Trial Outcomes & Findings for Individualized Temozolomide in Treating Patients With Stage IV Melanoma That Cannot Be Removed By Surgery (NCT NCT01328535)

Last Updated: 2020-10-22

Results Overview

The distribution of time to progression will be estimated using the method of Kaplan-Meier and the 4 month progression-free rate (percentage) will be provided. Progression is defined as: At least one of the following must be true: At least one new malignant lesion, which also includes any lymph node that was normal at baseline (\< 1.0 cm short axis) and increased to ≥ 1.0 cm short axis during follow-up. At least a 20% increase in PBSD (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking as reference the MSD. In addition, the PBSD must also demonstrate an absolute increase of at least 0.5 cm from the MSD.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

25 participants

Primary outcome timeframe

Time from registration to the earliest date of documentation of disease progression, assessed at 4 months

Results posted on

2020-10-22

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment (Individualized Chemotherapy) Patients with an established biorhythm receive TMZ PO on recommended day for 5 days. Treatment repeats every 21-42 days until disease progression or unacceptable toxicity. Patients without an established biorhythm receive TMZ PO on days 1-5. Courses repeat every 28 days until disease progression or unacceptable toxicity.
Overall Study STARTED	25
Overall Study COMPLETED	24
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment (Individualized Chemotherapy) Patients with an established biorhythm receive TMZ PO on recommended day for 5 days. Treatment repeats every 21-42 days until disease progression or unacceptable toxicity. Patients without an established biorhythm receive TMZ PO on days 1-5. Courses repeat every 28 days until disease progression or unacceptable toxicity.
Overall Study Ineligible	1

Baseline Characteristics

Individualized Temozolomide in Treating Patients With Stage IV Melanoma That Cannot Be Removed By Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Individualized Chemotherapy) n=24 Participants Patients with an established biorhythm receive TMZ PO on recommended day for 5 days. Treatment repeats every 21-42 days until disease progression or unacceptable toxicity. Patients without an established biorhythm receive TMZ PO on days 1-5. Courses repeat every 28 days until disease progression or unacceptable toxicity.
Age, Continuous	69.5 years n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants
Region of Enrollment United States	24 Participants n=5 Participants

PRIMARY outcome

Timeframe: Time from registration to the earliest date of documentation of disease progression, assessed at 4 months

Population: Only patients who were evaluable for the primary endpoint were included in the analysis.

Outcome measures

Outcome measures
Measure	Treatment (Timed Individualized Chemotherapy) n=18 Participants Patients with an established biorhythm receive timed TMZ PO on recommended day for 5 days. Treatment repeats every 21-42 days until disease progression or unacceptable toxicity. Patients without an established biorhythm receive TMZ PO on days 1-5. Courses repeat every 28 days until disease progression or unacceptable toxicity.	Treatment (Untimed Individualized Chemotherapy) Patients with an established biorhythm receive untimed TMZ PO on recommended day for 5 days. Treatment repeats every 21-42 days until disease progression or unacceptable toxicity. Patients without an established biorhythm receive TMZ PO on days 1-5. Courses repeat every 28 days until disease progression or unacceptable toxicity.
Progression-Free Survival at 4 Months	22.2 percentage of patients Interval 6.4 to 47.6	—

SECONDARY outcome

Timeframe: Up to 2 years

Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined as:At least one of the following must be true: At least one new malignant lesion, which also includes any lymph node that was normal at baseline (\< 1.0 cm short axis) and increased to ≥ 1.0 cm short axis during follow-up. At least a 20% increase in PBSD (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking as reference the MSD (Section 11.41). In addition, the PBSD must also demonstrate an absolute increase of at least 0.5 cm from the MSD. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.

Outcome measures

Outcome measures
Measure	Treatment (Timed Individualized Chemotherapy) n=18 Participants Patients with an established biorhythm receive timed TMZ PO on recommended day for 5 days. Treatment repeats every 21-42 days until disease progression or unacceptable toxicity. Patients without an established biorhythm receive TMZ PO on days 1-5. Courses repeat every 28 days until disease progression or unacceptable toxicity.	Treatment (Untimed Individualized Chemotherapy) n=6 Participants Patients with an established biorhythm receive untimed TMZ PO on recommended day for 5 days. Treatment repeats every 21-42 days until disease progression or unacceptable toxicity. Patients without an established biorhythm receive TMZ PO on days 1-5. Courses repeat every 28 days until disease progression or unacceptable toxicity.
Progression-Free Survival	3.4 months Interval 2.7 to 9.9	7.2 months Interval 2.5 to The 95% confidence interval upper bound was not reached.

SECONDARY outcome

Timeframe: Up to 2 years

Overall survival time is defined as the time from randomization to death due to any cause. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.

Outcome measures

Outcome measures
Measure	Treatment (Timed Individualized Chemotherapy) n=18 Participants Patients with an established biorhythm receive timed TMZ PO on recommended day for 5 days. Treatment repeats every 21-42 days until disease progression or unacceptable toxicity. Patients without an established biorhythm receive TMZ PO on days 1-5. Courses repeat every 28 days until disease progression or unacceptable toxicity.	Treatment (Untimed Individualized Chemotherapy) n=6 Participants Patients with an established biorhythm receive untimed TMZ PO on recommended day for 5 days. Treatment repeats every 21-42 days until disease progression or unacceptable toxicity. Patients without an established biorhythm receive TMZ PO on days 1-5. Courses repeat every 28 days until disease progression or unacceptable toxicity.
Overall Survival	23.1 months Interval 12.2 to The 95% confidence interval upper bound was not reached.	17.5 months Interval 12.2 to The 95% confidence interval upper bound was not reached.

