Malignant Melanoma
Conditions
Brief summary
This study will assess the preliminary anti-tumor activity and safety profile of a combination of bevacizumab and dacarbazine in participants with unresectable/metastatic melanoma not previously treated with chemotherapy for metastatic disease.
Interventions
DRUGBevacizumab
Bevacizumab will be given as 10 milligrams per kilogram (mg/kg) via intravenous (IV) infusion on Days 1 and 14 of each 28-day cycle.
DRUGDacarbazine
Dacarbazine will be given as 800 milligrams per square meter (mg/m\^2) via IV infusion on Day 1 of each 28-day cycle.
Sponsors
Hoffmann-La Roche
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
* Histologically or cytologically confirmed cutaneous malignant melanoma * Clinical evidence of metastatic disease and/or unresectable regional lymphatic disease and/or extensive in transit recurrent disease * Measurable and/or evaluable lesions according to RECIST
Exclusion criteria
* Prior interferon alfa and/or cytokine therapy for metastatic disease * Prior chemotherapy for metastatic disease * Brain metastases * Chronic daily treatment with high-dose aspirin (more than 325 milligrams per day) * Other co-existing malignancies or malignancies diagnosed within the past 5 years with the exception of basal cell cancer or cervical cancer in situ
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST) | Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months) | Tumor assessments were performed using RECIST. CR was defined as disappearance of all target and non-target lesions with normalization of tumor markers. PR was defined as greater than or equal to (≥) 30 percent (%) decrease in sum of longest diameter (LD) of target lesions in reference to sum of LD at Baseline. Both were to be confirmed at a follow-up visit at least 4 weeks from the initial assessment of CR or PR. The percentage of participants with a best overall response of CR or PR during the study was reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) With CR or PR According to RECIST | Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months) | Tumor assessments were performed using RECIST. DOR was defined as the time from first assessment of CR or PR to the time of death or disease progression, whichever occurred first. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to smallest sum on study or the appearance of new lesion(s). CR was defined as disappearance of all target and non-target lesions with normalization of tumor markers. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline. DOR was estimated by Kaplan-Meier methodology and expressed in months. |
| Percentage of Participants With Death or Disease Progression Following a Previous Assessment of CR, PR, or Stable Disease (SD) According to RECIST | Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months) | Tumor assessments were performed using RECIST. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to smallest sum on study or the appearance of new lesion(s). CR was defined as disappearance of all target and non-target lesions with normalization of tumor markers. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline. SD was defined as neither sufficient shrinkage to quality for PR nor sufficient increase to qualify for disease progression, using smallest sum of LD on study as reference. The percentage of participants who died or demonstrated disease progression among those with a previous assessment of CR, PR, or SD was reported. |
| DOR With CR, PR, or SD According to RECIST | Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months) | Tumor assessments were performed using RECIST. DOR was defined as the time from first assessment of CR, PR, or SD to the time of death or disease progression, whichever occurred first. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to smallest sum on study or the appearance of new lesion(s). CR was defined as disappearance of all target and non-target lesions with normalization of tumor markers. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline. SD was defined as neither sufficient shrinkage to quality for PR nor sufficient increase to qualify for disease progression, using smallest sum of LD on study as reference. DOR was estimated by Kaplan-Meier methodology and expressed in months. |
| Percentage of Participants With Death or Disease Progression According to RECIST | Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months) | Tumor assessments were performed using RECIST. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to smallest sum on study or the appearance of new lesion(s). The percentage of participants who died or demonstrated disease progression was reported. |
| Percentage of Participants With Death or Disease Progression Following a Previous Assessment of CR or PR According to RECIST | Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months) | Tumor assessments were performed using RECIST. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to smallest sum on study or the appearance of new lesion(s). CR was defined as disappearance of all target and non-target lesions with normalization of tumor markers. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline. The percentage of participants who died or demonstrated disease progression among those with a previous assessment of CR or PR was reported. |
