Dinaciclib in Treating Patients With Stage III-IV Melanoma

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Terminated
• CT.gov ID: NCT01026324
• Collaborator: (none)
• Enrollment: 12
• Location: 1
• Arm: 1
• Actual Duration (Months): 61
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is a phase I/II trial is studying the side effects and best dose of dinaciclib and to see how well it works in treating patients with advanced 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
Stage IIIB Melanoma; Stage IIIC Melanoma; Stage IV Melanoma	Drug: dinaciclib; Other: pharmacological study; Other: laboratory biomarker analysis	Phase 1/Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To determine the recommended phase 2 dose of SCH727965 administered as a 4-hour infusion every other week in patients with advanced malignant melanoma. (Phase I) II. To determine the 1-year overall survival of patients with malignant melanoma treated with SCH727965 at the dose and schedule derived in the phase 1 part of the study. (Phase II)

SECONDARY OBJECTIVES:

1. To characterize the safety profile and toxicities of SCH727965 administered as a 4-hour infusion every other week.

2. To determine the pharmacokinetics of SCH727965 administered as a 4-hour infusion every other week.

3. To determine the proportion of patients with malignant melanoma who are alive without progression of disease 6 months after beginning treatment with SCH727965 at the dose and schedule derived in the phase 1 part of the study.

4. To determine the objective response rate to SCH727965 of patients with malignant melanoma enrolled to part 2 of the study.

5. To document cdk2, combined cdk2/1 and cdk9 inhibition in surrogate tissues and tumor.

6. To correlate the degree of change of pharmacodynamic parameters in post-treatment compared to pre-treatment samples with clinical outcome.

7. To correlate the degree of change of parameters defining cdk2, cdk2/1 and cdk9 inhibition with pharmacokinetic parameters.

8. To correlate pre-treatment cdk2 levels with the degree of change of parameters measuring cdk2 inhibition.

9. To correlate pre-treatment cdk2 levels with clinical outcome. X. To correlate tumor p53 status with clinical outcome.

OUTLINE: This is a phase I dose-escalation study followed by a phase II study.

Patients receive dinaciclib IV over 4 hours on day 1. Courses repeat every 14 days in the absence of disease progression and unacceptable toxicity.

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2 Study of SCH727965 in Patients With Malignant Melanoma
• Actual Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: Oct 1, 2014
• Actual Study Completion Date: Oct 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (dinaciclib) Patients receive dinaciclib IV over 4 hours on day 1. Courses repeat every 14 days in the absence of disease progression and unacceptable toxicity.	Drug: dinaciclib; Given IV; Other Names: CDK inhibitor SCH 727965 cyclin-dependent kinase inhibitor SCH 727965 SCH 727965 ; Other: pharmacological study; Correlative studies; Other Names: pharmacological studies ; Other: laboratory biomarker analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Recommended Phase-2 Dose of SCH727965 [14 days]

   Due to difficult accrual to the trial, enrollment was ended early without determination of an MTD.

2. Percentage of Patients Alive (Phase II) [Up to 1 year]

   Due to difficult accrual to the trial, enrollment was ended early without entering into Phase II

Secondary Outcome Measures

1. Progression-free Survival [Up to 6 months]

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 histologically confirmed, unresectable stage III or stage IV malignant melanoma

• ECOG performance status =< 1

• Absolute neutrophil count >= 1.5 x 10^9/L

• Platelets >= 100 x 10^9/L

• Total bilirubin within normal institutional limits

• AST(SGOT)/ALT(SGPT =< 1.5 x institutional upper limit of normal

• Creatinine =< 1.5 mg/dl OR

• Creatinine clearance >= 50 mL/min for patients with creatinine levels above institutional normal

• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

• Eligible patients must agree to pre- and post-treatment biopsies of normal skin; in the phase 1 part of the study, patients with cutaneous disease or accessible lymph nodes must also agree to pre- and post-treatment tumor biopsies; in the phase 2 part of the study, tumor biopsies are required of the first 20 patients enrolled who have cutaneous disease or accessible lymph nodes

