A Study to testABI-009 in Patients With Metastatic, Unresectable, Low or Intermediate Grade Neuroendocrine Tumors of the Lung or Gastroenteropancreatic System

• Sponsor: Robert Ramirez (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03670030
• Collaborator: Aadi Bioscience, Inc. (Industry)
• Enrollment: 5
• Location: 1
• Arm: 1
• Actual Duration (Months): 27.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether ABI-009 will make advanced, malignant neuroendocrine tumor(s) of the lung, gastrointestinal tract and/or pancreas that cannot be removed by surgery smaller and slow the spread of your cancer in patients who have progressed or been intolerant to everolimus. All eligible participants will receive ABI-009, the study drug.

Condition or Disease	Intervention/Treatment	Phase
Neuroendocrine Tumors	Drug: ABI-009	Phase 2

Detailed Description

ABI-009, human albumin-bound rapamycin, is an experimental drug. "Experimental" means that the drug has not been approved by the Food and Drug Administration (FDA).

Rapamycin, the active part of the drug, inhibits a biological pathway (mTOR) that certain cancers use to grow. Rapamycin and similar types of drugs have been used in many other tumors, including advanced renal cell carcinoma. A standard mTOR inhibitor used in neuroendocrine tumors is everolimus. The human albumin component of ABI-009 may allow rapamycin to reach cancer cells more effectively.

ABI-009 has not been approved for the treatment of advanced, malignant neuroendocrine tumors of the lung, gastrointestinal tract and/or pancreas. The information from this study might help us identify if ABI-009 is safe and effective in this disease.

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pilot Phase 2 Study of Albumin-bound Rapamycin Nanoparticles, ABI-009, in Patients With Metastatic, Unresectable, Low or Intermediate Grade Neuroendocrine Tumors of the Lung or Gastroenteropancreatic System
• Actual Study Start Date: Nov 5, 2018
• Actual Primary Completion Date: Jan 1, 2021
• Actual Study Completion Date: Feb 26, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ABI-009 In this study, you will receive ABI-009 given through a vein (intravenous) once weekly for 2 weeks (on days 1 and 8) followed by a week of rest in a 21-day cycle.	Drug: ABI-009; rapamycin protein-bound nanoparticles for injectable suspension (albumin bound); Other Names: nab-rapamycin

Outcome Measures

Primary Outcome Measures

1. Disease Control Rate at 6 Months Per RECIST v1.1. [6 months]

   Disease control rate at 6 months is the proportion of patients who have partial or complete response or stable disease at 6 months. Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Secondary Outcome Measures

1. Percent of Subjects Experiencing Adverse Events [Continuous from the signing of the informed consent to 28 days after last study treatment, on average 6 months]

   Percent of subjects with >=5% adverse events or grades 3 or 4 adverse events

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Unresectable or metastatic patients with typical or atypical carcinoid tumors of the lung or low or intermediate grade gastroenteropancreatic neuroendocrine tumors (GEPNETs).

2. Patients must have measurable disease per RECIST 1.1.

3. Patients must have progressed on everolimus or been intolerant to everolimus.

4. Patients, ≥18 years old, must have Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.

5. Concurrent use of somatostatin analogs (SSAs) is allowed if currently used for symptom control.

6. Adequate liver function:

7. Total bilirubin ≤1.5 x upper limit of normal (ULN) mg/dL

8. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x ULN (<5 x ULN if the patient has liver metastases).

9. Adequate renal function:

1. Serum creatinine ≤2 x ULN or creatinine clearance >50 cc/hr (Cockroft-Gault).

1. Adequate biological parameters:

2. Absolute neutrophil count (ANC) ≥1.5 × 109/L

3. Platelet count ≥100,000/mm3 (100 × 109/L)

4. Hemoglobin ≥9 g/dL.

5. Fasting serum triglyceride ≤300 mg/dL; fasting serum cholesterol ≤350 mg/dL.

6. Male or non-pregnant and non-breast feeding female:

• Females of child-bearing potential must agree to use effective contraception without interruption from 28 days prior to starting investigational product (IP) throughout 3 months after last dose of IP and have a negative serum pregnancy test (β-hCG) result at screening and agree to ongoing pregnancy testing during the course of the study, and after the end of study treatment. A second form of birth control is required even if she has had a tubal ligation.

