Nab-Sirolimus in Combination With FOLFOX & BEV as 1st Line Therapy in Patients With Advanced or Metastatic Colorectal Cancer

NCT03439462 | Completed Phase 1 Results FDA Drug

• 1 other identifier: COLO-007
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 6

Brief Summary

A phase 1/2 multi-center investigation of nab-sirolimus (also known as ABI-009, nab-rapamycin) in combination with mFOLFOX6 and Bevacizumab as first-line therapy in patients with metastatic colorectal cancer

Conditions

Colorectal Cancer Metastatic

Outcome Measures

Primary Outcomes (2)

• Dose-limiting-toxicities (DLTs) (Phase 1)

  Dose-limiting-toxicities within the first 2 cycles of treatment with nab-sirolimus at various doses and schedule in combination with mFOLFOX6 and bevacizumab

  First 2 treatment cycles (2 months)

• Progression-free Survival at 6 Months (Phase 2) for All Patients, at the RP2D, as Well as Based on PTEN Status (Positive and Negative)

  The PFS rate at 6 months was estimated using the Kaplan-Meier method for a) all efficacy evaluable patients, b) patients receiving treatment at the RP2D, and c) based on PTEN status (positive or negative). Progression-free survival was defined as the time from the first day of study drug administration to disease progression or death due to any cause. Response evaluation was performed per RECIST v1.1, with the criteria for progression is at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.

  6 months

Secondary Outcomes (3)

• Disease Control Rate (DCR) (Phase 2) for All Patients, at the RP2D, as Well as Based on PTEN Status (Positive and Negative)

  Through study completion (up to 50 months)

• Median Progression-free Survival (Phase 2) for All Patients, at the RP2D, as Well as Based on PTEN Status (Positive and Negative)

  Through study completion (up to 50 months)

• Overall Response Rate (Phase 2) for All Patients, at the RP2D, as Well as Based on PTEN Status (Positive and Negative)

  Through study completion (up to 50 months)

Study Arms (1)

nab-sirolimus (also known as ABI-009, nab-rapamycin, albumin-bound rapamycin)

EXPERIMENTAL

Single arm, open-label, multi-institutional study to identify the RP2D and determine the efficacy and safety profile of nab-sirolimus administered as first-line therapy in combination with mFOLFOX6 and bevacizumab in patients with metastatic CRC.

Drug: nab-sirolimus

Interventions

nab-sirolimus DRUG

nab-sirolimus combined with mFOLFOX6 + bevacizumab

Also known as: bevacizumab, mFOLFOX6

nab-sirolimus (also known as ABI-009, nab-rapamycin, albumin-bound rapamycin)

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically confirmed advanced or metastatic colorectal cancers for whom chemotherapy is indicated.
• Patients must not have had prior chemotherapy for advanced or metastatic disease. Patients could have received adjuvant chemotherapy or adjuvant chemo-radiotherapy.
• Patients must have at least 1 measurable site of disease according to RECIST v1.1 that has not been previously irradiated. If the patient has had previous radiation to the marker lesion(s), there must be radiological evidence of progression since the radiation.
• Eligible patients, 18 years or older, with Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.
• Patients must not have been previously treated with an mTOR inhibitor.
• Adequate liver function:
• Total bilirubin ≤1.5 x upper limit of normal (ULN) mg/dL
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x ULN (\<5 x ULN if the patient has liver metastases).
• Adequate renal function:
• a. Serum creatinine ≤2 x ULN or creatinine clearance \>50 cc/hr (Cockroft-Gault).
• Adequate biological parameters:
• Absolute neutrophil count (ANC) ≥1.5 × 109/L
• Platelet count ≥100,000/mm3 (100 × 109/L)
• Hemoglobin ≥9 g/dL.
• Fasting serum triglyceride ≤300 mg/dL; fasting serum cholesterol ≤350 mg/dL.

You may not qualify if:

• History of severe and uncontrolled allergic reactions to bevacizumab
• Prior treatment with FOLFOX or bevacizumab within the preceding 4 weeks
• Patients currently receiving or have received anticancer therapies within 4 weeks of the start of study treatment (including chemotherapy, radiation therapy, antibody based therapy, etc.)
• Patients, who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study
• Chronic treatment with systemic steroids or another immunosuppressive agent; topical or inhaled corticosteroids are allowed
• 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).
• Patients who have any severe and/or uncontrolled medical or psychiatric conditions or other conditions that could affect their participation including:
• 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.
• Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤6 months prior to first study treatment, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease
• Pre-existing severely impaired lung function as defined as spirometry and DLCO that is 50% of the normal predicted value and/or O2 saturation that is 88% or less at rest on room air (Note: spirometry and PFTs not required to be performed unless clinically indicated).
• Uncontrolled diabetes as defined by fasting serum glucose \>1.5x ULN or by HbA1c \>8% despite adequate therapy.
• Any active (acute or chronic) or uncontrolled infection/ disorders.
• Nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with the study therapy. Note, controlled non-melanoma skin cancers, carcinoma in situ of the cervix, resected incidental prostate cancer, or other adequately treated carcinoma-in-situ may be eligible, after documented discussion with the sponsor / medical monitor.
• Known liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C).
• Patients with history of interstitial lung disease and/or pneumonitis, or pulmonary hypertension.

Sponsors & Collaborators

• Aadi Bioscience, Inc.: lead

Study Sites (6)

HonorHealth Research Institute

Scottsdale, Arizona, 85258, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

Location

Atlantic Health System/Morristown Medical Center

Morristown, New Jersey, 07962, United States

Location

Baylor Scott and White University Medical Center

Dallas, Texas, 75246, United States

Location

Seattle Cancer Care Alliance/University of Washington Medical Center

Seattle, Washington, 98109, United States

Location

MeSH Terms

Interventions

Bevacizumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Aadi Medical Information
• Organization: Aadi Bioscience, Inc.

MedInfo@aadibio.com

1-888-246-2234

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2018
• First Posted: February 20, 2018
• Study Start: July 1, 2018
• Primary Completion: August 16, 2022
• Study Completion: August 26, 2022
• Last Updated: January 2, 2024
• Results First Posted: January 2, 2024

Record last verified: 2023-11

Locations

US (6)