• Patients enrolled to the Phase 2 portion of the study must have measurable disease by RECIST criteria

• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Patients who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier

• Patients may not be receiving any other investigational agents

• Patients with active CNS metastases are excluded; patients with a history of CNS metastases that have been treated must be stable for 4 weeks after completion of treatment, with image documentation required; patients must not be taking enzyme-inducing anticonvulsants and must be either off steroids or be receiving a stable dose of steroids

• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with SCH727965

• HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with SCH727965; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated

• Patients with other currently active malignancies are excluded, except those with an in-situ cancer or basal or squamous cell carcinoma of the skin

• In the phase 2 part of the study, patients who have received prior investigational treatment with a cdk inhibitor are excluded

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Frank Hodi, Dana-Farber Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01026324
• Other Study ID Numbers: NCI-2013-00522; NCI-2013-00522; 09-152; 8296; U01CA062490; P30CA006516
• First Posted: Dec 4, 2009
• Last Update Posted: Apr 4, 2017
• Last Verified: Mar 1, 2017

• Additional relevant MeSH terms: Melanoma; Cyclin-Dependent Kinase Inhibitor Proteins

Study Results

Participant Flow

Recruitment Details	Subjects were screened and enrolled at one site in the US, Dana Farber Cancer Institute.

Arm/Group Title	Treatment (Dinaciclib) Dose Level 1	Treatment (Dinaciclib) Dose Level 2	Treatment (Dinaciclib) Dose Level 3
Arm/Group Description	Patients receive dinaciclib at Dose Level 1 (10 mg/m2 IV) over 4 hours on day 1. Courses repeat every 14 days in the absence of disease progression and unacceptable toxicity. dinaciclib: Given IV pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies	Patients receive dinaciclib at Dose Level 2 (20 mg/m2 IV) over 4 hours on day 1. Courses repeat every 14 days in the absence of disease progression and unacceptable toxicity. dinaciclib: Given IV pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies	Patients receive dinaciclib at Dose Level 3(30 mg/m2 IV) over 4 hours on day 1. Courses repeat every 14 days in the absence of disease progression and unacceptable toxicity. dinaciclib: Given IV pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies
Period Title: Treatment Allocation
STARTED	5	3	4
Discontinued Intervention (Toxicity)	1	0	0
Discontinuted Intervention (Progression)	3	3	4
Discontinued Intervention (Withdrew)	1	0	0
COMPLETED	5	3	4
NOT COMPLETED	0	0	0
Period Title: Treatment Allocation
STARTED	5	3	4
Follow up Discontinuation (Death)	4	3	4
COMPLETED	4	3	4
NOT COMPLETED	1	0	0

Baseline Characteristics

Arm/Group Title	Treatment (Dinaciclib) Dose Level 1	Treatment (Dinaciclib) Dose Level 2	Treatment (Dinaciclib) Dose Level 3	Total
Arm/Group Description	Patients receive dinaciclib at Dose Level 1 (10 mg/m2 IV) over 4 hours on day 1. Courses repeat every 14 days in the absence of disease progression and unacceptable toxicity. dinaciclib: Given IV pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies	Patients receive dinaciclib at Dose Level 2 (20 mg/m2 IV) over 4 hours on day 1. Courses repeat every 14 days in the absence of disease progression and unacceptable toxicity. dinaciclib: Given IV pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies	Patients receive dinaciclib at Dose Level 3 (30 mg/m2 IV) over 4 hours on day 1. Courses repeat every 14 days in the absence of disease progression and unacceptable toxicity. dinaciclib: Given IV pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies	Total of all reporting groups
Overall Participants	5	3	4	12
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	4 80%	2 66.7%	4 100%	10 83.3%
>=65 years	1 20%	1 33.3%	0 0%	2 16.7%
Sex: Female, Male (Count of Participants)
Female	2 40%	2 66.7%	1 25%	5 41.7%
Male	3 60%	1 33.3%	3 75%	7 58.3%

Outcome Measures

1. Primary Outcome

Title	Recommended Phase-2 Dose of SCH727965
Description	Due to difficult accrual to the trial, enrollment was ended early without determination of an MTD.
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

Due to difficult accrual to the trial, enrollment was ended early without determination of an MTD.

