Acral Lentiginous Melanoma, Cutaneous Nodular Melanoma, Lentigo Maligna Melanoma, Low-CSD Melanoma, Mucosal Melanoma, Recurrent Melanoma, Stage IV Cutaneous Melanoma AJCC v6 and v7
Conditions
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.
Detailed description
PRIMARY OBJECTIVES: I. To assess the 1-year overall survival rate in patients with stage IV melanoma treated with dinaciclib. SECONDARY OBJECTIVES: I. 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. III. 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.
Interventions
DRUGDinaciclib
Given IV
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORChristopher D Lao
SWOG Cancer Research Network
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dinaciclib Patients receive dinaciclib IV over 2 hours on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. | 72 |
| Total | 72 |
Baseline characteristics
| Characteristic | Dinaciclib |
|---|---|
| Age, Continuous | 65.4 years |
| Elevated LDH No | 41 participants |
| Elevated LDH Yes | 31 participants |
| Hispanic No | 69 participants |
| Hispanic Unknown | 1 participants |
| Hispanic Yes | 2 participants |
| Performance Status 0 | 38 participants |
| Performance Status 1 | 34 participants |
| Primary Type Cutaneous | 55 participants |
| Primary Type Mucosal | 8 participants |
| Primary Type Unknown primary | 9 participants |
| Race/Ethnicity, Customized Asian | 2 participants |
| Race/Ethnicity, Customized Pacific Islander | 1 participants |
| Race/Ethnicity, Customized White | 69 participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 52 Participants |
| Site(s) of Metastases Bone | 18 participants |
| Site(s) of Metastases Brain | 0 participants |
| Site(s) of Metastases Liver | 23 participants |
| Site(s) of Metastases Lung | 41 participants |
| Site(s) of Metastases Lymph node, soft tissue, skin | 41 participants |
| Site(s) of Metastases Other non-visceral | 14 participants |
| Site(s) of Metastases Other visceral | 17 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| other Total, other adverse events | 64 / 72 |
| serious Total, serious adverse events | 30 / 72 |
Outcome results
Primary
Overall Survival
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dinaciclib | Overall Survival | 8 months |
Comparison: one-year overall survival estimate.95% CI: [0.27, 0.49]
Secondary
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs
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.
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dinaciclib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Edema: limb | 1 Participants |
| Dinaciclib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | SVT and nodal arrhythmia - Atrial fibrillation | 1 Participants |
| Dinaciclib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | AST, SGOT | 1 Participants |
| Dinaciclib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Cardiac troponin I (cTnI) | 1 Participants |
| Dinaciclib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Cardiac-ischemia/infarction | 1 Participants |
| Dinaciclib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Constitutional Symptoms-Other (Specify) | 1 Participants |
| Dinaciclib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dehydration | 1 Participants |
| Dinaciclib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Diarrhea | 11 Participants |
| Dinaciclib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dyspnea (shortness of breath) | 1 Participants |
| Dinaciclib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Fatigue (asthenia, lethargy, malaise) | 3 Participants |
| Dinaciclib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Febrile neutropenia | 2 Participants |
| Dinaciclib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypotension | 2 Participants |
| Dinaciclib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypoxia | 1 Participants |
| Dinaciclib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Leukocytes (total WBC) | 18 Participants |
| Dinaciclib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lymphopenia | 5 Participants |
| Dinaciclib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Metabolic/Laboratory-Other (Specify) | 2 Participants |
| Dinaciclib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Mucositis/stomatitis (clinical exam) - Oral cavity | 1 Participants |
| Dinaciclib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Muscle weakness, not d/t neuropathy - body/general | 1 Participants |
| Dinaciclib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Nausea | 1 Participants |
| Dinaciclib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Neutrophils/granulocytes (ANC/AGC) | 36 Participants |
| Dinaciclib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Ocular/Visual-Other (Specify) | 1 Participants |
| Dinaciclib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | PTT (Partial thromboplastin time) | 1 Participants |
| Dinaciclib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain - Abdomen NOS | 2 Participants |
| Dinaciclib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain - Back | 1 Participants |
| Dinaciclib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain - Cardiac/heart | 1 Participants |
| Dinaciclib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain - Extremity-limb | 1 Participants |
| Dinaciclib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain - Head/headache | 1 Participants |
| Dinaciclib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain - Tumor pain | 1 Participants |
| Dinaciclib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Prolonged QTc interval | 1 Participants |
| Dinaciclib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Renal failure | 1 Participants |
| Dinaciclib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | SVT and nodal arrhythmia - Atrial flutter | 1 Participants |
| Dinaciclib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | SVT and nodal arrhythmia - Sinus tachycardia | 1 Participants |
| Dinaciclib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Sodium, serum-low (hyponatremia) | 1 Participants |
| Dinaciclib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Somnolence/depressed level of consciousness | 1 Participants |
| Dinaciclib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Syncope (fainting) | 1 Participants |
| Dinaciclib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Thrombosis/thrombus/embolism | 1 Participants |
| Dinaciclib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Vascular-Other (Specify) | 1 Participants |
| Dinaciclib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Vision-blurred vision | 1 Participants |
| Dinaciclib | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Vomiting | 1 Participants |
Secondary
Progression-free Survival Assessed by Response Evaluation Criteria for Solid Tumors (RECIST)
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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dinaciclib | Progression-free Survival Assessed by Response Evaluation Criteria for Solid Tumors (RECIST) | 1.4 months |
Comparison: 6-month PFS estimate.95% CI: [0.03, 0.15]
Secondary
Response Rate (Confirmed and Unconfirmed Complete and Partial Responses) Assessed by RECIST
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
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Dinaciclib | Response Rate (Confirmed and Unconfirmed Complete and Partial Responses) Assessed by RECIST | 0 percentage of participants |