| Percentage of Participants Who Discontinued Treatment | Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months) | The percentage of participants who discontinued treatment as a result of death, adverse event, disease progression, loss to follow-up, non-compliance, or consent withdrawal was reported. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to smallest sum on study or the appearance of new lesion(s). |
| Time to Treatment Failure (TTF) | Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months) | TTF was defined as the time from start of treatment to the time of treatment discontinuation as a result of death, adverse event, disease progression, loss to follow-up, non-compliance, or consent withdrawal was reported. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to smallest sum on study or the appearance of new lesion(s). TTF was estimated by Kaplan-Meier methodology and expressed in months. |
| Percentage of Participants Who Died | Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months) | The percentage of participants who died from any cause was reported. |
| Overall Survival (OS) | Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months) | OS was defined as the time from Baseline visit to the time of death from any cause. OS was estimated by Kaplan-Meier methodology and expressed in months. |
| Time to Progression (TTP) According to RECIST | Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months) | Tumor assessments were performed using RECIST. TTP was defined as the time from Baseline visit to time of death or disease progression, whichever occurred first. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to smallest sum on study or the appearance of new lesion(s). TTP was estimated by Kaplan-Meier methodology and expressed in months. |
Countries
Italy
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dacarbazine + Bevacizumab Participants with unresectable/metastatic melanoma not previously treated with chemotherapy for metastatic disease received dacarbazine as 800 mg/m\^2 via IV infusion on Day 1 and bevacizumab as 10 mg/kg via IV infusion on Days 1 and 14 of each 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, participant withdrawal, or physician decision to discontinue. | 37 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 5 |
| Overall Study | Medical Decision | 3 |
| Overall Study | Progression of Disease | 30 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Dacarbazine + Bevacizumab |
|---|---|
| Age, Continuous | 54.16 years STANDARD_DEVIATION 13.11 |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 32 / 37 |
| serious Total, serious adverse events | 5 / 37 |
Outcome results
Primary
Percentage of Participants With Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST)
Tumor assessments were performed using RECIST. CR was defined as disappearance of all target and non-target lesions with normalization of tumor markers. PR was defined as greater than or equal to (≥) 30 percent (%) decrease in sum of longest diameter (LD) of target lesions in reference to sum of LD at Baseline. Both were to be confirmed at a follow-up visit at least 4 weeks from the initial assessment of CR or PR. The percentage of participants with a best overall response of CR or PR during the study was reported.
Time frame: Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months)
Population: Intent-to-Treat (ITT) Population: All participants who signed the ICF, were assigned a study identifier, and received at least one dose of study medications.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dacarbazine + Bevacizumab | Percentage of Participants With Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST) | 18.92 percentage of participants |
Comparison: The observed percentage of participants with CR or PR was compared with the expected proportion under the null hypothesis (0.10) and analyzed for statistical significance using a one-sample exact binomial test.p-value: 0.071One-sample exact binomial test
Secondary
DOR With CR, PR, or SD According to RECIST
Tumor assessments were performed using RECIST. DOR was defined as the time from first assessment of CR, PR, or SD to the time of death or disease progression, whichever occurred first. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to smallest sum on study or the appearance of new lesion(s). CR was defined as disappearance of all target and non-target lesions with normalization of tumor markers. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline. SD was defined as neither sufficient shrinkage to quality for PR nor sufficient increase to qualify for disease progression, using smallest sum of LD on study as reference. DOR was estimated by Kaplan-Meier methodology and expressed in months.
Time frame: Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months)
Population: ITT Population. The Number of Participants Analyzed reflects the number of participants with a previous assessment of CR, PR, or SD.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dacarbazine + Bevacizumab | DOR With CR, PR, or SD According to RECIST | 12.52 months |
Secondary
Duration of Response (DOR) With CR or PR According to RECIST
Tumor assessments were performed using RECIST. DOR was defined as the time from first assessment of CR or PR to the time of death or disease progression, whichever occurred first. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to smallest sum on study or the appearance of new lesion(s). CR was defined as disappearance of all target and non-target lesions with normalization of tumor markers. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline. DOR was estimated by Kaplan-Meier methodology and expressed in months.
