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Navitoclax and Abiraterone Acetate With or Without Hydroxychloroquine in Treating Patients With Progressive Metastatic Castrate Refractory Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01828476
Recruitment Status : Terminated (The Investigator left the organization.)
First Posted : April 10, 2013
Results First Posted : March 31, 2017
Last Update Posted : May 4, 2017
Sponsor:
Collaborators:
Rutgers Cancer Institute of New Jersey
National Cancer Institute (NCI)
AbbVie
Information provided by (Responsible Party):
Rutgers, The State University of New Jersey

Brief Summary:

The purpose of this study is to assess the effect of combining abiraterone with medicines that may block some of the ways that cells become resistant to abiraterone. The investigators hope that these combinations of medicines will result in prostrate cancer cells dying.

This study will see if overcoming diseases resistance to abiraterone will restore sensitivity to androgen deprivation therapy.


Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: Abiraterone Drug: ABT-263 Drug: Hydroxychloroquine Phase 2

Detailed Description:

Subjects will be either treated on one of the earlier dosing regimens or randomly assigned to one of two groups or ARMs of this study.

ARM A will receive Abiraterone with ABT-263.

ARM B will receive Abiraterone with both ABT-263 and Hydroxychloroquine

In the beginning of the study a total of 18 patients may get one of three dose levels. A total of nine (9) patients per each arm will be started at a low dose and given increasing doses if no side effects are seen. In this part of the study three patients will be enrolled at each dose level for each individual arm starting with Arm A followed by Arm B.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 13 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of ABT-263/Abiraterone (Arm A) or ABT-263/Abiraterone and Hydroxychloroquine (Arm B) in Patients With Metastatic Castrate Refractory Prostate Cancer (CRPC) and Progression Following Chemotherapy and Abiraterone
Study Start Date : June 2013
Actual Primary Completion Date : February 2016
Actual Study Completion Date : March 3, 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: ARM A
Abiraterone with ABT-263
Drug: Abiraterone
ARM A(Abiraterone with ABT-263) and ARM B(Abiraterone with both ABT-263 and Hydroxychloroquine)

Drug: ABT-263
ARM A(Abiraterone with ABT-263) and ARM B(Abiraterone with both ABT-263 and Hydroxychloroquine)

Experimental: ARM B
Abiraterone with both ABT-263 and Hydroxychloroquine
Drug: Abiraterone
ARM A(Abiraterone with ABT-263) and ARM B(Abiraterone with both ABT-263 and Hydroxychloroquine)

Drug: ABT-263
ARM A(Abiraterone with ABT-263) and ARM B(Abiraterone with both ABT-263 and Hydroxychloroquine)

Drug: Hydroxychloroquine
ARM B(Abiraterone with both ABT-263 and Hydroxychloroquine)




Primary Outcome Measures :
  1. Biochemical Response to ABT-263 and Abiraterone and to ABT-263 in Combination With Hydroxychloroquine and Abiraterone in Patients That Are Progressing on Abiraterone [ Time Frame: 5 years ]
    Characterize "biochemical response" to ABT-263 and Abiraterone and to ABT-263 in combination with hydroxychloroquine and Abiraterone by looking at PSA levels.


Secondary Outcome Measures :
  1. Time to PSA Progression [ Time Frame: 5 years ]
  2. Progression Free Survival [ Time Frame: 5 years ]
  3. Measurable Tumor Response in Patients With Measurable Disease [ Time Frame: 5 years ]
  4. Circulating Tumor Cells Pre-enrollment and During Therapy [ Time Frame: 5 years ]
  5. Bcl-2 Family Protein Expression (Bcl-2, Bcl-XL, MCL-1) in Paraffin Blocks When Available by Immunohistochemistry [ Time Frame: 5 years ]
  6. Biomarkers of Autophagy Modulation by EM; and LC3, and/or p62 by Immunoblotting in PBMC and Tumor Tissue When Available [ Time Frame: 5 years ]
  7. Overall Survival [ Time Frame: 5 years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have had evidence of disease progression while receiving primary androgen suppression therapy by orchiectomy or other primary hormonal therapy and abiraterone (Specifically, patients can have received multiple prior additional androgen axis targeting agents including enzalutamide, and prior chemotherapy, but must have had progression (as defined in 5.1.2) while receiving abiraterone either currently or in the past). Patients currently on abiraterone may continue with the start of the study drug(s).
  • Patients must have evidence of disease progression during current or prior therapy with abiraterone with either:

    1. Biochemical progression as defined as rising PSA from a nadir or baseline (whichever was lowest) confirmed on a second determination at least 1 week later that must be higher than the first and must have reached ≥2ng/ml (if no other evidence of progression); or
    2. New Metastases on bone scan (at least 2); or
    3. Progression of measurable disease on CT scan by RECIST criteria
  • Age >18 years and an estimated life expectancy of at least 6 months.
  • Treatment with at least 2 months of abiraterone prior to progression
  • ECOG performance status ≤ 2. (See Appendix A)
  • Patients must be ≥ 4 weeks since completing their prior therapy (including surgery, radiation therapy or investigational therapy (including targeted small molecule agents)). All previous clinically significant treatment-related toxicities have resolved to ≤ Grade 1. Patients must be ≥ 4 weeks since prior therapy with an anti-androgen
  • Adequate renal function (serum creatinine ≤ 2.0 mg/dL or creatinine clearance ≥50 ml/min)
  • Total bilirubin must be within 1.5 X the normal institutional limits. If total bilirubin is outside the normal institutional limits, assess direct bilirubin. The direct bilirubin must be within normal parameters. Transaminases (SGOT and/or SGPT) must be less than 1.5X ULN concomitant with alkaline phosphatase less than 5X the ULN.
  • An ANC >1500/μl, hemoglobin > 8.5 g/dl, and platelet count >100,000/mm3 are required.
  • Serum testosterone (total) less than 25 ng/ml at time of enrollment.
  • Bisphosphonates/RANK-ligand inhibitor allowed if started prior to study treatment
  • Patient must consent to using effective contraception while on treatment and for 3 months thereafter
  • Subject must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures

Exclusion Criteria:

  • Known infection with HIV or subject has tested positive for HIV (due to potential drug-drug interactions between anti-retroviral inhibitors and ABT-263, as well as anticipated ABT-263 mechanism based lymphopenia that may potentially increase the risk of opportunistic infections and potential drug-drug interactions with certain anti infective agents). Patients without prior HIV testing will not be required to be tested.
  • Second primary malignancy except most situ carcinoma (e.g. adequately treated non-melanomatous carcinoma of the skin) or other malignancy treated at least 5 years previously with no evidence of recurrence.
  • Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
  • Subject exhibits evidence of other clinically significant uncontrolled condition(s) including, but not limited to:

    • active systemic fungal infection;
    • diagnosis of fever and neutropenia within 1 week prior to study drug administration
  • Patients must discontinue all herbal supplements at a minimum of one week prior to initiation of therapy (such information will be collected on each patient
  • Requirement for routine use of hematopoietic growth factors (including granulocyte colony stimulating factor, granulocyte macrophage colony stimulating factor, or interleukin-11) or platelet transfusions to maintain absolute neutrophil counts or platelets counts above the required thresholds for study entry.
  • Patient has an underlying, predisposing condition of bleeding or currently exhibits signs of bleeding. The subject has a recent history of non-chemotherapy induced thrombocytopenic associated bleeding within 1 year prior to the first dose of study drug.
  • History or symptoms of cardiovascular disease (NYHA Class 2, 3, or 4; see Appendix B, New York Heart Association Criteria) within the last 6 months, particularly coronary artery disease, arrhythmias, or conduction defects with risk of cardiovascular instability, uncontrolled hypertension, clinically significant pericardial effusion, or congestive heart failure.
  • Hypersensitivity to 4-aminoquinoline compounds, including hydroxychloroquine sulfate, chloroquine phosphate and amodiaquine.
  • Prior history of treatment with ABT-263
  • Known G-6PDH deficiency
  • Retinal or visual field changes from prior 4-aminoquinoline compound use such as hydroxychloroquine sulfate, chloroquine phosphate and amodiaquine.
  • Patients presenting with untreated cord compression are not eligible (patients with prior treatment and stability will be eligible)
  • Concurrent use of other investigational agent
  • Subject has undergone an allogeneic stem cell transplant
  • Subject has active peptic ulcer disease or other hemorrhagic esophagitis/gastritis
  • Subject has a significant history of cardiovascular disease (e.g., MI, thrombotic or thromboembolic event in the last 6 months), renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, or hepatic disease that in the opinion of the Investigator would adversely affect his/her participating in this study. Subject has received a biologic agent for anti-neoplastic intent within 30 days prior to the first dose of study drug.
  • Subject is currently receiving or requires anticoagulation therapy (e.g., warfarin at any dose) or any drugs (e.g., aspirin, clopidogrel, etc) or herbal supplements that affect platelet function, with the exception of low molecular weight heparin or heparin that are used to maintain the patency of a catheter.
  • Subject has received aspirin or warfarin within 7 days prior to the first dose of study drug.
  • Subject has consumed grapefruit or grapefruit products within 3 days prior to the first dose of study drug.
  • Received potent CYP3A inhibitors (e.g., ketoconazole) or inducers (substrates of CYP2D6) within 7 days prior to the first dose of study drug.
  • Subject has received rifampin within 4 days prior to first dose of ABT-263

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01828476


Locations
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United States, New Jersey
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States, 08901
Sponsors and Collaborators
Rutgers, The State University of New Jersey
Rutgers Cancer Institute of New Jersey
National Cancer Institute (NCI)
AbbVie
Investigators
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Principal Investigator: Robert DiPaola, MD Rutgers, The State University of New Jersey
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Responsible Party: Rutgers, The State University of New Jersey
ClinicalTrials.gov Identifier: NCT01828476    
Other Study ID Numbers: 081214
Pro2013002775 ( Other Identifier: Rutgers IRB # )
P30CA072720 ( U.S. NIH Grant/Contract )
NCI-2013-02403 ( Other Identifier: NCI Trial ID )
First Posted: April 10, 2013    Key Record Dates
Results First Posted: March 31, 2017
Last Update Posted: May 4, 2017
Last Verified: March 2017
Keywords provided by Rutgers, The State University of New Jersey:
prostate cancer
hormone-resistant prostate cancer
recurrent prostate cancer
stage IV prostate cancer
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Hydroxychloroquine
Navitoclax
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents
Antineoplastic Agents