• Male patients must practice abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study and throughout 3 months after last dose of IP. A second form of birth control is required even if he has undergone a successful vasectomy.

1. Life expectancy of >3 months, as determined by the investigator.

2. Ability to understand and sign informed consent.

3. Willingness and ability to comply with scheduled visits, laboratory tests, and other study procedures.

Exclusion Criteria:

1. Patients currently undergoing anti-cancer therapy for neuroendocrine tumors (other than SSAs for symptoms).

2. History of allergic reactions to compounds of similar chemical or biologic composition to ABI-009.

3. Known active uncontrolled or symptomatic central nervous system (CNS) metastases. A patient with controlled and asymptomatic CNS metastases may participate in this study. As such, the patient must have completed any prior treatment for CNS metastases ?28 days (including radiotherapy and/or surgery) prior to start of treatment in this study and should not be receiving chronic corticosteroid therapy for the CNS metastases.

4. Active gastrointestinal bleeding.

5. Uncontrolled serious medical or psychiatric illness. Patients with a "currently active" second malignancy other than non-melanoma skin cancers, carcinoma in situ of the cervix, resected incidental prostate cancer (staged pathological tumor-2 (pT2) with Gleason Score ≤6 and postoperative prostate-specific antigen (PSA) <0.5 ng/mL), or other adequately treated carcinoma-in-situ are ineligible. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for ≥1 year).

6. Recent infection requiring systemic anti-infective treatment that was completed ≤14 days prior to enrollment (with the exception of uncomplicated urinary tract infection or upper respiratory tract infection).

7. Uncontrolled diabetes mellitus as defined by HbA1c >8% despite adequate therapy.

8. Unstable coronary artery disease or myocardial infarction during preceding 6 months.

9. Patients with history of interstitial lung disease and/or pneumonitis, or pulmonary hypertension.

10. Use of strong inhibitors and inducers of CYP3A4 within the 14 days prior to receiving the first dose of ABI-009. Additionally, use of any known CYP3A4 substrates with narrow therapeutic window (such as fentanyl, alfentanil, astemizole, cisapride, dihydroergotamine, pimozide, quinidine, terfanide) within the 14 days prior to receiving the first dose of ABI-009.

11. Known Human Immunodeficiency Virus (HIV).

12. Known active Hepatitis B or Hepatitis C.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ochsner Clinic Foundation	New Orleans	Louisiana	United States	70121

Sponsors and Collaborators

• Robert Ramirez
• Aadi Bioscience, Inc.

Investigators

• Principal Investigator: Robert Ramirez, DO, Ochnser Clinic Foundation

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 13, 2019
• Informed Consent Form - Jan 6, 2020

More Information

Publications

None provided.

• Responsible Party: Robert Ramirez, Principal Investigator, Ochsner Health System
• ClinicalTrials.gov Identifier: NCT03670030
• Other Study ID Numbers: NET-001
• First Posted: Sep 13, 2018
• Last Update Posted: Jun 10, 2021
• Last Verified: May 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Neuroendocrine Tumors; Lung Neoplasms; Sirolimus