Arm/Group Title	Treatment (Dinaciclib)
Arm/Group Description	Patients receive dinaciclib IV over 4 hours on day 1. Courses repeat every 14 days in the absence of disease progression and unacceptable toxicity. dinaciclib: Given IV
Measure Participants	0

2. Primary Outcome

Title	Percentage of Patients Alive (Phase II)
Description	Due to difficult accrual to the trial, enrollment was ended early without entering into Phase II
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

Due to difficult accrual to the trial, enrollment was ended early without entering into Phase II

Arm/Group Title	Treatment (Dinaciclib)
Arm/Group Description	Patients receive dinaciclib IV over 4 hours on day 1. Courses repeat every 14 days in the absence of disease progression and unacceptable toxicity. dinaciclib: Given IV
Measure Participants	0

3. Secondary Outcome

Title	Progression-free Survival
Time Frame	Up to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Dinaciclib) Dose Level 1	Treatment (Dinaciclib) Dose Level 2	Treatment (Dinaciclib) Dose Level 3
Arm/Group Description	Patients receive dinaciclib at Dose Level 1 (10 mg/m2 IV) over 4 hours on day 1. Courses repeat every 14 days in the absence of disease progression and unacceptable toxicity. dinaciclib: Given IV	Patients receive dinaciclib at Dose Level 2 (20 mg/m2 IV) over 4 hours on day 1. Courses repeat every 14 days in the absence of disease progression and unacceptable toxicity. dinaciclib: Given IV	Patients receive dinaciclib at Dose Level 3 (30 mg/m2 IV) over 4 hours on day 1. Courses repeat every 14 days in the absence of disease progression and unacceptable toxicity. dinaciclib: Given IV
Measure Participants	5	3	4
Stable Disease	2 40%	0 0%	0 0%
Progressive Disease	1 20%	3 100%	4 100%
Unevaluable	2 40%	0 0%	0 0%

