AzTrials
AzTrials

CirrhosisPhase 1NCT02143401

Navitoclax and Sorafenib Tosylate in Treating Patients With Relapsed or Refractory Solid Tumors

A Phase 1 study testing Laboratory Biomarker Analysis, Navitoclax and Pharmacological Study in people with Cirrhosis and Hepatitis B Infection, run by National Cancer Institute (NCI) at 10 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This phase I trial studies the side effects and the best dose of navitoclax when given together with sorafenib tosylate in treating patients with solid tumors that have returned (relapsed) or do not respond to treatment (refractory). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Laboratory Biomarker Analysis, Navitoclax and Pharmacological Study
Could I receive a placebo?
No, everyone receives an active treatment
How many people
29 participants
Where
10 sitesUnited States
Study dates
30 Jan 2015to 21 Mar 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • For Dose Escalation Cohort: Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
  • For Dose Expansion Cohort: HCC patients only: HCC confirmed by biopsy OR diagnosed by clinical and radiologic criteria; all of the following criteria must be met or a biopsy is required:
  • Known cirrhosis or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
  • Hypervascular liver masses > 2 cm, and either serum alpha-fetoprotein (AFP) > 400 ng/ml
  • AFP > three times normal and doubling in value in the antecedent 3 months
  • In the expansion cohort, prior treatment with sorafenib as first-line therapy allowed
Show all 37Show fewer
  • Any number of the following prior therapies is allowed:
  • Chemotherapy >= 28 days prior to registration
  • Mitomycin C/nitrosoureas >= 42 days prior to registration
  • Immunotherapy >= 28 days prior to registration
  • Biologic therapy >= 28 days prior to registration
  • Targeted therapy >= 28 days prior to registration
  • Radiation therapy >= 28 days prior to registration
  • Radiation to < 25% of bone marrow
  • HCC patients only: Prior regional treatments for liver metastasis are permitted including:
  • Selective internal radiation therapy such as brachytherapy, cyber knife, radiolabeled microsphere embolization, etc.
  • Hepatic artery chemoembolization
  • Hepatic artery embolization
  • Hepatic artery infusional chemotherapy
  • Radiofrequency ablation
  • NOTE: patients must be >= 4 weeks from treatment and show progressive measurable/evaluable disease in the liver after regional therapy or must have measurable disease outside the liver
  • HCC patients only: Child Pugh class A or B7 liver disease
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Life expectancy of > 3 months
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL (patients may be treated with hematopoietic growth factors to achieve or maintain this level)
  • Hemoglobin >= 9.0 g/dL
  • International normalized ratio (INR) =< 1.4
  • Platelets >= 100,000/mm^3
  • Total bilirubin =< 1.5 x ULN (institutional upper limit of normal) (patients with Gilbert's syndrome may have direct bilirubin > 2.5 x ULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN
  • Serum creatinine =< 1.5 x ULN
  • Able to swallow and retain oral medication
  • Negative serum pregnancy test =< 7 days prior to registration for women of childbearing potential
  • NOTE: women will be considered not of childbearing potential if they are surgically sterile (bilateral oophorectomy or hysterectomy) and/or post-menopausal (amenorrheic for at least 12 months)
  • Ability to understand and the willingness to sign a written informed consent document
  • Willing to provide tissue samples for correlative research purposes