Study Results

Participant Flow

Arm/Group Title	ABI-009
Arm/Group Description	In this study, you will receive ABI-009 given through a vein (intravenous) once weekly for 2 weeks (on days 1 and 8) followed by a week of rest in a 21-day cycle. ABI-009: rapamycin protein-bound nanoparticles for injectable suspension (albumin bound)
Period Title: Overall Study
STARTED	5
COMPLETED	5
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	ABI-009
Arm/Group Description	In this study, you will receive ABI-009 given through a vein (intravenous) once weekly for 2 weeks (on days 1 and 8) followed by a week of rest in a 21-day cycle. ABI-009: rapamycin protein-bound nanoparticles for injectable suspension (albumin bound)
Overall Participants	5
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	2 40%
>=65 years	3 60%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	64
Sex: Female, Male (Count of Participants)
Female	2 40%
Male	3 60%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 40%
White	3 60%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	5 100%

Outcome Measures

1. Primary Outcome

Title	Disease Control Rate at 6 Months Per RECIST v1.1.
Description	Disease control rate at 6 months is the proportion of patients who have partial or complete response or stable disease at 6 months. Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ABI-009
Arm/Group Description	In this study, you will receive ABI-009 given through a vein (intravenous) once weekly for 2 weeks (on days 1 and 8) followed by a week of rest in a 21-day cycle. ABI-009: rapamycin protein-bound nanoparticles for injectable suspension (albumin bound)
Measure Participants	5
Count of Participants [Participants]	5 100%

2. Secondary Outcome

Title	Percent of Subjects Experiencing Adverse Events
Description	Percent of subjects with >=5% adverse events or grades 3 or 4 adverse events
Time Frame	Continuous from the signing of the informed consent to 28 days after last study treatment, on average 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ABI-009
Arm/Group Description	In this study, you will receive ABI-009 given through a vein (intravenous) once weekly for 2 weeks (on days 1 and 8) followed by a week of rest in a 21-day cycle. ABI-009: rapamycin protein-bound nanoparticles for injectable suspension (albumin bound)
Measure Participants	5
Count of Participants [Participants]	5 100%

Adverse Events

Time Frame	Continuous from the signing of the informed consent to 28 days after last study treatment, on average 6 months
Adverse Event Reporting Description	Percent of subjects with >=5% adverse events or grades 3 or 4 adverse events
Arm/Group Title	ABI-009
Arm/Group Description	In this study, you will receive ABI-009 given through a vein (intravenous) once weekly for 2 weeks (on days 1 and 8) followed by a week of rest in a 21-day cycle. ABI-009: rapamycin protein-bound nanoparticles for injectable suspension (albumin bound)
All Cause Mortality
	ABI-009
	Affected / at Risk (%)	# Events
Total	0/5 (0%)
Serious Adverse Events
	ABI-009
	Affected / at Risk (%)	# Events
Total	3/5 (60%)
Gastrointestinal disorders
Diarrhea	1/5 (20%)	1
Infections and infestations
Fever	1/5 (20%)	1
Metabolism and nutrition disorders
Dehydration	1/5 (20%)	1
Nervous system disorders
Dementia	1/5 (20%)	1
Other (Not Including Serious) Adverse Events
	ABI-009
	Affected / at Risk (%)	# Events
Total	5/5 (100%)
Blood and lymphatic system disorders
Anemia	3/5 (60%)	21
Platelet count decrease	3/5 (60%)	25
Cardiac disorders
Hypertension	1/5 (20%)	6
General disorders
Fatigue	3/5 (60%)	9
Metabolism and nutrition disorders
Dehydration	1/5 (20%)	1
Hypercalcemia	3/5 (60%)	6
Hyperglycemia	2/5 (40%)	12
Hyperkalemia	1/5 (20%)	3
Hypoalbuminemia	2/5 (40%)	5
Hypokalemia	3/5 (60%)	9
Hypophosphatemia	1/5 (20%)	3
Nervous system disorders
Confusion	1/5 (20%)	1
Encephalopathy	1/5 (20%)	1
Renal and urinary disorders
Urinary tract infection	1/5 (20%)	3
Skin and subcutaneous tissue disorders
Rash	3/5 (60%)	13

Limitations/Caveats

Early termination leading to small numbers affecting usefulness interpreting results. Only 2 patients were eligible for analysis of primary outcome.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.