Adverse Events

Arm/Group Title	Dose Level 1 - Treatment (Dinaciclib)		Dose Level 2 - Treatment (Dinaciclib)		Dose Level 3 - Treatment (Dinaciclib)
Arm/Group Description	Patients receive dinaciclib IV over 4 hours on Day 1. Courses repeat every 14 days in the absence of disease progression and unacceptable toxicity. Dose: 10 MG/M2 Dinaciclib: Given IV Pharmacological study: Correlative studies Laboratory biomarker analysis: Correlative studies		Patients receive dinaciclib IV over 4 hours on Day 1. Courses repeat every 14 days in the absence of disease progression and unacceptable toxicity. Dose: 20 MG/M2 Dinaciclib: Given IV Pharmacological study: Correlative studies Laboratory biomarker analysis: Correlative studies		Patients receive dinaciclib IV over 4 hours on Day 1. Courses repeat every 14 days in the absence of disease progression and unacceptable toxicity. Dose: 30 MG/M2 Dinaciclib: Given IV Pharmacological study: Correlative studies Laboratory biomarker analysis: Correlative studies
All Cause Mortality
	Dose Level 1 - Treatment (Dinaciclib)		Dose Level 2 - Treatment (Dinaciclib)		Dose Level 3 - Treatment (Dinaciclib)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/5 (100%)		3/3 (100%)		4/4 (100%)
Serious Adverse Events
	Dose Level 1 - Treatment (Dinaciclib)		Dose Level 2 - Treatment (Dinaciclib)		Dose Level 3 - Treatment (Dinaciclib)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/5 (100%)		3/3 (100%)		4/4 (100%)
Blood and lymphatic system disorders
Leukocytes	1/5 (20%)		1/3 (33.3%)		3/4 (75%)
Neutrophils	1/5 (20%)		3/3 (100%)		4/4 (100%)
Lymphopenia	0/5 (0%)		3/3 (100%)		2/4 (50%)
Gastrointestinal disorders
Dehydration	0/5 (0%)		1/3 (33.3%)		0/4 (0%)
Metabolism and nutrition disorders
Hyperuricemia	0/5 (0%)		1/3 (33.3%)		1/4 (25%)
Hyponatremia	1/5 (20%)		0/3 (0%)		0/4 (0%)
Hypophosphatemia	1/5 (20%)		1/3 (33.3%)		1/4 (25%)
Nervous system disorders
Syncope	0/5 (0%)		1/3 (33.3%)		0/4 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/5 (20%)		0/3 (0%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	Dose Level 1 - Treatment (Dinaciclib)		Dose Level 2 - Treatment (Dinaciclib)		Dose Level 3 - Treatment (Dinaciclib)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/5 (100%)		3/3 (100%)		4/4 (100%)
Blood and lymphatic system disorders
Hemoglobin	2/5 (40%)		1/3 (33.3%)		1/4 (25%)
Leukocytes	2/5 (40%)		3/3 (100%)		4/4 (100%)
Lymphopenia	2/5 (40%)		3/3 (100%)		2/4 (50%)
Neutrophils	1/5 (20%)		3/3 (100%)		4/4 (100%)
Edema limb	1/5 (20%)		0/3 (0%)		0/4 (0%)
Hyperkalemia	0/5 (0%)		1/3 (33.3%)		0/4 (0%)
Hypoalbuminemia	2/5 (40%)		1/3 (33.3%)		0/4 (0%)
Hypocalcemia	2/5 (40%)		2/3 (66.7%)		2/4 (50%)
Hypokalemia	3/5 (60%)		0/3 (0%)		1/4 (25%)
Hypomagnesemia	1/5 (20%)		1/3 (33.3%)		2/4 (50%)
Hyponatremia	2/5 (40%)		0/3 (0%)		0/4 (0%)
Hypophosphatemia	2/5 (40%)		3/3 (100%)		1/4 (25%)
Cardiac disorders
Hypertension	1/5 (20%)		0/3 (0%)		0/4 (0%)
Hypotension	0/5 (0%)		1/3 (33.3%)		0/4 (0%)
Gastrointestinal disorders
Anorexia	0/5 (0%)		1/3 (33.3%)		0/4 (0%)
Dehydration	0/5 (0%)		1/3 (33.3%)		1/4 (25%)
Diarrhea	0/5 (0%)		2/3 (66.7%)		3/4 (75%)
Nausea	1/5 (20%)		2/3 (66.7%)		1/4 (25%)
Vomiting	1/5 (20%)		2/3 (66.7%)		2/4 (50%)
General disorders
Fatigue	3/5 (60%)		0/3 (0%)		0/4 (0%)
Hyperglycemia	3/5 (60%)		0/3 (0%)		1/4 (25%)
Hypoglycemia	1/5 (20%)		0/3 (0%)		0/4 (0%)
Back-pain	1/5 (20%)		0/3 (0%)		0/4 (0%)
Chest wall-pain	1/5 (20%)		0/3 (0%)		0/4 (0%)
Head/headache	1/5 (20%)		0/3 (0%)		0/4 (0%)
Hepatobiliary disorders
ALT- SGPT	2/5 (40%)		1/3 (33.3%)		1/4 (25%)
AST- SGOT	3/5 (60%)		2/3 (66.7%)		1/4 (25%)
Alkaline phosphatase	1/5 (20%)		0/3 (0%)		0/4 (0%)
Nervous system disorders
Syncope	0/5 (0%)		1/3 (33.3%)		0/4 (0%)
Renal and urinary disorders
Hyperuricemia	2/5 (40%)		2/3 (66.7%)		1/4 (25%)
Respiratory, thoracic and mediastinal disorders
Bicarbonate	0/5 (0%)		1/3 (33.3%)		0/4 (0%)
Cough	1/5 (20%)		0/3 (0%)		0/4 (0%)
Dyspnea	1/5 (20%)		0/3 (0%)		0/4 (0%)
Skin and subcutaneous tissue disorders
Rash	2/5 (40%)		0/3 (0%)		1/4 (25%)

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.