Time frame: Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months)
Population: ITT Population. The Number of Participants Analyzed reflects the number of participants with a previous assessment of CR or PR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dacarbazine + Bevacizumab | Duration of Response (DOR) With CR or PR According to RECIST | 16.89 months |
Secondary
Overall Survival (OS)
OS was defined as the time from Baseline visit to the time of death from any cause. OS was estimated by Kaplan-Meier methodology and expressed in months.
Time frame: Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months)
Population: ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dacarbazine + Bevacizumab | Overall Survival (OS) | 11.41 months |
Secondary
Percentage of Participants Who Died
The percentage of participants who died from any cause was reported.
Time frame: Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months)
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dacarbazine + Bevacizumab | Percentage of Participants Who Died | 81.08 percentage of participants |
Secondary
Percentage of Participants Who Discontinued Treatment
The percentage of participants who discontinued treatment as a result of death, adverse event, disease progression, loss to follow-up, non-compliance, or consent withdrawal was reported. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to smallest sum on study or the appearance of new lesion(s).
Time frame: Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months)
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dacarbazine + Bevacizumab | Percentage of Participants Who Discontinued Treatment | 91.89 percentage of participants |
Secondary
Percentage of Participants With Death or Disease Progression According to RECIST
Tumor assessments were performed using RECIST. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to smallest sum on study or the appearance of new lesion(s). The percentage of participants who died or demonstrated disease progression was reported.
Time frame: Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months)
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dacarbazine + Bevacizumab | Percentage of Participants With Death or Disease Progression According to RECIST | 81.08 percentage of participants |
Secondary
Percentage of Participants With Death or Disease Progression Following a Previous Assessment of CR or PR According to RECIST
Tumor assessments were performed using RECIST. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to smallest sum on study or the appearance of new lesion(s). CR was defined as disappearance of all target and non-target lesions with normalization of tumor markers. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline. The percentage of participants who died or demonstrated disease progression among those with a previous assessment of CR or PR was reported.
Time frame: Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months)
Population: ITT Population. The Number of Participants Analyzed reflects the number of participants with a previous assessment of CR or PR.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dacarbazine + Bevacizumab | Percentage of Participants With Death or Disease Progression Following a Previous Assessment of CR or PR According to RECIST | 57.14 percentage of participants |
Secondary
Percentage of Participants With Death or Disease Progression Following a Previous Assessment of CR, PR, or Stable Disease (SD) According to RECIST
Tumor assessments were performed using RECIST. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to smallest sum on study or the appearance of new lesion(s). CR was defined as disappearance of all target and non-target lesions with normalization of tumor markers. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline. SD was defined as neither sufficient shrinkage to quality for PR nor sufficient increase to qualify for disease progression, using smallest sum of LD on study as reference. The percentage of participants who died or demonstrated disease progression among those with a previous assessment of CR, PR, or SD was reported.
Time frame: Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months)
Population: ITT Population. The Number of Participants Analyzed reflects the number of participants with a previous assessment of CR, PR, or SD.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dacarbazine + Bevacizumab | Percentage of Participants With Death or Disease Progression Following a Previous Assessment of CR, PR, or Stable Disease (SD) According to RECIST | 72.22 percentage of participants |
Secondary
Time to Progression (TTP) According to RECIST
Tumor assessments were performed using RECIST. TTP was defined as the time from Baseline visit to time of death or disease progression, whichever occurred first. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to smallest sum on study or the appearance of new lesion(s). TTP was estimated by Kaplan-Meier methodology and expressed in months.
Time frame: Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months)
Population: ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dacarbazine + Bevacizumab | Time to Progression (TTP) According to RECIST | 5.48 months |
Secondary
Time to Treatment Failure (TTF)
TTF was defined as the time from start of treatment to the time of treatment discontinuation as a result of death, adverse event, disease progression, loss to follow-up, non-compliance, or consent withdrawal was reported. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to smallest sum on study or the appearance of new lesion(s). TTF was estimated by Kaplan-Meier methodology and expressed in months.
Time frame: Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months)
Population: ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dacarbazine + Bevacizumab | Time to Treatment Failure (TTF) | 3.05 months |