Malignant Solid TumourPhase 1NCT01023737
Hydroxychloroquine + Vorinostat in Advanced Solid Tumors
A Phase 1 study testing Hydroxychloroquine and Vorinostat in people with Malignant Solid Tumour, run by The University of Texas Health Science Center at San Antonio at 1 site in United States.
Trial summary
This study is an open label non randomized study of hydroxychloroquine (HCQ) with histone deacetylase (HDAC) inhibitor Vorinostat in patients with advanced solid tumors to determine the maximum tolerated dose (MTD) and to evaluate the safety and antitumor activity of this drug combination. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Malignant Solid Tumour
- What is being tested?
- Hydroxychloroquine and Vorinostat
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2009to 8 Jan 2023
- 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 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients must be at least 16 years of age
- Patients must have a histologically confirmed non-hematological malignancy. Patients must have received and failed standard treatment for their malignancy; patients for whom no standard treatment is available will also be eligible.
- Patients must have an ECOG PS at 0, 1, or 2
- Patients must have adequate hematologic, renal and liver function (i.e. absolute Neutrophil count > 1000/mm3, platelets > 75,000/mm3); creatinine
- 2 times the upper limits of normal (ULN) total bilirubin ≤ 1.5 mg/dl, ALT and AST £ 3 times above the upper limits of the institutional norm ALT, AST can be < 5 times upper limits of normal if patients have hepatic involvement.
- Patients must be able to provide written informed consent.
Show all 13Show fewer
- Patients with the potential for pregnancy or impregnating their partner must agree to follow acceptable birth control methods to avoid conception. Women of childbearing potential must have a negative pregnancy test. The anti-proliferative activity of this experimental drug may be harmful to the developing fetus or nursing infant.
- Complete supportive and palliative care will continue to be provided to ameliorate signs and symptoms that were pre-existing or may arise while on study and which do not interfere with the objectives of the study.
- Tumor blocks available from previous surgery/biopsy.
- At the tumor specific expansion, only patients with metastatic colorectal and renal cell cancers will be enrolled. Patients with metastatic colorectal and renal cancer must have been treated and progressed or intolerant to standard care therapy.
- Patients with colorectal cancer must been treated in the past with Irinotecan and/or Oxaliplatin and/or AvastinIEGFR therapy or intolerant to these agents. No more than 4 lines of therapy permitted in the metastatic setting. Patients with colorectal cancer may enroll irrespective of K-Ras mutational status, although this will be documented.
- Patients with renal cell cancer must have been treated with a VEGF targeted therapy and/or mTOR inhibitor. No more than 4 lines of therapy permitted in the metastatic setting.
- Prior treatment with Vorinostat and HCQ are not permitted in each tumor type.
Who cannot join
- Patients with uncontrolled brain metastases.
- Due to risk of disease exacerbation patients with porphyria are not eligible.
- Due to risk of disease exacerbation patients with psoriasis are ineligible unless the disease is well controlled and they are under the care of a specialist for the disorder who agrees to monitor the patient for exacerbations.
- Patients with previously documented macular degeneration or diabetic retinopathy.
- Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for Nitrosoureas or Mitomycin C) prior to entering the study or those who have not recovered from adverse events to ≤ grade 1 due to agents administered more than 4 weeks earlier. For targeted therapies patients will need to clear for 5 half lives.
- Patients may not be receiving any other investigational agents.
Show all 15Show fewer
- Patients should not have taken valproic acid or another histone deacetylase inhibitor for at least 2 weeks prior to enrollment.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat or HCQ.
- 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.
- Major surgery or significant traumatic injury occurring within 21 days prior to treatment.
- Clinically significant hypercalcemia (including vomiting, dehydration and neurological symptoms).
- QTc > 500 ms at baseline (average of 3 determinations at 10 minutes interval).
- Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease. Patients with NJ, J or G tube will not be allowed to participate.
- Pregnant women are excluded from this study because SAHA has the potential for teratogenic or abortifacient effects
- Patients with known hepatitis B or C or HIV infection.
Trial locations and contacts
1 site in 1 country.
