Trial Outcomes & Findings for Ziv-Aflibercept for Advanced Progressive Carcinoid Tumors (NCT NCT01782443)

Last Updated: 2023-08-14

Results Overview

To evaluate the progression-free survival (PFS) duration of patients with metastatic, unresectable, progressive carcinoid tumors treated with Ziv-aflibercept. Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) was used. Progressive Disease (PD) is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study with at least a 5 mm absolute increase in the sum of all lesions. The appearance of one or more new lesions denotes disease progression. Partial Response (PR) is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

19 participants

Primary outcome timeframe

2 years

Results posted on

2023-08-14

Participant Flow

Participant milestones

Participant milestones
Measure	Experimental Treatment Arm (Ziv-aflibercept) Ziv-aflibercept IV every 2 weeks, 4 mg/kg for the first 10 patients, 2 mg/kg for the remaining 9 patients
Overall Study STARTED	19
Overall Study COMPLETED	19
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Ziv-Aflibercept for Advanced Progressive Carcinoid Tumors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Experimental Treatment Arm (Ziv-aflibercept) n=19 Participants Ziv-aflibercept IV every 2 weeks, 4 mg/kg for the first 10 patients, 2 mg/kg for the remaining 9 patients
Age, Continuous	61 years n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants
Race (NIH/OMB) White	17 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	19 participants n=5 Participants
primary site midgut	12 Participants n=5 Participants
primary site unknown	4 Participants n=5 Participants
primary site rectum	1 Participants n=5 Participants
primary site lung	1 Participants n=5 Participants
primary site thymus	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: 2 years

Population: The efficacy of ziv-aflibercept was evaluated amongst all patients who were treated on protocol (4 mg/kg in 10 patients, reduced to 2 mg/kg in 9 patients due to adverse events observed at the higher does level).

Outcome measures

Outcome measures
Measure	Experimental Treatment Arm (Ziv-aflibercept) n=19 Participants Ziv-aflibercept IV every 2 weeks, 4 mg/kg for the first 10 patients, 2 mg/kg for the remaining 9 patients
Progression Free Survival	11.8 months Interval 3.2 to 16.1

SECONDARY outcome

Timeframe: 2 years

Population: 14 patients were evaluated for disease response per RECIST 1.1. The remaining 5 patients were not evaluable for response by RECIST 1.1 because they did not undergo protocol restaging due to early withdrawal from the study prior to reaching first protocol restaging.

To evaluate disease response using RECIST criteria, version 1.1, of patients with advanced carcinoid tumors treated with Ziv-aflibercept. Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI or CT include the following categories of disease response: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable disease (SD), less than 30% decrease but no more than 20% increase in sum of the longest diameter of target lesions.

Outcome measures

Outcome measures
Measure	Experimental Treatment Arm (Ziv-aflibercept) n=14 Participants Ziv-aflibercept IV every 2 weeks, 4 mg/kg for the first 10 patients, 2 mg/kg for the remaining 9 patients
Evaluation of Disease Response Partial Response	1 Participants
Evaluation of Disease Response Stable Disease	13 Participants

SECONDARY outcome

Timeframe: 2 years

Population: 12 participants were evaluable based on baseline assessment of serum chromogranin A. These patients were evaluated for a greater than 50% drop in chromogranin A from baseline while on treatment.

To evaluate biochemical response in patients with elevated chromogranin A at baseline, using levels of chromogranin-A measured at baseline and following treatment with Ziv-aflibercept. Biochemical response was defined as greater than 50% drop in chromogranin A from baseline. During the screening period, all patients were evaluated for serum chromogranin A. Per protocol, if results of these are normal at baseline, they were not repeated while on study. If above institutional ULN at baseline, they were evaluated at time of tumor restaging.

Outcome measures

Outcome measures
Measure	Experimental Treatment Arm (Ziv-aflibercept) n=12 Participants Ziv-aflibercept IV every 2 weeks, 4 mg/kg for the first 10 patients, 2 mg/kg for the remaining 9 patients
Evaluation of Biochemical Response - Number of Patients With Greater Than 50% Drop in Chromogranin A From Baseline	2 Participants

SECONDARY outcome

Timeframe: 2 years

Population: 11 patients were evaluable based on baseline assessment of 24hr urine 5-HIAA. These patients were followed for greater than 50% drop in 24hr urine 5-HIAA after starting treatment.

To evaluate biochemical response in patients with elevated 24hr urine 5-HIAA at baseline, using levels of 24hr urine 5-HIAA at baseline and following treatment with Ziv-aflibercept. Biochemical response was defined as greater than 50% drop in 24hr urine 5-HIAA from baseline. During the screening period, all patients were evaluated for 24hr urine 5HIAA. Per protocol, if results of these were normal at baseline, they were not repeated while on study. If above institutional ULN at baseline, they were evaluated at time of tumor restaging.