Who cannot join

  • Unresolved toxicity of National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI CTCAE v 4.0) grade 2 or higher from previous anti-cancer therapy, except alopecia
  • Receiving any other investigational agents =< 28 days prior to registration
  • Known brain metastases (even if treated)
  • Known portal hypertension or history of variceal bleeding; these patients are felt to be at increased risk of bleeding if they experience navitoclax-induced thrombocytopenia
  • Inadequately controlled hypertension (systolic blood pressure of > 150 mmHg or diastolic pressure > 90 mmHg on anti-hypertensive medications)
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to navitoclax or sorafenib
Show all 28Show fewer
  • Current use of anticoagulation; NOTE: use of low-dose anticoagulation medications that are used to maintain the patency of a central intravenous catheter is allowed
  • Corrected QT (QTc) interval > 480 msec on baseline electrocardiogram (EKG)
  • Documented history of prolonged QTc interval =< 6 months prior to registration
  • Receiving any medications that prolong the QTc and have a known risk for Torsades de pointes; providers should use caution with drugs with possible increased risk for Torsades de pointes; NOTE: patient will be eligible if they can be taken off these medications prior to initiation of therapy and no less than 4 half-lives of the medication
  • Current use of certain concomitant medications due to mechanistic-based platelet toxicities from navitoclax: clopidogrel, ibuprofen, tirofiban and other anticoagulants, drugs or herbal supplements that effect platelet function; NOTE: antiplatelet use is prohibited during the use of navitoclax; subjects who have previously received aspirin therapy for thrombosis prevention may resume a low dose (i.e., maximum 100 mg QD) of aspirin if platelet counts are stable (>= 50,000/mm^3) through 6 weeks of navitoclax administration; all decisions regarding treatment with aspirin therapy will be determined by the principal investigator in conjunction with the medical monitor
  • Current use of strong CYP3A inhibitors such as ketoconazole, itraconazole, voriconazole, posaconazole, nefazodone, and clarithromycin are prohibited; NOTE: moderate inhibitors of CYP3A4 should be used with caution; navitoclax is a moderate inhibitor of CYP2C8 and a strong inhibitor of CYP2C9; caution should be exercised when dosing navitoclax concurrently with CYP2C8 and CYP2C9 substrates; common CYP2C8 substrates include paclitaxel, statins and repaglinide; CYP2C9 substrates include celecoxib, phenytoin and warfarin; when possible, investigators should switch to alternative medications or monitor the patients closely
  • Concurrent use of strong CYP3A4/5 inducers such as carbamazepine, phenytoin, rifampin, and St. John's wort are prohibited
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Any of the following:
  • Pregnant women
  • Nursing women
  • Women of childbearing potential who are unwilling to employ adequate contraception; NOTE: should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; the effects of navitoclax on the developing human fetus are unknown; for this reason and because other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception using one of the methods listed below prior to study entry, for the duration of study participation, and up to 90 days following completion of therapy:
  • Total abstinence from sexual intercourse (minimum one complete menstrual cycle prior to study drug administration)
  • Vasectomized male subject or vasectomized partner of female subjects
  • Hormonal contraceptives (oral, parenteral, transdermal or vaginal ring) for at least 3 months prior to study drug administration; if the subject is currently using a hormonal contraceptive, she should also use a barrier method during this study and for 1 month after study completion
  • Intrauterine device (IUD)
  • Double-barrier method: male condom plus diaphragm or vaginal cap with spermicide (contraceptive sponge, jellies or creams)
  • Additionally, male subjects (including those who are vasectomized) whose partners are pregnant or might be pregnant must agree to use condoms for the duration of the study and for 90 days following completion of therapy
  • Human immunodeficiency virus (HIV)-positive patients on highly active antiretroviral therapy (HAART) are excluded due to possible drug-drug interactions with the investigational agent(s)
  • Underlying condition predisposing them to bleeding or currently exhibits signs of clinically significant bleeding
  • Recent history of non-chemotherapy-induced thrombocytopenic-associated bleeding =< 1 year prior to the registration
  • History of cardiovascular disease (e.g., myocardial infraction [MI], thrombotic or thromboembolic event in the last 6 months)

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

United States10 sites

  • UCHealth University of Colorado Hospital

    Aurora, Colorado, 80045

  • University of Maryland/Greenebaum Cancer Center

    Baltimore, Maryland, 21201

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

    New York, New York, 10032

  • Thomas Jefferson University Hospital

    Philadelphia, Pennsylvania, 19107

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

Other trials in United States

About this study

Official title: A Phase I Trial of ABT-263 (Navitoclax), a Bcl-2 Inhibitor, and Sorafenib (Nexavar) in Patients With Relapsed or Refractory Solid Organ Tumors

This phase I trial studies the side effects and the best dose of navitoclax when given together with sorafenib tosylate in treating patients with solid tumors that have returned (relapsed) or do not respond to treatment (refractory). Navitoclax and sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximum tolerated dose (MTD) of the combination of navitoclax and sorafenib tosylate (sorafenib) in patients with advanced solid tumors. (Dose escalation cohort) II. To better characterize the toxicity profile of the combination of navitoclax and sorafenib. (Dose expansion cohort)

SECONDARY OBJECTIVES:

  1. To identify any activity of this treatment combination in patients with metastatic cancer. (Dose escalation cohort) II. To seek preliminary evidence of activity of this treatment combination in patients with hepatoma. (Dose expansion cohort)

CORRELATIVE OBJECTIVES:

  1. To determine whether the combination of navitoclax and sorafenib induces apoptosis that can be detected by peripheral blood biomarker analysis. (Dose escalation cohort) II. To assess peripheral blood biomarkers and pharmacokinetics in a more homogenous population. (Dose expansion cohort) III. To determine whether treatment is associated with Mcl-1 down regulation in hepatocellular carcinoma (HCC) at the maximum tolerated dose (MTD). (Dose expansion cohort) IV. To assess in a preliminary fashion whether pretreatment tumor cell levels of Mcl-1 predict response to this regimen through serial biopsies. (Dose expansion cohort)

OUTLINE: This is a dose-escalation study of navitoclax.

Patients receive navitoclax orally (PO) once daily (QD) on days 1-21 (days 1-28 cycle of 1 only) and sorafenib tosylate PO twice daily (BID) on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months.

Being tested
Laboratory Biomarker Analysis, Navitoclax, Pharmacological Study, Sorafenib, Sorafenib Tosylate
Medical subject headings
Fibrosis, Hepatitis B, Hepatitis C, Neoplasm Metastasis, Carcinoma, Hepatocellular, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • NavitoclaxBiological

    Also called A-855071.0, ABT-263, BcI-2 Family Protein Inhibitor ABT-263

    Given PO

  • Pharmacological StudyOther

    Correlative studies

  • SorafenibDrug

    Also called BA4 43 9006, BAY 43 9006, BAY 43-9006, BAY 439006

    Given PO

  • Sorafenib TosylateDrug

    Also called BAY 43-9006 Tosylate, BAY 54 9085, BAY 54-9085, BAY 549085

    Given PO

Study groups in NCT02143401
Study groupRoleWhat they receive
Treatment (navitoclax, sorafenib tosylate)ExperimentalPatients receive navitoclax PO QD on days 1-21 (days 1-28 cycle of 1 only) and sorafenib tosylate PO BID on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Receives: Other: Laboratory Biomarker Analysis; Biological: Navitoclax; Other: Pharmacological Study; Drug: Sorafenib; Drug: Sorafenib Tosylate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum tolerated dose (MTD) of navitoclax

    Will be defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients) per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 4.0.

    Measured: 28 days

  2. Incidence of adverse events

    Will be graded per NCI CTCAE v. 4.0. The number and severity of all adverse events (overall, by dose-level, and by tumor group) will be tabulated and summarized in this patient population. The grade 3+ adverse events will also be described and summarized in a similar fashion.

    Measured: Up to 3 months

Secondary outcomes (6)

  1. Tumor response

    Will be assessed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.1. Response will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease. The waterfall plot may be used to display best tumor response. Exploratory analysis of the relationship between response and other clinical endpoints may be performed.

    Measured: Up to 3 months

  2. Time until any treatment related toxicity

    The data on time-related variables will be summarized descriptively.

    Measured: Up to 3 months

  3. Time until treatment related grade 3+ toxicity

    The data on time-related variables will be summarized descriptively.

    Measured: Up to 3 months

  4. Time until hematologic nadirs (white blood cell, absolute neutrophil count, platelets)

    The data on time-related variables will be summarized descriptively.

    Measured: Up to 3 months

  5. Time to progression

    The data on time-related variables will be summarized descriptively.

    Measured: Up to 3 months

  6. Time to treatment failure

    The data on time-related variables will be summarized descriptively.

    Measured: From registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by the patient, assessed up to 3 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 May 2014 (estimated)
  2. Study start30 Jan 2015
  3. Primary completion30 Nov 2022
  4. Study completion21 Mar 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
29 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02143401
Sponsor's protocol ID
NCI-2014-01043
Other IDs
NCI-2014-01043, MC1315, 9608, 9608, UM1CA186686
Status last verified
Nov 2024
First submitted
19 May 2014
Last updated
22 Nov 2024
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Laboratory Biomarker Analysis, Navitoclax and Pharmacological Study in people with Cirrhosis and Hepatitis B Infection, run by National Cancer Institute (NCI) at 10 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 37 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum tolerated dose (MTD) of navitoclax (time frame: 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02143401.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Nov 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in