United States1 site
Cancer Therapy & Research Center University of Texas Health Science Center San Antonio
San Antonio, Texas, 78229
About this study
Official title: Inhibition of Autophagy in Solid Tumors: A Phase I Pharmacokinetic and Pharmacodynamic Study of Hydroxychloroquine in Combination With the HDAC Inhibitor Vorinostat for the Treatment of Patients With Advanced Solid Tumors With an Expansion Study in Advanced Renal and Colorectal Cancer
This study is an open label non randomized study of hydroxychloroquine (HCQ) with histone deacetylase (HDAC) inhibitor Vorinostat in patients with advanced solid tumors to determine the maximum tolerated dose (MTD) and to evaluate the safety and antitumor activity of this drug combination.
- Conditions
- Malignant Solid Tumour
- Being tested
- Hydroxychloroquine, Vorinostat
- Keywords
- Malignant Solid Tumor, Solid Tumor, Hydroxychloroquine, Vorinostat
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called HCQ
The HCQ study dose levels are defined as 400mg/day, 600mg/day, 800mg/day and 1000mg/day (oral dosing)during the phase I MTD determination. HCQ will be administered starting on Day 2 of Cycle 1 and will be continued daily thereafter until progression of disease or unacceptable toxicity develops.
VorinostatDrug
Also called Suberoylanilide Hydroxamic Acid
Oral administration of Vorinostat will be begin on Cycle 1 Day 1 at 300mg and will be continued daily thereafter until progression of disease or unacceptable toxicity develops.
| Study group | Role | What they receive |
|---|---|---|
| Hydroxychloroquine and Vorinostat | Experimental | Oral administration of Vorinostat will be begin on Cycle 1 Day 1 at 300mg and will be continued daily and HCQ will be administered starting on Day 2 of Cycle 1 and both will be continued daily thereafter until progression of disease or unacceptable toxicity develops. Receives: Drug: Hydroxychloroquine; Drug: Vorinostat |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD) of Hydroxychloroquine (HCQ) in combination with Vorinostat in patients with advanced solid tumors
Measured: 6+ months, MTD is assessed during the 1st cycle
Secondary outcomes (2)
To evaluate the safety and tolerability of HCQ in combination with Vorinostat in this patient population as determined by toxicity profile, incidence and rating according to NCI/CTC v3.0 criteria.
Measured: 1 year
To evaluate the antitumor activity of HCQ in combination with Vorinostat as determined by response rate and progression free survival (exploratory)
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 posted2 Dec 2009 (estimated)
- Study startNov 2009
- Primary completion5 Dec 2017
- Study completion8 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malignant Solid TumourStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- The University of Texas Health Science Center at San Antonio
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Sukeshi Patel Arora, MD, Principal investigator, The University of Texas Health Science Center at San Antonio
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01023737
- Sponsor's protocol ID
- IDD 08-52
- Other IDs
- 08-462H
- Status last verified
- Feb 2023
- First submitted
- 22 Jul 2009
- Last updated
- 13 Feb 2023
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inhibition of Autophagy in Solid Tumors: A Phase I Pharmacokinetic and Pharmacodynamic Study of Hydroxychloroquine in Combination With the HDAC Inhibitor Vorinostat for the Treatment of Patients With Advanced Solid Tumors With an Expansion Study in Advanced Renal and Colorectal Cancer
- ClinicalTrials.gov ID
- NCT01023737
- Acronym / sponsor ID
- IDD 08-52
- Conditions
- Malignant Solid Tumour
- Keywords
- Malignant Solid Tumor, Solid Tumor, Hydroxychloroquine, Vorinostat
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- The University of Texas Health Science Center at San AntonioUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Nov 2009
- Primary completion
- 5 Dec 2017 (actual)
- Study completion
- 8 Jan 2023 (actual)
- First posted
- 2 Dec 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.
This study is an open label non randomized study of hydroxychloroquine (HCQ) with histone deacetylase (HDAC) inhibitor Vorinostat in patients with advanced solid tumors to determine the maximum tolerated dose (MTD) and to evaluate the safety and antitumor activity of this drug combination.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Hydroxychloroquine and Vorinostat | Experimental | Drug: Hydroxychloroquine, Drug: VorinostatOral administration of Vorinostat will be begin on Cycle 1 Day 1 at 300mg and will be continued daily and HCQ will be administered starting on Day 2 of Cycle 1 and both will be continued daily thereafter until progression of disease or unacceptable toxicity develops. |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (13 listed)
- Patients must be at least 16 years of age
- Patients must have a histologically confirmed non-hematological malignancy. Patients must have received and failed standard treatment for their malignancy; patients for whom no standard treatment is available will also be eligible.
