Trial Outcomes & Findings for A Phase I/II Study of Dasatinib and Dacarbazine (NCT NCT00597038)

Last Updated: 2013-12-16

Results Overview

To determine the maximum tolerated dose of dasatinib twice a day when given with dacarbazine. Adverse events were graded using Common Terminology Criteria for Adverse Events version 3.0. Dose-limiting toxicities are defined as any grade 4 haematological toxicity (except asymptomatic grade 4 neutropenia for =/\< 7 days); prolonged grade 3 or 4 thrombocytopenia (47 days) or thrombocytopenia associated with bleeding, requiring platelet transfusion; any grade 3 or 4 nonhaematological toxicity despite optimal supportive care; any toxicity considered unacceptable by the study principal investigator.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

50 participants

Primary outcome timeframe

1 Year 3 Months

Results posted on

2013-12-16

Participant Flow

Eligible patients had unresectable stage III or stage IV melanoma. Patients were required to have measurable or evaluable disease and prior treatment with dacarbazine or temozolomide was not allowed.

Participant milestones

Participant milestones
Measure	Phase I Dose Escalation Dasatinib and Dacarbazine (DTIC). Dasatinib and Dacarbazine (DTIC). The first cohort was a dasatinib dose of 50 mg by mouth (PO) twice a day (BID) given days 2-19 with DTIC given at a dose of 800 mg/m2 once every 3 weeks. The dose escalation was continued until MTD and a recommended Phase II dose was established.	Phase II Dose Treatment Dasatinib and Dacarbazine (DTIC). Dasatinib and Dacarbazine (DTIC). The recommended phase II dose was dasatinib 70 mg BID with dacarbazine 800 mgm\^2.
Overall Study STARTED	16	34
Overall Study COMPLETED	14	30
Overall Study NOT COMPLETED	2	4

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Phase I/II Study of Dasatinib and Dacarbazine

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase I Dose Escalation n=16 Participants Dasatinib and Dacarbazine (DTIC). Dasatinib and Dacarbazine (DTIC). The first cohort was a dasatinib dose of 50 mg by mouth (PO) twice a day (BID) given days 2-19 with DTIC given at a dose of 800 mg/m2 once every 3 weeks. The dose escalation was continued until MTD and a recommended Phase II dose was established.	Phase II Dose Treatment n=34 Participants Dasatinib and Dacarbazine (DTIC). Dasatinib and Dacarbazine (DTIC). The recommended phase II dose was dasatinib 70 mg BID with dacarbazine 800 mgm\^2.	Total n=50 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=5 Participants	20 Participants n=7 Participants	26 Participants n=5 Participants
Age, Categorical >=65 years	10 Participants n=5 Participants	14 Participants n=7 Participants	24 Participants n=5 Participants
Age, Continuous	68.1 years n=5 Participants	60.3 years n=7 Participants	62.3 years n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	13 Participants n=7 Participants	19 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	21 Participants n=7 Participants	31 Participants n=5 Participants
Region of Enrollment United States	16 participants n=5 Participants	34 participants n=7 Participants	50 participants n=5 Participants

PRIMARY outcome

Timeframe: 1 Year 3 Months

Population: All participants in Arm A

Outcome measures

Outcome measures
Measure	Phase I Dose Escalation n=16 Participants Dasatinib and Dacarbazine (DTIC)	Phase II Dose Treatment Dasatinib and Dacarbazine (DTIC). Dasatinib and Dacarbazine (DTIC). The recommended phase II dose was dasatinib 70 mg BID with dacarbazine 800 mgm\^2.
Recommended Phase II Dose Recommended Dasatinib Dose mg	70 mg	—
Recommended Phase II Dose Recommended Dacarbazine Dose mg/m^2	800 mg	—

PRIMARY outcome

Timeframe: 1 Year 6 Months

Population: Patients receiving dasatinib at 70 mg PO BID

Phase II - To determine the overall response rate (ORR) of the combination of dasatinib and DTIC by the Response Evaluation Criteria in Solid Tumors (RECIST v1.0). Tumor assessments were made at baseline and at the end of every second cycle (i.e. every 6 weeks). Partial and complete responses were defined by the best treatment response achieved.

Outcome measures

Outcome measures
Measure	Phase I Dose Escalation n=29 Participants Dasatinib and Dacarbazine (DTIC)	Phase II Dose Treatment Dasatinib and Dacarbazine (DTIC). Dasatinib and Dacarbazine (DTIC). The recommended phase II dose was dasatinib 70 mg BID with dacarbazine 800 mgm\^2.
Phase II - Number of Participants With Overall Response (OR)	4 participants	—

SECONDARY outcome

Timeframe: 6 Months

Population: Patients receiving dasatinib at 70 mg PO BID

Phase II - PFS Rate in patients receiving dasatinib 70 mg orally (PO) twice a day (BID). Tumor assessments were made at baseline and at the end of every second cycle (i.e. every 6 weeks). Partial and complete responses were defined by the best treatment response achieved. Stable disease was defined as maintenance of the sum of lesions diameters between a 30% reduction and a 20% increase of overall tumour size over 12 weeks or longer.

