Trial Outcomes & Findings for Cabozantinib in Recurrent/Metastatic Merkel Cell Carcinoma (NCT NCT02036476)

NCT ID: NCT02036476

Last Updated: 2023-05-09

Results Overview

3-month DCR is the percentage of participants achieving complete response (CR), partial response (PR) or stable disease (SD) during first 3 months of treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PD is at least a 20% increase in sum LD of target lesions (smallest sum LD reference), new lesions, and/or unequivocal progression of existing non-target lesions. Stable disease (SD) is defined as any condition not meeting the above criteria and lasting at least 3 months from baseline.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

8 participants

Primary outcome timeframe

Disease was assessed on day 1 of weeks 3, 5, 7, 9, 11, 13 then every 4 weeks on treatment. Relative to this endpoint was observation up to 3 months on treatment. Length of longest follow up was 83 days.

Results posted on

2023-05-09

Participant Flow

Participants enrolled from February 2014 to March 2016.

Participant milestones

Participant milestones
Measure	Cabozantinib Cabozantinib 60 mg Oral Daily 28 days (4 weeks)
Overall Study STARTED	8
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Cabozantinib Cabozantinib 60 mg Oral Daily 28 days (4 weeks)
Overall Study Withdrawal by Subject	2
Overall Study Progressive Disease	4
Overall Study Unacceptable Toxicity	2

Baseline Characteristics

Cabozantinib in Recurrent/Metastatic Merkel Cell Carcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cabozantinib n=8 Participants Cabozantinib 60 mg Oral Daily 28 days (4 weeks)
Age, Continuous	64.9 years STANDARD_DEVIATION 12 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	2 Participants n=5 Participants
Race/Ethnicity, Customized White	6 Participants n=5 Participants

PRIMARY outcome

Timeframe: Disease was assessed on day 1 of weeks 3, 5, 7, 9, 11, 13 then every 4 weeks on treatment. Relative to this endpoint was observation up to 3 months on treatment. Length of longest follow up was 83 days.

Population: The analysis population is all enrolled participants.

Outcome measures

Outcome measures
Measure	Cabozantinib n=8 Participants Cabozantinib 60 mg given orally daily for 28 days (4 weeks) each cycle. Participants were treated until disease progression, unacceptable toxicity or withdrawal for other reasons.
3-Month Disease Control Rate (DCR)	12.5 percentage of participants Interval 0.64 to 47.07

SECONDARY outcome

Timeframe: Assessed every 2 weeks (w) from cycles 3-13 and then every 4w, day 30-37 post-treatment end and up to 8w in long-term follow-up. Length of longest follow up for the KM estimate was 126 days. Relative to this endpoint was 3-month probability.

Population: The analysis population is all enrolled participants.

3-month PFS is a probability based on the Kaplan-Meier (KM) method. PFS is defined as the duration of time from registration to documented disease progression (PD) or death, or censored at date of last disease assessment. Per RECIST v1.1: PD is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.

Outcome measures

Outcome measures
Measure	Cabozantinib n=8 Participants Cabozantinib 60 mg given orally daily for 28 days (4 weeks) each cycle. Participants were treated until disease progression, unacceptable toxicity or withdrawal for other reasons.
3-month Progression-free Survival (PFS)	0.19 probability Interval 0.046 to 0.81

SECONDARY outcome

Timeframe: 3 months

3-month OS rate is the percentage of patients alive at 3 months from registration.

Outcome measures

Outcome measures
Measure	Cabozantinib n=8 Participants Cabozantinib 60 mg given orally daily for 28 days (4 weeks) each cycle. Participants were treated until disease progression, unacceptable toxicity or withdrawal for other reasons.
3-Month Overall Survival (OS) Rate	100 percentage of participants Interval 65.0 to 100.0

SECONDARY outcome

Timeframe: Up to 126 days

Population: The analysis population is all treated participants.

All grade 3-5 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv4 as reported on case report forms were counted. Rate is the percentage of treated participants experiencing at least one treatment-related grade 3-5 AE of any type during the time of observation.

