0. Only adverse events that are possibly, probably or definitely related to study drug are reported. The outcome measure here is different from Serious Adverse Event, whose definition could be more strict and specific. The number of patients who suffers the certain adverse event listed here could be larger than the number listed in following serious adverse event.
Time Frame	Toxicity assessment was evaluated after each cycle (21 days), up to 3 years.

Outcome Measure Data

Analysis Population Description

Eligible patients who had received the protocol treatments were included in the adverse event summaries. Any CTCAE 3.0 event of Grade 3 (serious), Grade 4 (life threatening) or Grade 5 (fatal) which were deemed to be related to protocol treatment are included.

Arm/Group Title	Dinaciclib
Arm/Group Description
Measure Participants	72
AST, SGOT	1 1.4%
Cardiac troponin I (cTnI)	1 1.4%
Cardiac-ischemia/infarction	1 1.4%
Constitutional Symptoms-Other (Specify)	1 1.4%
Dehydration	1 1.4%
Diarrhea	11 15.3%
Dyspnea (shortness of breath)	1 1.4%
Edema: limb	1 1.4%
Fatigue (asthenia, lethargy, malaise)	3 4.2%
Febrile neutropenia	2 2.8%
Hypotension	2 2.8%
Hypoxia	1 1.4%
Leukocytes (total WBC)	18 25%
Lymphopenia	5 6.9%
Metabolic/Laboratory-Other (Specify)	2 2.8%
Mucositis/stomatitis (clinical exam) - Oral cavity	1 1.4%
Muscle weakness, not d/t neuropathy - body/general	1 1.4%
Nausea	1 1.4%
Neutrophils/granulocytes (ANC/AGC)	36 50%
Ocular/Visual-Other (Specify)	1 1.4%
PTT (Partial thromboplastin time)	1 1.4%
Pain - Abdomen NOS	2 2.8%
Pain - Back	1 1.4%
Pain - Cardiac/heart	1 1.4%
Pain - Extremity-limb	1 1.4%
Pain - Head/headache	1 1.4%
Pain - Tumor pain	1 1.4%
Prolonged QTc interval	1 1.4%
Renal failure	1 1.4%
SVT and nodal arrhythmia - Atrial fibrillation	1 1.4%
SVT and nodal arrhythmia - Atrial flutter	1 1.4%
SVT and nodal arrhythmia - Sinus tachycardia	1 1.4%
Sodium, serum-low (hyponatremia)	1 1.4%
Somnolence/depressed level of consciousness	1 1.4%
Syncope (fainting)	1 1.4%
Thrombosis/thrombus/embolism	1 1.4%
Vascular-Other (Specify)	1 1.4%
Vision-blurred vision	1 1.4%
Vomiting	1 1.4%

