Melanoma (Skin)Early Phase 1NCT00962845
Hydroxychloroquine in Patients With Stage III or Stage IV Melanoma That Can Be Removed by Surgery
A Early Phase 1 study testing hydroxychloroquine in people with Melanoma (Skin), run by Rutgers, The State University of New Jersey at 1 site in United States.
Trial summary
RATIONALE: Studying samples of blood, tumor tissue, and skin in the laboratory from patients with melanoma receiving hydroxychloroquine may help doctors understand the effect of hydroxychloroquine on biomarkers. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Melanoma (Skin)
- What is being tested?
- hydroxychloroquine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2010to 30 May 2013
- Phase
- Early 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 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed melanoma
- Stage III or IV disease
- Has ≥ 2 resectable tumors OR tumor large enough to undergo pre-treatment core needle biopsy
- Must be a candidate for curative or palliative surgical resection of disease
- Brain metastases allowed provided they were previously treated and have been stable for > 2 weeks
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Absolute granulocyte count > 1,500/mm³
- Platelet count > 100,000/mm³
- SGOT and SGPT < 2.5 times upper limit of normal (ULN)
- Negative pregnancy test
- Fertile patients must use effective contraception
- No history of any social or medical condition that, in the opinion of the investigator, may interfere with the patient's ability to comply with the study or pose additional or unacceptable risk to the patient
- No concurrent serious systemic disorder that, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient's ability to complete the study
- No active clinically significant infection requiring antibiotics
- No hypertension that cannot be controlled by medication (i.e., diastolic blood pressure > 100 mm Hg despite optimal medical therapy)
- No pre-existing thyroid abnormality with thyroid-stimulating hormone that cannot be maintained in the normal range with medication
- No known HIV positivity
- No psoriasis or porphyria
- No known hypersensitivity to 4-aminoquinoline compounds
- No retinal or visual field changes from prior 4-aminoquinoline compound use
- No known G-6P deficiency
- No known gastrointestinal pathology that would interfere with drug bioavailability
- No known prior hypersensitivity to hydroxychloroquine or any of its components
- No clinically significant bleeding or clotting disorder that would preclude curative or palliative surgery
PRIOR CONCURRENT THERAPY:
- Recovered from prior therapy
- More than 2 weeks since prior cytotoxic or biologic agents (6 weeks for mitomycin or nitrosoureas)
- At least 2 weeks since prior surgery, radiotherapy, hormonal therapy, or other drug therapy for melanoma
- No concurrent treatment for rheumatoid arthritis or systemic lupus erythematosus
- No concurrent disease-modifying anti-rheumatic drugs
- No concurrent hydroxychloroquine for treatment or prophylaxis of malaria
- No concurrent aurothioglucose or antimalarial agents
- No other concurrent chemotherapy, immunotherapy, hormonal therapy, radiotherapy, or surgery for cancer
- No other concurrent investigational agents
Trial locations and contacts
1 site in 1 country.
United States1 site
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903
About this study
Official title: A Phase 0 Trial of Hydroxychloroquine, an Inhibitor of Autophagy, in Patients With Stage III or IV Resectable Melanoma
RATIONALE: Studying samples of blood, tumor tissue, and skin in the laboratory from patients with melanoma receiving hydroxychloroquine may help doctors understand the effect of hydroxychloroquine on biomarkers.
PURPOSE: This early phase I trial is studying hydroxychloroquine in patients with stage III or stage IV melanoma that can be removed by surgery.
Read the detailed description
OBJECTIVES:
Primary
- To characterize the effects of hydroxychloroquine (HCQ) on the modulation of markers of autophagy, as measured by p62, Beclin1, LC3, and GRp170 expression, in pre- and post-treatment tumor biopsy samples, skin samples, and peripheral blood mononuclear cell samples from patients with stage III or IV melanoma undergoing palliative or curative surgery.
Secondary
- To determine whether the steady-state plasma concentration of HCQ correlates with observed trends in induced markers of autophagy.
- To determine the potential mechanisms of antitumor effect of HCQ, as measured by a reduction in tumor cell proliferation (Ki-67 and mitotic rate) or an increase in apoptosis (activated caspase-3 and TUNEL assays) in melanoma specimens.
OUTLINE: Patients receive oral hydroxychloroquine twice daily for 14 days in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery.
Blood, tumor tissue, and skin samples are collected for pharmacokinetic and correlative laboratory studies. Expression of p62, Beclin1, LC3, and GRp170 (autophagy markers) is analyzed.