Outcome measures

Outcome measures
Measure	Cabozantinib n=8 Participants Cabozantinib 60 mg given orally daily for 28 days (4 weeks) each cycle. Participants were treated until disease progression, unacceptable toxicity or withdrawal for other reasons.
Grade 3-5 Treatment-Related Adverse Event (AE) Rate	0 percentage of participants Interval 0.0 to 31.0

Adverse Events

Cabozantinib

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Cabozantinib n=8 participants at risk Cabozantinib 60 mg Oral Daily 28 days (4 weeks)
Endocrine disorders Hypothyroidism	50.0% 4/8 • Assessed on treatment continuously on treatment up to 165 days. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Eye disorders Blurred vision	12.5% 1/8 • Assessed on treatment continuously on treatment up to 165 days. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Abdominal pain	12.5% 1/8 • Assessed on treatment continuously on treatment up to 165 days. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Cheilitis	12.5% 1/8 • Assessed on treatment continuously on treatment up to 165 days. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Constipation	62.5% 5/8 • Assessed on treatment continuously on treatment up to 165 days. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Diarrhea	25.0% 2/8 • Assessed on treatment continuously on treatment up to 165 days. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Gastroesophageal reflux disease	12.5% 1/8 • Assessed on treatment continuously on treatment up to 165 days. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Nausea	50.0% 4/8 • Assessed on treatment continuously on treatment up to 165 days. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Oral pain	37.5% 3/8 • Assessed on treatment continuously on treatment up to 165 days. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Vomiting	25.0% 2/8 • Assessed on treatment continuously on treatment up to 165 days. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
General disorders Fatigue	75.0% 6/8 • Assessed on treatment continuously on treatment up to 165 days. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
General disorders Pain	25.0% 2/8 • Assessed on treatment continuously on treatment up to 165 days. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
General disorders Non-cardiac chest pain	12.5% 1/8 • Assessed on treatment continuously on treatment up to 165 days. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Infections and infestations Penile infection	12.5% 1/8 • Assessed on treatment continuously on treatment up to 165 days. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Infections and infestations Skin infection	25.0% 2/8 • Assessed on treatment continuously on treatment up to 165 days. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations Weight loss	37.5% 3/8 • Assessed on treatment continuously on treatment up to 165 days. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Anorexia	87.5% 7/8 • Assessed on treatment continuously on treatment up to 165 days. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Dehydration	12.5% 1/8 • Assessed on treatment continuously on treatment up to 165 days. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hyponatremia	25.0% 2/8 • Assessed on treatment continuously on treatment up to 165 days. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hypophosphatemia	12.5% 1/8 • Assessed on treatment continuously on treatment up to 165 days. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Metabolism and nutrition disorders - Other	12.5% 1/8 • Assessed on treatment continuously on treatment up to 165 days. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Back pain	12.5% 1/8 • Assessed on treatment continuously on treatment up to 165 days. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Dizziness	25.0% 2/8 • Assessed on treatment continuously on treatment up to 165 days. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Dysgeusia	50.0% 4/8 • Assessed on treatment continuously on treatment up to 165 days. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Headache	12.5% 1/8 • Assessed on treatment continuously on treatment up to 165 days. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Psychiatric disorders Anxiety	12.5% 1/8 • Assessed on treatment continuously on treatment up to 165 days. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Renal and urinary disorders Proteinuria	12.5% 1/8 • Assessed on treatment continuously on treatment up to 165 days. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Renal and urinary disorders Renal and urinary disorders - Other	12.5% 1/8 • Assessed on treatment continuously on treatment up to 165 days. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Dyspnea	25.0% 2/8 • Assessed on treatment continuously on treatment up to 165 days. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Voice alteration	12.5% 1/8 • Assessed on treatment continuously on treatment up to 165 days. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Dry skin	25.0% 2/8 • Assessed on treatment continuously on treatment up to 165 days. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	25.0% 2/8 • Assessed on treatment continuously on treatment up to 165 days. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Skin/subcutaneous tissue disorders; Other	25.0% 2/8 • Assessed on treatment continuously on treatment up to 165 days. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Vascular disorders Hypertension	37.5% 3/8 • Assessed on treatment continuously on treatment up to 165 days. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.

Additional Information

Dr. Robert Haddad

Dana-Farber Cancer Institute

Phone: 617.632.3090

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place