Outcome measures

Outcome measures
Measure	Experimental Treatment Arm (Ziv-aflibercept) n=11 Participants Ziv-aflibercept IV every 2 weeks, 4 mg/kg for the first 10 patients, 2 mg/kg for the remaining 9 patients
Biochemical Response - Number of Patients With Greater Than 50% Drop in 24hr Urine 5-HIAA From Baseline	1 Participants

Adverse Events

Ziv-aflibercept 4mg/kg

Serious events: 5 serious events

Other events: 10 other events

Deaths: 1 deaths

Ziv-aflibercept 2mg/kg

Serious events: 5 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Ziv-aflibercept 4mg/kg n=10 participants at risk Patients treated with a starting dose of Ziv-aflibercept 4 mg/kg	Ziv-aflibercept 2mg/kg n=9 participants at risk Patients treated with a starting dose of Ziv-aflibercept 2 mg/kg
Cardiac disorders Hypertension	20.0% 2/10 • Patients were followed for AEs from first dose of study treatment, throughout the study, and through 30 days of the last study treatment, an average of 16 months. Participants removed from study for unacceptable adverse events were followed until resolution or stabilization of the adverse event. Adverse Event (AE): An adverse event (AE) is any untoward medical occurrence in a patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. Abnormal laboratory values or diagnostic test results constitute adverse events only if they are determined to be of clinical significance or require treatment or further diagnostic tests. Adverse events are reported for all patients, based on starting dose	11.1% 1/9 • Patients were followed for AEs from first dose of study treatment, throughout the study, and through 30 days of the last study treatment, an average of 16 months. Participants removed from study for unacceptable adverse events were followed until resolution or stabilization of the adverse event. Adverse Event (AE): An adverse event (AE) is any untoward medical occurrence in a patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. Abnormal laboratory values or diagnostic test results constitute adverse events only if they are determined to be of clinical significance or require treatment or further diagnostic tests. Adverse events are reported for all patients, based on starting dose
Nervous system disorders Reversible Cerebral Vasoconstriction Syndrome	10.0% 1/10 • Patients were followed for AEs from first dose of study treatment, throughout the study, and through 30 days of the last study treatment, an average of 16 months. Participants removed from study for unacceptable adverse events were followed until resolution or stabilization of the adverse event. Adverse Event (AE): An adverse event (AE) is any untoward medical occurrence in a patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. Abnormal laboratory values or diagnostic test results constitute adverse events only if they are determined to be of clinical significance or require treatment or further diagnostic tests. Adverse events are reported for all patients, based on starting dose	0.00% 0/9 • Patients were followed for AEs from first dose of study treatment, throughout the study, and through 30 days of the last study treatment, an average of 16 months. Participants removed from study for unacceptable adverse events were followed until resolution or stabilization of the adverse event. Adverse Event (AE): An adverse event (AE) is any untoward medical occurrence in a patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. Abnormal laboratory values or diagnostic test results constitute adverse events only if they are determined to be of clinical significance or require treatment or further diagnostic tests. Adverse events are reported for all patients, based on starting dose
Gastrointestinal disorders Mouth sores	10.0% 1/10 • Patients were followed for AEs from first dose of study treatment, throughout the study, and through 30 days of the last study treatment, an average of 16 months. Participants removed from study for unacceptable adverse events were followed until resolution or stabilization of the adverse event. Adverse Event (AE): An adverse event (AE) is any untoward medical occurrence in a patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. Abnormal laboratory values or diagnostic test results constitute adverse events only if they are determined to be of clinical significance or require treatment or further diagnostic tests. Adverse events are reported for all patients, based on starting dose	0.00% 0/9 • Patients were followed for AEs from first dose of study treatment, throughout the study, and through 30 days of the last study treatment, an average of 16 months. Participants removed from study for unacceptable adverse events were followed until resolution or stabilization of the adverse event. Adverse Event (AE): An adverse event (AE) is any untoward medical occurrence in a patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. Abnormal laboratory values or diagnostic test results constitute adverse events only if they are determined to be of clinical significance or require treatment or further diagnostic tests. Adverse events are reported for all patients, based on starting dose
General disorders pain	0.00% 0/10 • Patients were followed for AEs from first dose of study treatment, throughout the study, and through 30 days of the last study treatment, an average of 16 months. Participants removed from study for unacceptable adverse events were followed until resolution or stabilization of the adverse event. Adverse Event (AE): An adverse event (AE) is any untoward medical occurrence in a patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. Abnormal laboratory values or diagnostic test results constitute adverse events only if they are determined to be of clinical significance or require treatment or further diagnostic tests. Adverse events are reported for all patients, based on starting dose	33.3% 3/9 • Patients were followed for AEs from first dose of study treatment, throughout the study, and through 30 days of the last study treatment, an average of 16 months. Participants removed from study for unacceptable adverse events were followed until resolution or stabilization of the adverse event. Adverse Event (AE): An adverse event (AE) is any untoward medical occurrence in a patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. Abnormal laboratory values or diagnostic test results constitute adverse events only if they are determined to be of clinical significance or require treatment or further diagnostic tests. Adverse events are reported for all patients, based on starting dose
