ABI-009 Trial in Patients With Advanced Non-hematologic Malignancies

A Phase I Trial of ABI-009 (Nab-rapamycin) Administered Weekly in Patients With Advanced Non-hematologic Malignancies

To determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLTs) of ABI-009 given weekly; to characterize the toxicities of ABI-009; and to determine the pharmacokinetic parameters for ABI-009 when given on a weekly schedule.

Study Overview

• Status: Completed
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: ABI-009

Detailed Description

No extended description necessary

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Santa Monica, California, United States, 90403
      • Sarcoma Oncology Center
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas M.D. Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Each subject must meet the following criteria to be enrolled in this study.

1. Male and female patients with histologically or cytologically confirmed diagnosis of cancer which is not amenable to curative therapy.
2. Patients with advanced non-hematologic malignancies for whom no standard therapy exists.
3. Measurable disease by RECIST or evaluable disease (e.g., bone metastasis, pleural effusion, ascites, or lesions which do not fulfill RECIST criteria for metastatic disease)
4. Off all therapy (inclusive of investigational therapies) for at least 4 weeks prior to study drug administration OR off all daily or weekly therapy (inclusive of investigational therapies) for at least 2 weeks prior to study drug administration and without any side effects associated with these therapies.
5. Female patients of child-bearing potential must have a negative serum pregnancy test within 7 days prior to first study drug administration.
6. Female patients who are postmenopausal must have 12 months of amenorrhea, surgically sterile, or must agree to the use of a physical method of non-hormonal contraception.
7. Male patients must be surgically sterile or agree to the use of a barrier method of contraception.
8. Life expectancy of > 3 months.
9. ECOG Performance Status of 0-1.
10. Patients must be able to provide informed consent indicating knowledge of his/her disease process, the investigational nature of the therapy, alternatives, benefits, and risks including potential side effects.
11. Age ≥ 18 years of age.
12. No major surgery within 4 weeks before treatment with ABI-009. (A biopsy is not considered major surgery).
13. No chemotherapy, hormonal therapy, immunotherapy or radiotherapy within 4 weeks before treatment with ABI-009 (6 weeks for previous treatment with nitrosoureas, mitomycin, or extensive radiotherapy) and no immunosuppressive agents within 3 weeks before study entry (except corticosteroids used as antiemetics).
14. No immunosuppressive agents within 3 weeks before study entry (except corticosteroids used as antiemetics).

15. Required Initial Laboratory Data:

    • Hemoglobin > 9.0 g/dL
    • WBC ≥ 3,000/µl
    • ANC ≥ 1,500/µl
    • Platelet count ≥ 100,000/µl
    • Total Bilirubin ≤ ULN
    • SGOT (AST) SGPT (ALT) ≤ 1.5 x ULN ≤ 1.5 x ULN
    • Serum Cholesterol < 350 mg/dL
    • Serum Triglyceride < 300 mg/dL
16. Adequate renal function with serum creatinine < 1.5 mg/dL and/or creatinine clearance (cockroft formula) ≥ 60 mL/min.
17. No active alcohol abuse, drug addiction, or psychotic disorders.
18. No known concomitant genetic or acquired immunosuppressive diseases (such as AIDS).
19. If obese, a patient must be treated with doses calculated using his/her actual BSA (The physician must be comfortable treating at the full BSA dose regardless of BSA).

Exclusion Criteria:

Subjects who meet any of the following criteria will be excluded from the study.

1. Pregnant or nursing women.
2. History of allergic reactions attributed to compounds of similar chemical or biologic composition including macrolide (e.g. azithromycin, clarithromycin, dirithromycin, and erythromycin) and ketolide antibiotics.
3. Patients have not recovered from adverse affects of radiation therapy or investigational agent within previous 28 days.
4. Uncontrolled intercurrent illness that in the opinion of the investigator would limit compliance and tolerance to study requirements
5. Patients with known brain metastases or leptomeningeal tumor involvement.
6. Receiving any of the following: concomitant antitumor therapy or inhibitors of CYP3A4.
7. Patients with history of interstitial lung disease and/or pneumonitis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ABI-009	Drug: ABI-009; nab-rapamycin; Other Names: nab-rapamycin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLTs) of ABI-009 administered weekly and pharmacokinetic parameters for ABI-009.	End of Study (EOS) and Follow Up

Secondary Outcome Measures

Outcome Measure	Time Frame
Efficacy of ABI-009 in this patient population	End of Study (EOS) and Follow Up

Collaborators and Investigators

• Sponsor: Celgene
• Investigators: Principal Investigator: Ana M. Gonzalez, MD, M.D. Anderson Cancer Center; Principal Investigator: Sant P. Chawla, MD, Sarcoma Oncology Center

Publications and helpful links

General Publications

• Gonzalez-Angulo AM, Meric-Bernstam F, Chawla S, Falchook G, Hong D, Akcakanat A, Chen H, Naing A, Fu S, Wheler J, Moulder S, Helgason T, Li S, Elias I, Desai N, Kurzrock R. Weekly nab-Rapamycin in patients with advanced nonhematologic malignancies: final results of a phase I trial. Clin Cancer Res. 2013 Oct 1;19(19):5474-84. doi: 10.1158/1078-0432.CCR-12-3110.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2007
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): June 1, 2011

Study Registration Dates

• First Submitted: March 7, 2008
• First Submitted That Met QC Criteria: March 12, 2008
• First Posted (Estimate): March 13, 2008

Study Record Updates

• Last Update Posted (Actual): October 18, 2019
• Last Update Submitted That Met QC Criteria: October 16, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Sirolimus
• Other Study ID Numbers: CA401