Trial Outcomes & Findings for Paclitaxel and Carboplatin or Temozolomide in Treating Patients With Stage IV Melanoma (NCT NCT00568451)

Results Overview

Response that was noted on 2 consecutive evaluations for at least 4 weeks apart. CR: Disappearance of all target lesions; PR: At least a 30 percent of decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. Target lesions: All measurable lesions up to a maximum of 10 lesions representative of all involved organs.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

12 participants

Primary outcome timeframe

Every other cycle of therapy (cycle=4 weeks) for the first 6 cycles of treatment

Results posted on

2015-12-30

Participant Flow

Twelve (12) participants with un-resectable stage IV malignant melanoma were enrolled in the study between June 2006 and November 2008 at Mayo Clinic Rochester.

One patient canceled participation in the trial prior to starting Temozolomide therapy. This patient was excluded from all analysis.

Participant milestones

Participant milestones
Measure	TMZ (Previously Treated) Previously chemotherapy treated cohorts: Temozolomide (TMZ)	TMZ (Chemo Naive) Chemotherapy-naive cohorts: Temozolomide (TMZ)
Overall Study STARTED	2	9
Overall Study COMPLETED	0	2
Overall Study NOT COMPLETED	2	7

Reasons for withdrawal

Reasons for withdrawal
Measure	PC (Previously Treated) Previously chemotherapy treated cohorts: Paclitaxel and Carboplatin (PC)	PC (Chemo Naive) Chemotherapy-naive cohorts: Paclitaxel and Carboplatin (PC)	TMZ (Previously Treated) Previously chemotherapy treated cohorts: Temozolomide (TMZ)	TMZ (Chemo Naive) Chemotherapy-naive cohorts: Temozolomide (TMZ)
Overall Study Disease Progression	0	0	2	7

Baseline Characteristics

Paclitaxel and Carboplatin or Temozolomide in Treating Patients With Stage IV Melanoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PC (Previously Treated) Previously chemotherapy treated cohorts: Paclitaxel and Carboplatin (PC)	PC (Chemo Naive) Chemotherapy-naive cohorts: Paclitaxel and Carboplatin (PC)	TMZ (Previously Treated) n=2 Participants Previously chemotherapy treated cohorts: Temozolomide (TMZ)	TMZ (Chemo Naive) n=9 Participants Chemotherapy-naive cohorts: Temozolomide (TMZ)	Total n=11 Participants Total of all reporting groups
Age, Continuous	—	—	61.5 years STANDARD_DEVIATION 14.85 • n=5 Participants	63.3 years STANDARD_DEVIATION 14.05 • n=4 Participants	62.4 years STANDARD_DEVIATION 12.97 • n=21 Participants
Gender Female	—	—	0 participants n=5 Participants	3 participants n=4 Participants	3 participants n=21 Participants
Gender Male	—	—	2 participants n=5 Participants	6 participants n=4 Participants	8 participants n=21 Participants
Region of Enrollment United States	—	—	2 participants n=5 Participants	9 participants n=4 Participants	11 participants n=21 Participants
M Stage M1a (skin/subcutaneous tissue/lymph node only)	—	—	0 participants n=5 Participants	1 participants n=4 Participants	1 participants n=21 Participants
M Stage M1b (lung)	—	—	1 participants n=5 Participants	3 participants n=4 Participants	4 participants n=21 Participants
M Stage M1c (other visceral sites)	—	—	1 participants n=5 Participants	5 participants n=4 Participants	6 participants n=21 Participants
Number of Metastatic Sites	—	—	2 Sites n=5 Participants	2 Sites n=4 Participants	2 Sites n=21 Participants

PRIMARY outcome

Timeframe: Every other cycle of therapy (cycle=4 weeks) for the first 6 cycles of treatment

Population: All subjects enrolled, met the eligibility criteria who have signed a consent form and have begun their study treatment were evaluable for response.

Response that was noted on 2 consecutive evaluations for at least 4 weeks apart. CR: Disappearance of all target lesions; PR: At least a 30 percent of decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. Target lesions: All measurable lesions up to a maximum of 10 lesions representative of all involved organs.

Outcome measures

Outcome measures
Measure	PC (Previously Treated) Previously chemotherapy treated cohorts: Paclitaxel and Carboplatin (PC)	PC (Chemo Naive) Chemotherapy-naive cohorts: Paclitaxel and Carboplatin (PC)	TMZ (Previously Treated) n=2 Participants Previously chemotherapy treated cohorts: Temozolomide (TMZ)	TMZ (Chemo Naive) n=9 Participants Chemotherapy-naive cohorts: Temozolomide (TMZ)
Number of Participants With an Objective Tumor Status of Either a Complete Response(CR) or Partial Response (PR), According to RECIST (Response Evaluation Criteria in Solid Tumors) Criteria	—	—	0 participants	2 participants

SECONDARY outcome

Timeframe: up to 2 years

Time to disease progression was defined as the time from registration to documentation of disease progression. Disease progression was measured according to the RECIST criteria. Progression: At least a 20 percent increase in the sum of of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Outcome measures

Outcome measures
Measure	PC (Previously Treated) n=11 Participants Previously chemotherapy treated cohorts: Paclitaxel and Carboplatin (PC)	PC (Chemo Naive) Chemotherapy-naive cohorts: Paclitaxel and Carboplatin (PC)	TMZ (Previously Treated) Previously chemotherapy treated cohorts: Temozolomide (TMZ)	TMZ (Chemo Naive) Chemotherapy-naive cohorts: Temozolomide (TMZ)
Time to Disease Progression	74 Days Interval 68.0 to 132.0	—	—	—

SECONDARY outcome

Timeframe: up to 2 years

Survival time was defined as the time from registration to death due to any cause.