Infections and infestations pneumonia	0.00% 0/10 • Patients were followed for AEs from first dose of study treatment, throughout the study, and through 30 days of the last study treatment, an average of 16 months. Participants removed from study for unacceptable adverse events were followed until resolution or stabilization of the adverse event. Adverse Event (AE): An adverse event (AE) is any untoward medical occurrence in a patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. Abnormal laboratory values or diagnostic test results constitute adverse events only if they are determined to be of clinical significance or require treatment or further diagnostic tests. Adverse events are reported for all patients, based on starting dose	11.1% 1/9 • Patients were followed for AEs from first dose of study treatment, throughout the study, and through 30 days of the last study treatment, an average of 16 months. Participants removed from study for unacceptable adverse events were followed until resolution or stabilization of the adverse event. Adverse Event (AE): An adverse event (AE) is any untoward medical occurrence in a patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. Abnormal laboratory values or diagnostic test results constitute adverse events only if they are determined to be of clinical significance or require treatment or further diagnostic tests. Adverse events are reported for all patients, based on starting dose
General disorders death due to disease progression	10.0% 1/10 • Patients were followed for AEs from first dose of study treatment, throughout the study, and through 30 days of the last study treatment, an average of 16 months. Participants removed from study for unacceptable adverse events were followed until resolution or stabilization of the adverse event. Adverse Event (AE): An adverse event (AE) is any untoward medical occurrence in a patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. Abnormal laboratory values or diagnostic test results constitute adverse events only if they are determined to be of clinical significance or require treatment or further diagnostic tests. Adverse events are reported for all patients, based on starting dose	0.00% 0/9 • Patients were followed for AEs from first dose of study treatment, throughout the study, and through 30 days of the last study treatment, an average of 16 months. Participants removed from study for unacceptable adverse events were followed until resolution or stabilization of the adverse event. Adverse Event (AE): An adverse event (AE) is any untoward medical occurrence in a patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. Abnormal laboratory values or diagnostic test results constitute adverse events only if they are determined to be of clinical significance or require treatment or further diagnostic tests. Adverse events are reported for all patients, based on starting dose
Nervous system disorders Intracranial bleeding	10.0% 1/10 • Patients were followed for AEs from first dose of study treatment, throughout the study, and through 30 days of the last study treatment, an average of 16 months. Participants removed from study for unacceptable adverse events were followed until resolution or stabilization of the adverse event. Adverse Event (AE): An adverse event (AE) is any untoward medical occurrence in a patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. Abnormal laboratory values or diagnostic test results constitute adverse events only if they are determined to be of clinical significance or require treatment or further diagnostic tests. Adverse events are reported for all patients, based on starting dose	0.00% 0/9 • Patients were followed for AEs from first dose of study treatment, throughout the study, and through 30 days of the last study treatment, an average of 16 months. Participants removed from study for unacceptable adverse events were followed until resolution or stabilization of the adverse event. Adverse Event (AE): An adverse event (AE) is any untoward medical occurrence in a patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. Abnormal laboratory values or diagnostic test results constitute adverse events only if they are determined to be of clinical significance or require treatment or further diagnostic tests. Adverse events are reported for all patients, based on starting dose
Gastrointestinal disorders Constipation	0.00% 0/10 • Patients were followed for AEs from first dose of study treatment, throughout the study, and through 30 days of the last study treatment, an average of 16 months. Participants removed from study for unacceptable adverse events were followed until resolution or stabilization of the adverse event. Adverse Event (AE): An adverse event (AE) is any untoward medical occurrence in a patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. Abnormal laboratory values or diagnostic test results constitute adverse events only if they are determined to be of clinical significance or require treatment or further diagnostic tests. Adverse events are reported for all patients, based on starting dose	11.1% 1/9 • Patients were followed for AEs from first dose of study treatment, throughout the study, and through 30 days of the last study treatment, an average of 16 months. Participants removed from study for unacceptable adverse events were followed until resolution or stabilization of the adverse event. Adverse Event (AE): An adverse event (AE) is any untoward medical occurrence in a patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. Abnormal laboratory values or diagnostic test results constitute adverse events only if they are determined to be of clinical significance or require treatment or further diagnostic tests. Adverse events are reported for all patients, based on starting dose
Respiratory, thoracic and mediastinal disorders shortness of breath	0.00% 0/10 • Patients were followed for AEs from first dose of study treatment, throughout the study, and through 30 days of the last study treatment, an average of 16 months. Participants removed from study for unacceptable adverse events were followed until resolution or stabilization of the adverse event. Adverse Event (AE): An adverse event (AE) is any untoward medical occurrence in a patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. Abnormal laboratory values or diagnostic test results constitute adverse events only if they are determined to be of clinical significance or require treatment or further diagnostic tests. Adverse events are reported for all patients, based on starting dose	11.1% 1/9 • Patients were followed for AEs from first dose of study treatment, throughout the study, and through 30 days of the last study treatment, an average of 16 months. Participants removed from study for unacceptable adverse events were followed until resolution or stabilization of the adverse event. Adverse Event (AE): An adverse event (AE) is any untoward medical occurrence in a patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. Abnormal laboratory values or diagnostic test results constitute adverse events only if they are determined to be of clinical significance or require treatment or further diagnostic tests. Adverse events are reported for all patients, based on starting dose

Other adverse events

Additional Information

Dr. Jennifer Chan

DFCI

Phone: 617-632-6315

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place