Outcome measures

Outcome measures
Measure	Phase I Dose Escalation n=29 Participants Dasatinib and Dacarbazine (DTIC)	Phase II Dose Treatment Dasatinib and Dacarbazine (DTIC). Dasatinib and Dacarbazine (DTIC). The recommended phase II dose was dasatinib 70 mg BID with dacarbazine 800 mgm\^2.
Number of Participants With Progression Free Survival (PFS) at 6 Months	6 participants	—

SECONDARY outcome

Timeframe: 12 Months

Population: All participants

Phase II - To determine Overall Survival of patients treated with the combination of dasatinib and DTIC at 12 months.

Outcome measures

Outcome measures
Measure	Phase I Dose Escalation n=16 Participants Dasatinib and Dacarbazine (DTIC)	Phase II Dose Treatment n=34 Participants Dasatinib and Dacarbazine (DTIC). Dasatinib and Dacarbazine (DTIC). The recommended phase II dose was dasatinib 70 mg BID with dacarbazine 800 mgm\^2.
Number of Participants With 12 Month Overall Survival (OS)	9 participants	8 participants

Adverse Events

Phase I Dose Escalation

Serious events: 9 serious events

Other events: 4 other events

Deaths: 0 deaths

Phase II Dose Treatment

Serious events: 11 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Phase I Dose Escalation n=16 participants at risk Dasatinib and Dacarbazine (DTIC). Dasatinib and Dacarbazine (DTIC). The first cohort was a dasatinib dose of 50 mg by mouth (PO) twice a day (BID) given days 2-19 with DTIC given at a dose of 800 mg/m2 once every 3 weeks. The dose escalation was continued until MTD and a recommended Phase II dose was established.	Phase II Dose Treatment n=34 participants at risk Dasatinib and Dacarbazine (DTIC). Dasatinib and Dacarbazine (DTIC). The recommended phase II dose was dasatinib 70 mg BID with dacarbazine 800 mgm\^2.
General disorders Allergic reaction/hypersensitivity - Grade 2	6.2% 1/16 • Number of events 1 • First on treatment date to last off study date: 2 years, 4 months.	0.00% 0/34 • First on treatment date to last off study date: 2 years, 4 months.
Blood and lymphatic system disorders Hemoglobin - Grade 2	0.00% 0/16 • First on treatment date to last off study date: 2 years, 4 months.	2.9% 1/34 • Number of events 1 • First on treatment date to last off study date: 2 years, 4 months.
Gastrointestinal disorders Ascites (non-malignant) - Grade 2	0.00% 0/16 • First on treatment date to last off study date: 2 years, 4 months.	2.9% 1/34 • Number of events 1 • First on treatment date to last off study date: 2 years, 4 months.
Gastrointestinal disorders Diarrhea - Grade 2	0.00% 0/16 • First on treatment date to last off study date: 2 years, 4 months.	5.9% 2/34 • Number of events 2 • First on treatment date to last off study date: 2 years, 4 months.
Infections and infestations Infection - Grade 2	6.2% 1/16 • Number of events 1 • First on treatment date to last off study date: 2 years, 4 months.	0.00% 0/34 • First on treatment date to last off study date: 2 years, 4 months.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils - Skin - Grade 2	6.2% 1/16 • Number of events 1 • First on treatment date to last off study date: 2 years, 4 months.	0.00% 0/34 • First on treatment date to last off study date: 2 years, 4 months.
General disorders Pain - Chest wall - Grade 2	6.2% 1/16 • Number of events 1 • First on treatment date to last off study date: 2 years, 4 months.	0.00% 0/34 • First on treatment date to last off study date: 2 years, 4 months.
Respiratory, thoracic and mediastinal disorders Pleural effusion (non-malignant) - Grade 2	0.00% 0/16 • First on treatment date to last off study date: 2 years, 4 months.	2.9% 1/34 • Number of events 1 • First on treatment date to last off study date: 2 years, 4 months.

