AL101 Before Surgery for the Treatment of Notch Activated Adenoid Cystic Cancer

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Brief Title

AL101 Before Surgery for the Treatment of Notch Activated Adenoid Cystic Cancer

Official Title

AL101 Prior to Standard-of-Care Surgery in Patients With Notch Activated Adenoid Cystic Carcinoma (ACC)

Brief Summary

      This phase Ib trial studies the side effects and possible benefits of AL101 before surgery in
      treating patients with notch activated adenoid cystic cancer. AL101 may stop the growth of
      tumor cells by blocking some of the enzymes needed for cell growth. Giving AL101 before
      surgery may help to control adenoid cystic cancer that has a NOTCH pathway activation.
    

Detailed Description

      PRIMARY OBJECTIVES:

      I. To evaluate the safety and feasibility of AL101 administered weekly for 6 to 8 weeks in
      the preoperative setting using National Cancer Institute (NCI)-Common Terminology Criteria
      for Adverse Events (CTCAE) version 5.0.

      II. To determine the differences between NICD1 levels by immunohistochemistry (IHC) in the
      post-treatment surgical specimens as compared to baseline in patients treated with AL101.

      SECONDARY OBJECTIVES:

      I. To evaluate the objective response rate (ORR) to AL101 by Response Evaluation Criteria in
      Solid Tumors (RECIST) 1.1 at 6 to 8 weeks.

      II. To assess percentage of patients undergoing the initially proposed surgery. III. To
      assess percentage of viable tumor cells in the surgical specimen (pathologic response)
      following AL101 treatment.

      EXPLORATORY OBJECTIVE:

      I. To evaluate pre- and post- treatment tumor and blood biomarkers and correlate with
      clinical and pathologic response and toxicity.

      OUTLINE:

      Patients receive AL101 intravenously (IV) over 60 minutes once weekly (QW) for 6-8 weeks in
      the absence of disease progression or unacceptable toxicity. Within 24-72 hours after the
      last infusion of AL101, patients undergo surgery per standard of care. Patients may continue
      AL101 after surgery at the discretion of the study doctor.

      After completion of study, patients are followed up within 6 weeks after surgery or within 30
      days after last dose of AL101, and then every 6 months thereafter.
    

Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

Incidence of adverse events

Secondary Outcome

 Overall response rate

Condition

Adenoid Cystic Carcinoma

Intervention

AL101

Study Arms / Comparison Groups

 Treatment (AL101)
Description:  Patients receive AL101 IV over 60 minutes QW for 6-8 weeks in the absence of disease progression or unacceptable toxicity. Within 24-72 hours after the last infusion of AL101, patients undergo surgery per standard of care. Patients may continue AL101 after surgery at the discretion of the study doctor.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

12

Start Date

November 30, 2021

Completion Date

April 19, 2023

Primary Completion Date

April 19, 2023

Eligibility Criteria

        Inclusion Criteria:

          -  Capable of giving signed informed consent which includes compliance with the
             requirements and restrictions listed in the informed consent and in this protocol

          -  Age >= 18 years old

          -  Histologically/cytological confirmed adenoid cystic carcinoma (ACC) of any primary
             site

          -  Evidence of NOTCH1 pathway activation as determined by NICD1 IHC nuclear staining in
             >= 70% of tumor cells

          -  Patients must have surgically resectable disease, either with a curative intent or for
             local control in the setting of metastatic disease, in the opinion of the treating
             physician

          -  Patients must be willing to undergo baseline biopsy to obtain tumor material

          -  Disease must be measurable by RECIST 1.1

          -  Performance status Eastern Cooperative Oncology Group (ECOG) 0 or 1

          -  Neutrophils < 1500/mm^3

          -  Platelet count < 100,000/mm^3

          -  Hemoglobin < 9 g/dL

          -  Total bilirubin > 1.5 upper limit of normal (ULN) (except known Gilbert's syndrome)

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) > 2.5 of upper
             limit of normality (ULN) OR > 5 ULN for patients with liver metastases

          -  Creatinine clearance < 40 mL/min (Calculation of creatinine clearance [CrCl] will be
             based on acceptable institution standard)

          -  Female patients with reproductive potential must practice two effective contraceptive
             measures for the duration of study drug therapy and for at least 90 days after
             completion of AL101 therapy. The two birth control methods can be either two barrier
             methods or a barrier method plus a hormonal method to prevent pregnancy. The following
             are considered adequate barrier methods of contraception: diaphragm, condom, copper
             intrauterine device, sponge, or spermicide. Appropriate hormonal contraceptives will
             include any registered and marketed contraceptive agent that contains an estrogen
             and/or a progestational agent (including oral, subcutaneous, intrauterine, or
             intramuscular agents)

          -  Male patients who are sexually active with women with reproductive potential must
             agree to use contraception for the duration of treatment and for at least 90 days
             after completion of AL101 therapy

        Exclusion Criteria:

          -  Prior radiotherapy, chemotherapy, or biologic therapy is allowed in patients with
             loco-regional recurrent disease, if administered at least 4 weeks prior to study
             enrollment

          -  Prior treatment with gamma-secretase inhibitor

          -  History of previous malignancy other than malignancy treated with curative intent and
             with no evidence of active disease >= 2 years before the first dose of study drug and
             of low potential risk for recurrence. Patients with the following diagnoses represents
             an exception and may enroll:

               -  Non-melanoma skin cancers with no current evidence of disease

               -  Melanoma in situ with no current evidence of disease

               -  Localized cancer of the prostate with prostate-specific antigen of < 0.1 ng/mL

               -  Treated or localized well-differentiated thyroid cancer

               -  Treated cervical carcinoma in situ

               -  Treated ductal/lobular carcinoma in situ of the breast

          -  Current or recent (within 2 months of investigational product administration)
             gastrointestinal disease such as disorders that increase the risk of diarrhea (e.g.:
             inflammatory bowel disease). Non-chronic conditions (e.g., infectious diarrhea) that
             are completely resolved for at least 2 weeks prior to starting investigational product
             are not exclusionary

          -  Evidence of clinically significant bleeding diathesis or coagulopathy (in the absence
             of therapeutic anticoagulation)

          -  Evidence of uncontrolled, active infection, requiring systemic anti-bacterial,
             anti-viral or anti-fungal therapy =< 7 days prior to administration of investigational
             product such as known active infection with hepatitis B and hepatitis C (HCV) at
             Screening

          -  Symptomatic central nervous system (CNS) metastases. Patients with asymptomatic CNS
             metastases as well as those with previously treated CNS metastases are eligible for
             enrollment in the study if at least four weeks has elapsed since last whole brain
             radiation treatment or at least two weeks has elapsed since last focal radiation
             treatment and the patient is deemed clinically stable by the investigator

          -  Unstable or severe uncontrolled medical condition (e.g., unstable cardiac or pulmonary
             function or uncontrolled diabetes) or any important medical illness or abnormal
             laboratory finding that would, in the investigator's judgment, increase the risk to
             the patient associated with his or her participation in the study

          -  Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) >= 480
             msec

          -  Female subjects who are pregnant or breast-feeding

          -  Hypersensitivity and/or history of allergy to the investigational product excipients
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Renata Ferrarotto, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT04973683

Organization ID

2021-0296

Secondary IDs

NCI-2021-05878

Responsible Party

Sponsor

Study Sponsor

M.D. Anderson Cancer Center


Study Sponsor

Renata Ferrarotto, Principal Investigator, M.D. Anderson Cancer Center


Verification Date

July 2021