Outcome measures

Outcome measures
Measure	PC (Previously Treated) n=11 Participants Previously chemotherapy treated cohorts: Paclitaxel and Carboplatin (PC)	PC (Chemo Naive) Chemotherapy-naive cohorts: Paclitaxel and Carboplatin (PC)	TMZ (Previously Treated) Previously chemotherapy treated cohorts: Temozolomide (TMZ)	TMZ (Chemo Naive) Chemotherapy-naive cohorts: Temozolomide (TMZ)
Survival Time	12.5 Months Interval 4.5 to There is not enough events reported to compute 95% CI upper limit.	—	—	—

SECONDARY outcome

Timeframe: up to 2 years

Population: Two complete tumor responses were documented. Both participants have since discontinued the study drug after 35 and 24 cycles respectively, and remain disease-free at 39 and 31.5 months since study entry. There is not enough participants to perform this analysis.

Duration of response was defined as the date at which the participant's objective status was first noted to be either a Complete Response or Partial Response to the date the progression was documented.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to 2 years

Population: There is not enough participants to perform this analysis.

Time series plot of the number of circulating cells will be constructed. The resulting plots will be visually inspected for trends within and between treatments. For each cell type, a point and an interval estimate of the number of participants (receiving a given treatment) who had at least a 2-fold increase in the number of circulating cells of that type will be constructed using the properties of the binomial distribution.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to 2 years

Population: There is not enough participants to perform this analysis.

For those patients who are HLA-A2+, the maximum post-treatment levels of MART-1, tyrosinase, and gp100 will be determined. For each of these specific melanoma specific antigens, the number of participants (within a given treatment) who gained or maintained immunity based on the maximum post-treatment level of that specific melanoma specific antigen will be determined.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to 2 years

Population: There is not enough participants to perform this analysis.

For each patient, a time series plot of the number of IFNγ producing peptide specific CTLs will be constructed. The resulting plots will be visually inspected for trends within and between treatments. A point and an interval estimate of the number of participants (receiving a given treatment) who had at least a 2-fold increase in the number of the number of IFNγ producing peptide specific CTLs will be constructed using the properties of the binomial distribution.

Outcome measures

Outcome data not reported

Adverse Events

TMZ (Previously Treated)

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

TMZ (Chemo Naive)

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

PC (Previously Treated)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

PC (Chemo Naive)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	TMZ (Previously Treated) n=2 participants at risk Previously chemotherapy treated cohorts: Temozolomide (TMZ)	TMZ (Chemo Naive) n=9 participants at risk Chemotherapy-naive cohorts: Temozolomide (TMZ)	PC (Previously Treated) Previously chemotherapy treated cohorts: Paclitaxel and Carboplatin (PC)	PC (Chemo Naive) Chemotherapy-naive cohorts: Paclitaxel and Carboplatin (PC)
Blood and lymphatic system disorders Anemia	0.00% 0/2	11.1% 1/9 • Number of events 1	— 0/0	— 0/0

Other adverse events

Other adverse events
Measure	TMZ (Previously Treated) n=2 participants at risk Previously chemotherapy treated cohorts: Temozolomide (TMZ)	TMZ (Chemo Naive) n=9 participants at risk Chemotherapy-naive cohorts: Temozolomide (TMZ)	PC (Previously Treated) Previously chemotherapy treated cohorts: Paclitaxel and Carboplatin (PC)	PC (Chemo Naive) Chemotherapy-naive cohorts: Paclitaxel and Carboplatin (PC)
Blood and lymphatic system disorders Anemia	50.0% 1/2 • Number of events 1	66.7% 6/9 • Number of events 29	— 0/0	— 0/0
General disorders Fatigue	0.00% 0/2	11.1% 1/9 • Number of events 1	— 0/0	— 0/0
Infections and infestations Bronchial infection	0.00% 0/2	11.1% 1/9 • Number of events 1	— 0/0	— 0/0
Infections and infestations Pneumonia	0.00% 0/2	11.1% 1/9 • Number of events 1	— 0/0	— 0/0
Investigations Leukopenia	0.00% 0/2	33.3% 3/9 • Number of events 6	— 0/0	— 0/0
Investigations Lymphopenia	0.00% 0/2	11.1% 1/9 • Number of events 13	— 0/0	— 0/0
Investigations Neutropenia	0.00% 0/2	22.2% 2/9 • Number of events 10	— 0/0	— 0/0
Investigations Platelet count decreased	50.0% 1/2 • Number of events 1	44.4% 4/9 • Number of events 8	— 0/0	— 0/0
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/2	11.1% 1/9 • Number of events 1	— 0/0	— 0/0

Additional Information

Svetomir N. Markovic M.D., Ph.D.

Mayo Clinic Cancer Center

Phone: 507-284-2511

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place