- Conditions
- Melanoma (Skin)
- Being tested
- hydroxychloroquine
- Keywords
- stage III melanoma, stage IV melanoma
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
200 mg twice daily in the first ten patients. If the first ten patients tolerate this dosage schedule (200 mg bid) without significant side effects (Grade 3 or greater gastrointestinal upset, skin toxicity, myopathy or any visual disturbances whatsoever), the second ten patients will be enrolled at a dose of 400 mg bid
| Study group | Role | What they receive |
|---|---|---|
| Hydroxychloroquine | Experimental | Patients must have tumor accessible for pre-treatment biopsy (see 5.1.2). Patients will be enrolled on the trial, undergo biopsy of their tumors if no banked tumor is available, and then begin an oral dose of HCQ at the dose of 200 mg twice daily. At the end of two weeks the patients will undergo resection of their tumors. HCQ will be given to the patients up to the day of the operation but not resumed postoperatively. Receives: Drug: hydroxychloroquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Modulation of markers of autophagy by hydroxychloroquine (HCQ), as measured by p62, Beclin1, LC3, and GRp170 expression
Measured: 1 year
Secondary outcomes (2)
Correlation of steady-state plasma concentration of HCQ with observed trends in induced markers of autophagy
Measured: 1 year
Potential mechanisms of antitumor effect of HCQ, as measured by a reduction in tumor cell proliferation or an increase in apoptosis
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2009 (estimated)
- Study startSep 2010
- Primary completion30 May 2013
- Study completion30 May 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Melanoma (Skin)Studies 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rutgers, The State University of New Jersey
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Rutgers Cancer Institute of New Jersey
- Responsible party
- Sponsor
- Investigators
- Janice M. Mehnert, MD, Principal investigator, Rutgers Cancer Institute of New Jersey
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00962845
- Sponsor's protocol ID
- 0220090117
- Other IDs
- P30CA072720, CDR0000648156, NCI-2011-03324, 090901
- Status last verified
- Sep 2022
- First submitted
- 19 Aug 2009
- Last updated
- 7 Sep 2022
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 0 Trial of Hydroxychloroquine, an Inhibitor of Autophagy, in Patients With Stage III or IV Resectable Melanoma
- ClinicalTrials.gov ID
- NCT00962845
- Acronym / sponsor ID
- 0220090117
- Conditions
- Melanoma (Skin)
- Keywords
- stage III melanoma, stage IV melanoma
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Rutgers, The State University of New JerseyUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), Rutgers Cancer Institute of New Jersey
- Study start
- Sep 2010
- Primary completion
- 30 May 2013 (actual)
- Study completion
- 30 May 2013 (actual)
- First posted
- 20 Aug 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Studying samples of blood, tumor tissue, and skin in the laboratory from patients with melanoma receiving hydroxychloroquine may help doctors understand the effect of hydroxychloroquine on biomarkers.
PURPOSE: This early phase I trial is studying hydroxychloroquine in patients with stage III or stage IV melanoma that can be removed by surgery.
Detailed description
OBJECTIVES:
Primary
- To characterize the effects of hydroxychloroquine (HCQ) on the modulation of markers of autophagy, as measured by p62, Beclin1, LC3, and GRp170 expression, in pre- and post-treatment tumor biopsy samples, skin samples, and peripheral blood mononuclear cell samples from patients with stage III or IV melanoma undergoing palliative or curative surgery.
Secondary
- To determine whether the steady-state plasma concentration of HCQ correlates with observed trends in induced markers of autophagy.
- To determine the potential mechanisms of antitumor effect of HCQ, as measured by a reduction in tumor cell proliferation (Ki-67 and mitotic rate) or an increase in apoptosis (activated caspase-3 and TUNEL assays) in melanoma specimens.
OUTLINE: Patients receive oral hydroxychloroquine twice daily for 14 days in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery.
Blood, tumor tissue, and skin samples are collected for pharmacokinetic and correlative laboratory studies. Expression of p62, Beclin1, LC3, and GRp170 (autophagy markers) is analyzed.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Hydroxychloroquine | Experimental | Drug: hydroxychloroquinePatients must have tumor accessible for pre-treatment biopsy (see 5.1.2). Patients will be enrolled on the trial, undergo biopsy of their tumors if no banked tumor is available, and then begin an oral dose of HCQ at the dose of 200 mg twice daily. At the end of two weeks the patients will undergo resection of their tumors. HCQ will be given to the patients up to the day of the operation but not resumed postoperatively. |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| hydroxychloroquine200 mg twice daily in the first ten patients. If the first ten patients tolerate this dosage schedule (200 mg bid) without significant side effects (Grade 3 or greater gastrointestinal upset, skin toxicity, myopathy or any visual disturbances whatsoever), the second ten patients will be enrolled at a dose of 400 mg bid | Drug | Hydroxychloroquine |
Primary outcome
Modulation of markers of autophagy by hydroxychloroquine (HCQ), as measured by p62, Beclin1, LC3, and GRp170 expression
Time frame: 1 year
2 secondary outcomes
Correlation of steady-state plasma concentration of HCQ with observed trends in induced markers of autophagy
Time frame: 1 year
Potential mechanisms of antitumor effect of HCQ, as measured by a reduction in tumor cell proliferation or an increase in apoptosis
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Sep 2022.
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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.
Janice M. Mehnert, MD principal investigator
Rutgers Cancer Institute 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 Early Phase 1 study testing hydroxychloroquine in people with Melanoma (Skin), 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?
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 7 Sep 2022. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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?
Modulation of markers of autophagy by hydroxychloroquine (HCQ), as measured by p62, Beclin1, LC3, and GRp170 expression (time frame: 1 year). 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 7 Sep 2022.