Additional Information

Adil Daud, Director, Melanoma Clinical Research

UCSF Helen Diller Family Comprehensive Cancer Center

Phone: 415-353-7392

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Phase I Dose Escalation n=16 participants at risk Dasatinib and Dacarbazine (DTIC). Dasatinib and Dacarbazine (DTIC). The first cohort was a dasatinib dose of 50 mg by mouth (PO) twice a day (BID) given days 2-19 with DTIC given at a dose of 800 mg/m2 once every 3 weeks. The dose escalation was continued until MTD and a recommended Phase II dose was established.	Phase II Dose Treatment n=34 participants at risk Dasatinib and Dacarbazine (DTIC). Dasatinib and Dacarbazine (DTIC). The recommended phase II dose was dasatinib 70 mg BID with dacarbazine 800 mgm\^2.
Blood and lymphatic system disorders Blood/Bone Marrow - Grade 3	0.00% 0/16 • First on treatment date to last off study date: 2 years, 4 months.	2.9% 1/34 • Number of events 1 • First on treatment date to last off study date: 2 years, 4 months.
Blood and lymphatic system disorders Hemoglobin - Grade 4	12.5% 2/16 • Number of events 3 • First on treatment date to last off study date: 2 years, 4 months.	0.00% 0/34 • First on treatment date to last off study date: 2 years, 4 months.
Blood and lymphatic system disorders Neutrophils/granulocytes - Grade 4	6.2% 1/16 • Number of events 1 • First on treatment date to last off study date: 2 years, 4 months.	0.00% 0/34 • First on treatment date to last off study date: 2 years, 4 months.
Blood and lymphatic system disorders Platelets - Grade 3	6.2% 1/16 • Number of events 1 • First on treatment date to last off study date: 2 years, 4 months.	0.00% 0/34 • First on treatment date to last off study date: 2 years, 4 months.
Blood and lymphatic system disorders Platelets - Grade 4	0.00% 0/16 • First on treatment date to last off study date: 2 years, 4 months.	2.9% 1/34 • Number of events 1 • First on treatment date to last off study date: 2 years, 4 months.
Cardiac disorders Cardiac general - Grade 3	0.00% 0/16 • First on treatment date to last off study date: 2 years, 4 months.	2.9% 1/34 • Number of events 1 • First on treatment date to last off study date: 2 years, 4 months.
Cardiac disorders Cardiac ischemia/infarction	0.00% 0/16 • First on treatment date to last off study date: 2 years, 4 months.	2.9% 1/34 • Number of events 1 • First on treatment date to last off study date: 2 years, 4 months.
General disorders Death not associated with CTCAE term - Disease progression not otherwise specified (NOS) - Grade 5	6.2% 1/16 • Number of events 1 • First on treatment date to last off study date: 2 years, 4 months.	5.9% 2/34 • Number of events 2 • First on treatment date to last off study date: 2 years, 4 months.
Gastrointestinal disorders Diarrhea - Grade 3	0.00% 0/16 • First on treatment date to last off study date: 2 years, 4 months.	2.9% 1/34 • Number of events 1 • First on treatment date to last off study date: 2 years, 4 months.
General disorders Hemorrhage, GI - Lower GI NOS - Grade 3	0.00% 0/16 • First on treatment date to last off study date: 2 years, 4 months.	2.9% 1/34 • Number of events 1 • First on treatment date to last off study date: 2 years, 4 months.
General disorders Hemorrhage, GI - Lower GI NOS - Grade 4	6.2% 1/16 • Number of events 1 • First on treatment date to last off study date: 2 years, 4 months.	0.00% 0/34 • First on treatment date to last off study date: 2 years, 4 months.
Infections and infestations Febrile neutropenia - Grade 3	12.5% 2/16 • Number of events 2 • First on treatment date to last off study date: 2 years, 4 months.	2.9% 1/34 • Number of events 1 • First on treatment date to last off study date: 2 years, 4 months.
Infections and infestations Infection with Grade 3 or 4 neutrophils - skin - Grade 3	6.2% 1/16 • Number of events 1 • First on treatment date to last off study date: 2 years, 4 months.	0.00% 0/34 • First on treatment date to last off study date: 2 years, 4 months.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils - skin - Grade 3	6.2% 1/16 • Number of events 1 • First on treatment date to last off study date: 2 years, 4 months.	0.00% 0/34 • First on treatment date to last off study date: 2 years, 4 months.
Infections and infestations Infection with unknown ANC - Joint - Grade 3	6.2% 1/16 • Number of events 1 • First on treatment date to last off study date: 2 years, 4 months.	0.00% 0/34 • First on treatment date to last off study date: 2 years, 4 months.
Blood and lymphatic system disorders Edema - limb - Grade 3	0.00% 0/16 • First on treatment date to last off study date: 2 years, 4 months.	2.9% 1/34 • Number of events 1 • First on treatment date to last off study date: 2 years, 4 months.
Psychiatric disorders Mental status - Grade 4	0.00% 0/16 • First on treatment date to last off study date: 2 years, 4 months.	2.9% 1/34 • Number of events 1 • First on treatment date to last off study date: 2 years, 4 months.
General disorders Pain - Abdomen NOS - Grade 3	0.00% 0/16 • First on treatment date to last off study date: 2 years, 4 months.	2.9% 1/34 • Number of events 1 • First on treatment date to last off study date: 2 years, 4 months.
General disorders Pain - Abdomen NOS - Grade 4	6.2% 1/16 • Number of events 1 • First on treatment date to last off study date: 2 years, 4 months.	0.00% 0/34 • First on treatment date to last off study date: 2 years, 4 months.
Respiratory, thoracic and mediastinal disorders Dyspnea - Grade 3	0.00% 0/16 • First on treatment date to last off study date: 2 years, 4 months.	5.9% 2/34 • Number of events 3 • First on treatment date to last off study date: 2 years, 4 months.
Respiratory, thoracic and mediastinal disorders Dyspnea - Grade 5	0.00% 0/16 • First on treatment date to last off study date: 2 years, 4 months.	2.9% 1/34 • Number of events 1 • First on treatment date to last off study date: 2 years, 4 months.