SECONDARY outcome

Timeframe: Up to 2 years

The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns within patient groups. In addition, we will review all adverse event data that is graded as 3, 4, or 5 and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing. The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below.

Outcome measures

Outcome measures
Measure	Treatment (Timed Individualized Chemotherapy) n=24 Participants Patients with an established biorhythm receive timed TMZ PO on recommended day for 5 days. Treatment repeats every 21-42 days until disease progression or unacceptable toxicity. Patients without an established biorhythm receive TMZ PO on days 1-5. Courses repeat every 28 days until disease progression or unacceptable toxicity.	Treatment (Untimed Individualized Chemotherapy) Patients with an established biorhythm receive untimed TMZ PO on recommended day for 5 days. Treatment repeats every 21-42 days until disease progression or unacceptable toxicity. Patients without an established biorhythm receive TMZ PO on days 1-5. Courses repeat every 28 days until disease progression or unacceptable toxicity.
Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4) White Blood Cell Decreased	8.3 percentage of patients	—
Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4) Fatigue	4.2 percentage of patients	—
Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4) Febrile Neutropenia	8.3 percentage of patients	—
Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4) Neutrophil Count Decreased	8.3 percentage of patients	—
Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4) Platelet Count Decreased	25 percentage of patients	—
Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4) Sepsis	4.2 percentage of patients	—
Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4) Urinary Tract Infection	4.2 percentage of patients	—
Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4) Abdominal Infection	4.2 percentage of patients	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 6 months

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 2 years

Outcome measures

Outcome data not reported

Adverse Events

Treatment (Individualized Chemotherapy)

Serious events: 3 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (Individualized Chemotherapy) n=24 participants at risk Patients with an established biorhythm receive TMZ PO on recommended day for 5 days. Treatment repeats every 21-42 days until disease progression or unacceptable toxicity. Patients without an established biorhythm receive TMZ PO on days 1-5. Courses repeat every 28 days until disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Anemia	4.2% 1/24 • Number of events 1 • Up to 2 years The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
Blood and lymphatic system disorders Febrile neutropenia	4.2% 1/24 • Number of events 1 • Up to 2 years The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
Gastrointestinal disorders Abdominal pain	4.2% 1/24 • Number of events 1 • Up to 2 years The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
Gastrointestinal disorders Constipation	4.2% 1/24 • Number of events 1 • Up to 2 years The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
General disorders Fatigue	4.2% 1/24 • Number of events 1 • Up to 2 years The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
Infections and infestations Abdominal infection	4.2% 1/24 • Number of events 1 • Up to 2 years The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
Infections and infestations Sepsis	4.2% 1/24 • Number of events 1 • Up to 2 years The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
Investigations Neutrophil count decreased	4.2% 1/24 • Number of events 1 • Up to 2 years The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
Investigations Platelet count decreased	4.2% 1/24 • Number of events 1 • Up to 2 years The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
Investigations White blood cell decreased	4.2% 1/24 • Number of events 1 • Up to 2 years The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).

Other adverse events

Other adverse events
Measure	Treatment (Individualized Chemotherapy) n=24 participants at risk Patients with an established biorhythm receive TMZ PO on recommended day for 5 days. Treatment repeats every 21-42 days until disease progression or unacceptable toxicity. Patients without an established biorhythm receive TMZ PO on days 1-5. Courses repeat every 28 days until disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Anemia	58.3% 14/24 • Number of events 55 • Up to 2 years The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other, specify	4.2% 1/24 • Number of events 1 • Up to 2 years The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
Blood and lymphatic system disorders Febrile neutropenia	4.2% 1/24 • Number of events 1 • Up to 2 years The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
Gastrointestinal disorders Abdominal pain	4.2% 1/24 • Number of events 1 • Up to 2 years The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
Gastrointestinal disorders Constipation	12.5% 3/24 • Number of events 5 • Up to 2 years The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
Gastrointestinal disorders Hemorrhoidal hemorrhage	4.2% 1/24 • Number of events 1 • Up to 2 years The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
Gastrointestinal disorders Nausea	8.3% 2/24 • Number of events 2 • Up to 2 years The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
Gastrointestinal disorders Vomiting	4.2% 1/24 • Number of events 1 • Up to 2 years The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
General disorders Chills	4.2% 1/24 • Number of events 1 • Up to 2 years The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
General disorders Fatigue	20.8% 5/24 • Number of events 6 • Up to 2 years The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
Infections and infestations Soft tissue infection	8.3% 2/24 • Number of events 4 • Up to 2 years The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
Infections and infestations Urinary tract infection	4.2% 1/24 • Number of events 1 • Up to 2 years The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
Investigations Aspartate aminotransferase increased	4.2% 1/24 • Number of events 1 • Up to 2 years The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
Investigations Neutrophil count decreased	29.2% 7/24 • Number of events 9 • Up to 2 years The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
Investigations Platelet count decreased	70.8% 17/24 • Number of events 52 • Up to 2 years The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
Investigations White blood cell decreased	33.3% 8/24 • Number of events 10 • Up to 2 years The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
Metabolism and nutrition disorders Anorexia	8.3% 2/24 • Number of events 2 • Up to 2 years The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	4.2% 1/24 • Number of events 2 • Up to 2 years The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
Vascular disorders Hypertension	4.2% 1/24 • Number of events 2 • Up to 2 years The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).

Additional Information

Roxana S. Dronca, M.D.

Mayo Clinic

Phone: 507/284-2511

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place