- Patients must have an ECOG PS at 0, 1, or 2
- Patients must have adequate hematologic, renal and liver function (i.e. absolute Neutrophil count > 1000/mm3, platelets > 75,000/mm3); creatinine
- Patients must be able to provide written informed consent.
Key exclusion criteria (15 listed)
- Patients with uncontrolled brain metastases.
- Due to risk of disease exacerbation patients with porphyria are not eligible.
- Due to risk of disease exacerbation patients with psoriasis are ineligible unless the disease is well controlled and they are under the care of a specialist for the disorder who agrees to monitor the patient for exacerbations.
- Patients with previously documented macular degeneration or diabetic retinopathy.
- Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for Nitrosoureas or Mitomycin C) prior to entering the study or those who have not recovered from adverse events to ≤ grade 1 due to agents administered more than 4 weeks earlier. For targeted therapies patients will need to clear for 5 half lives.
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 |
|---|---|---|
| HydroxychloroquineAlso: HCQThe HCQ study dose levels are defined as 400mg/day, 600mg/day, 800mg/day and 1000mg/day (oral dosing)during the phase I MTD determination. HCQ will be administered starting on Day 2 of Cycle 1 and will be continued daily thereafter until progression of disease or unacceptable toxicity develops. | Drug | Hydroxychloroquine and Vorinostat |
| VorinostatAlso: Suberoylanilide Hydroxamic AcidOral administration of Vorinostat will be begin on Cycle 1 Day 1 at 300mg and will be continued daily thereafter until progression of disease or unacceptable toxicity develops. | Drug | Hydroxychloroquine and Vorinostat |
Primary outcome
Maximum tolerated dose (MTD) of Hydroxychloroquine (HCQ) in combination with Vorinostat in patients with advanced solid tumors
Time frame: 6+ months, MTD is assessed during the 1st cycle
2 secondary outcomes
To evaluate the safety and tolerability of HCQ in combination with Vorinostat in this patient population as determined by toxicity profile, incidence and rating according to NCI/CTC v3.0 criteria.
Time frame: 1 year
To evaluate the antitumor activity of HCQ in combination with Vorinostat as determined by response rate and progression free survival (exploratory)
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 13 Feb 2023.
Related trials for Malignant Solid Tumour
Recruiting
Virtual Reality Intervention to Improve Psychological Symptom Burden for Cancer Patients Undergoing Treatment
Adjustment Disorder, Anxiety Disorder
Recruiting
Adding Spatially Fractionated Radiation Therapy to Standard Palliative Radiation for Improving Disease-Related Symptoms in Patients With Unresectable Solid Tumors
Metastatic Malignant Solid Neoplasm, Unresectable Malignant Solid Neoplasm
RecruitingObservational study
Solid Tumor Analysis for HLA Loss of Heterozygosity (LOH) and Apheresis for CAR T- Cell Manufacturing
Solid Tumor, Adult, Colorectal Cancer
Recruiting
Different Types of Massage Therapy to Reduce Anxiety During Chemotherapy Infusion in Patients With Cancer
Hematopoietic and Lymphatic System Neoplasm, Malignant Solid Neoplasm
RecruitingObservational study
Natural History and Biospecimen Acquisition for Children and Adults With Rare Solid Tumors
Malignant Solid Tumors, Other Neoplasms Solid Tumors
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.
Sukeshi Patel Arora, MD principal investigator
The University of Texas Health Science Center at San Antonio
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Hydroxychloroquine and Vorinostat in people with Malignant Solid Tumour, run by The University of Texas Health Science Center at San Antonio 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 13 inclusion and 15 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 13 Feb 2023. 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 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 Hydroxychloroquine (HCQ) in combination with Vorinostat in patients with advanced solid tumors (time frame: 6+ months, MTD is assessed during the 1st cycle). 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 13 Feb 2023.