Adverse Events

Time Frame	Toxicity assessment was evaluated after each cycle (21 days), up to 3 years.
Arm/Group Title	SCH 727965
Arm/Group Description
All Cause Mortality
	SCH 727965
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	SCH 727965
	Affected / at Risk (%)	# Events
Total	30/72 (41.7%)
Blood and lymphatic system disorders
Febrile neutropenia	1/72 (1.4%)
Hemoglobin	1/72 (1.4%)
Cardiac disorders
Pain - Cardiac/heart	1/72 (1.4%)
SVT and nodal arrhythmia - Atrial fibrillation	2/72 (2.8%)
Eye disorders
Ocular/Visual-Other	1/72 (1.4%)
Vision-blurred vision	1/72 (1.4%)
Gastrointestinal disorders
Diarrhea	1/72 (1.4%)
Pain - Abdomen NOS	1/72 (1.4%)
General disorders
Death not associated with CTCAE term - Death NOS	1/72 (1.4%)
Edema: limb	1/72 (1.4%)
Edema: trunk/genital	1/72 (1.4%)
Pain - Chest/thorax NOS	1/72 (1.4%)
Pain-Other	2/72 (2.8%)
Injury, poisoning and procedural complications
Fracture	1/72 (1.4%)
Investigations
AST, SGOT	1/72 (1.4%)
Alkaline phosphatase	1/72 (1.4%)
Cardiac troponin I (cTnI)	1/72 (1.4%)
Leukocytes (total WBC)	2/72 (2.8%)
Lymphopenia	1/72 (1.4%)
Neutrophils/granulocytes (ANC/AGC)	13/72 (18.1%)
Metabolism and nutrition disorders
Calcium, serum-low (hypocalcemia)	1/72 (1.4%)
Dehydration	3/72 (4.2%)
Phosphate, serum-low (hypophosphatemia)	1/72 (1.4%)
Sodium, serum-low (hyponatremia)	2/72 (2.8%)
Musculoskeletal and connective tissue disorders
Muscle weakness, not d/t neuropathy - body/general	1/72 (1.4%)
Pain - Back	1/72 (1.4%)
Pain - Extremity-limb	1/72 (1.4%)
Trismus (diff, restriction, pain opening mouth)	1/72 (1.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Death - Disease progression NOS	8/72 (11.1%)
Pain - Tumor pain	2/72 (2.8%)
Nervous system disorders
Neuropathy: motor	1/72 (1.4%)
Neuropathy: sensory	1/72 (1.4%)
Ocular/Visual-Other	1/72 (1.4%)
Pain - Head/headache	1/72 (1.4%)
Somnolence/depressed level of consciousness	1/72 (1.4%)
Syncope (fainting)	1/72 (1.4%)
Renal and urinary disorders
Renal failure	1/72 (1.4%)
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)	3/72 (4.2%)
Hypoxia	1/72 (1.4%)
Pleural effusion (non-malignant)	1/72 (1.4%)
Vascular disorders
Hypotension	3/72 (4.2%)
Thrombosis/thrombus/embolism	1/72 (1.4%)
Vascular-Other	1/72 (1.4%)
Other (Not Including Serious) Adverse Events
	SCH 727965
	Affected / at Risk (%)	# Events
Total	64/72 (88.9%)
Blood and lymphatic system disorders
Hemoglobin	30/72 (41.7%)
Eye disorders
Vision-blurred vision	4/72 (5.6%)
Gastrointestinal disorders
Constipation	18/72 (25%)
Diarrhea	43/72 (59.7%)
Heartburn/dyspepsia	4/72 (5.6%)
Mucositis/stomatitis (clinical exam) - Oral cavity	5/72 (6.9%)
Nausea	42/72 (58.3%)
Pain - Abdomen NOS	10/72 (13.9%)
Vomiting	30/72 (41.7%)
General disorders
Edema: limb	8/72 (11.1%)
Fatigue (asthenia, lethargy, malaise)	45/72 (62.5%)
Fever in absence of neutropenia, ANC lt1.0x10e9/L	7/72 (9.7%)
Rigors/chills	7/72 (9.7%)
Infections and infestations
Infection-Other	5/72 (6.9%)
Investigations
ALT, SGPT (serum glutamic pyruvic transaminase)	9/72 (12.5%)
AST, SGOT	9/72 (12.5%)
Alkaline phosphatase	8/72 (11.1%)
Bilirubin (hyperbilirubinemia)	4/72 (5.6%)
Creatinine	9/72 (12.5%)
Leukocytes (total WBC)	40/72 (55.6%)
Lymphopenia	13/72 (18.1%)
Metabolic/Laboratory-Other	5/72 (6.9%)
Neutrophils/granulocytes (ANC/AGC)	41/72 (56.9%)
Platelets	4/72 (5.6%)
Weight loss	4/72 (5.6%)
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia)	12/72 (16.7%)
Anorexia	16/72 (22.2%)
Calcium, serum-low (hypocalcemia)	8/72 (11.1%)
Dehydration	5/72 (6.9%)
Glucose, serum-high (hyperglycemia)	14/72 (19.4%)
Potassium, serum-low (hypokalemia)	6/72 (8.3%)
Sodium, serum-low (hyponatremia)	8/72 (11.1%)
Musculoskeletal and connective tissue disorders
Muscle weakness, not d/t neuropathy - body/general	4/72 (5.6%)
Pain - Back	12/72 (16.7%)
Pain - Extremity-limb	7/72 (9.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pain - Tumor pain	6/72 (8.3%)
Nervous system disorders
Dizziness	5/72 (6.9%)
Neuropathy: sensory	4/72 (5.6%)
Pain - Head/headache	7/72 (9.7%)
Taste alteration (dysgeusia)	8/72 (11.1%)
Psychiatric disorders
Mood alteration - depression	5/72 (6.9%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	6/72 (8.3%)
Cough	16/72 (22.2%)
Dyspnea (shortness of breath)	8/72 (11.1%)
Skin and subcutaneous tissue disorders
Dermatology/Skin-Other	4/72 (5.6%)
Hair loss/Alopecia (scalp or body)	11/72 (15.3%)
Rash/desquamation	6/72 (8.3%)
Sweating (diaphoresis)	7/72 (9.7%)
Vascular disorders
Hypotension	16/72 (22.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.