Prostate CancerPhase 2NCT01828476
Navitoclax and Abiraterone Acetate With or Without Hydroxychloroquine in Treating Patients With Progressive Metastatic Castrate Refractory Prostate Cancer
A Phase 2 study testing Abiraterone, ABT-263 and Hydroxychloroquine in people with Prostate Cancer, run by Rutgers, The State University of New Jersey at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- Abiraterone, ABT-263 and Hydroxychloroquine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2013to 3 Mar 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- 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
- New Metastases on bone scan (at least 2); or
- Progression of measurable disease on CT scan by RECIST criteria
- Age >18 years and an estimated life expectancy of at least 6 months.
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08901
About this study
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
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.
Read the 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.
- Conditions
- Prostate Cancer
- Being tested
- Abiraterone, ABT-263, Hydroxychloroquine
- Keywords
- prostate cancer, hormone-resistant prostate cancer, recurrent prostate cancer, stage IV prostate cancer
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AbirateroneDrug
ARM A(Abiraterone with ABT-263) and ARM B(Abiraterone with both ABT-263 and Hydroxychloroquine)
ABT-263Drug
ARM A(Abiraterone with ABT-263) and ARM B(Abiraterone with both ABT-263 and Hydroxychloroquine)
ARM B(Abiraterone with both ABT-263 and Hydroxychloroquine)
| Study group | Role | What they receive |
|---|---|---|
| ARM A | Experimental | Abiraterone with ABT-263 Receives: Drug: Abiraterone; Drug: ABT-263 |
| ARM B | Experimental | Abiraterone with both ABT-263 and Hydroxychloroquine Receives: Drug: Abiraterone; Drug: ABT-263; Drug: Hydroxychloroquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Biochemical Response to ABT-263 and Abiraterone and to ABT-263 in Combination With Hydroxychloroquine and Abiraterone in Patients That Are Progressing on Abiraterone
Characterize "biochemical response" to ABT-263 and Abiraterone and to ABT-263 in combination with hydroxychloroquine and Abiraterone by looking at PSA levels.
Measured: 5 years
Secondary outcomes (7)
Time to PSA Progression
Measured: 5 years
Progression Free Survival
Measured: 5 years
Measurable Tumor Response in Patients With Measurable Disease
Measured: 5 years
Circulating Tumor Cells Pre-enrollment and During Therapy
Measured: 5 years
Bcl-2 Family Protein Expression (Bcl-2, Bcl-XL, MCL-1) in Paraffin Blocks When Available by Immunohistochemistry
Measured: 5 years
Biomarkers of Autophagy Modulation by EM; and LC3, and/or p62 by Immunoblotting in PBMC and Tumor Tissue When Available
Measured: 5 years
Overall Survival
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2013 (estimated)
- Study startJun 2013
- Primary completionFeb 2016
- Study completion3 Mar 2016
Why it stopped: The Investigator left the organization.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by Rutgers, The State University of New JerseyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rutgers, The State University of New Jersey
- Sponsor type
- University, hospital or other
- Collaborators
- Rutgers Cancer Institute of New Jersey, National Cancer Institute (NCI), AbbVie
- Responsible party
- Sponsor
- Investigators
- Robert DiPaola, MD, Principal investigator, Rutgers, The State University of New Jersey
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01828476
- Sponsor's protocol ID
- 081214
- Other IDs
- Pro2013002775, P30CA072720, NCI-2013-02403
- Status last verified
- Mar 2017
- First submitted
- 26 Mar 2013
- Last updated
- 4 May 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01828476
- Acronym / sponsor ID
- 081214
- Conditions
- Prostate Cancer
- Keywords
- prostate cancer, hormone-resistant prostate cancer, recurrent prostate cancer, stage IV prostate cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The Investigator left the organization.
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Rutgers, The State University of New JerseyUniversity, hospital or other
- Collaborators
- Rutgers Cancer Institute of New Jersey, National Cancer Institute (NCI), AbbVie
- Study start
- Jun 2013
- Primary completion
- Feb 2016 (actual)
- Study completion
- 3 Mar 2016 (actual)
- First posted
- 10 Apr 2013 (estimated)
- Results
- Posted 31 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ARM A | Experimental | Drug: Abiraterone, Drug: ABT-263Abiraterone with ABT-263 |
| ARM B | Experimental | Drug: Abiraterone, Drug: ABT-263, Drug: HydroxychloroquineAbiraterone with both ABT-263 and Hydroxychloroquine |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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:
- 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)
Key exclusion criteria (24 listed)
- 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:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AbirateroneARM A(Abiraterone with ABT-263) and ARM B(Abiraterone with both ABT-263 and Hydroxychloroquine) | Drug | ARM A, ARM B |
| ABT-263ARM A(Abiraterone with ABT-263) and ARM B(Abiraterone with both ABT-263 and Hydroxychloroquine) | Drug | ARM A, ARM B |
| HydroxychloroquineARM B(Abiraterone with both ABT-263 and Hydroxychloroquine) | Drug | ARM B |
Primary outcome
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.
7 secondary outcomes
Time to PSA Progression
Time frame: 5 years
Progression Free Survival
Time frame: 5 years
Measurable Tumor Response in Patients With Measurable Disease
Time frame: 5 years
Circulating Tumor Cells Pre-enrollment and During Therapy
Time frame: 5 years
Bcl-2 Family Protein Expression (Bcl-2, Bcl-XL, MCL-1) in Paraffin Blocks When Available by Immunohistochemistry
Time frame: 5 years
Biomarkers of Autophagy Modulation by EM; and LC3, and/or p62 by Immunoblotting in PBMC and Tumor Tissue When Available
Time frame: 5 years
Overall Survival
Time frame: 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert DiPaola, MD principal investigator
Rutgers, The State University of New Jersey
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Abiraterone, ABT-263 and Hydroxychloroquine in people with Prostate Cancer, run by Rutgers, The State University of New Jersey at 1 site 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 16 inclusion and 24 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: stopped early, as of the sponsor's last update on 4 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 May 2017.