Metastatic Clear Cell Renal Cell CarcinomaPhase 1/2NCT01510119
Autophagy Inhibition to Augment Mammilian Target of Rapamycin (mTOR) Inhibition: A Phase I/II Trial of RAD001 and Hydroxychloroquine (HCQ) in Patients With Previously Treated Renal Cell Carcinoma
A Phase 1/2 study testing Hydroxychloroquine and RAD001 in people with Metastatic Clear Cell Renal Cell Carcinoma, run by Abramson Cancer Center at Penn Medicine at 3 sites in United States.
Trial summary
This is an open labeled phase I dose escalation study of hydroxychloroquine (HCQ) and RAD001 in patients with advanced renal cell carcinoma followed by a Phase II trial of RAD001 with HCQ. The target population are patients with one to three prior treatments for advanced renal cell carcinoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Clear Cell Renal Cell Carcinoma
- What is being tested?
- Hydroxychloroquine and RAD001
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 3 sitesUnited States
- Study dates
- Sep 2011to 5 Jan 2017
- Phase
- Phase 1/2
- 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
- 1 Histological evidence of metastatic renal cell carcinoma that has been previously treated with 1-3 prior regimens
- 2 Phase I only, any number of prior regimens with evidence of progressive disease
- 3 Patients must have at least one measurable site of disease according to RECIST criteria that has not been previously irradiated. If the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation
- 4 Age 18 years
- 5 Eastern Cooperative Oncology Group (ECOG) performance status £
- 6 Adequate bone marrow function as shown by: absolute neutrophil count (ANC) 1.5 x 109/L, Platelets 100 x 109/L, Hb 9 g/dL
Show all 11Show fewer
- 7 Adequate liver function as shown by:
- 8 Serum bilirubin 1.5 x upper limit of normal
- 9 ALT and aspartate aminotransferase (AST) 2.5x upper limit of normal ( 5x upper limit of normal in patients with liver metastases)
- 10 international normalized ratio (INR) and PTT 1.5. (Anticoagulation is allowed if target INR 1.5 on a stable dose of warfarin or on a stable dose of anticoagulant for 2 weeks at time of randomization.) Adequate renal function: serum creatinine 2.0 x upper limit of normal or Creatinine Clearance 60 .11 Fasting serum cholesterol 300 mg/dL OR 7.75 mmol/L AND fasting triglycerides 2.5 x upper limit of normal . NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication.
- 12 Signed informed consent
Who cannot join
- .1. Patients currently receiving anticancer therapy or who have received anticancer therapy within 4 weeks of the start of study drug (including chemotherapy, radiation therapy, antibody based therapy, etc.). To prevent explosive disease progression associated with angiogenic rebound from impacting the results of this study, patients who have received prior antiangiogenic therapy in the form of a small molecule multikinase inhibitor or bevacizumab must be off prior therapy for 1 week and have antiangiogenic therapy-associated adverse events (AEs) resolve to grade 2 before starting study treatment.
- 2 Patients, who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery or patients that may require major surgery during the course of the study
- 3 Prior treatment with any investigational drug within the preceding 4 weeks .4 Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent. Topical or inhaled corticosteroids are allowed.
- 5 Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period
- 6 Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases
- 7 Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin, Stage I resected melanoma, ductal carcinoma in situ, squamous cell carcinoma of the skin, resected, basal cell carcinoma, indolent prostate cancer
Show all 21Show fewer
- 8 Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
- 9 Symptomatic congestive heart failure of New York heart Association Class III or IV
- 10 Unstable angina pectoris, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease
- 11 Severely impaired lung function with a previously documented spirometry and diffusing capacity of lung for carbon monoxide that is 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest on room air
- 12 Uncontrolled diabetes as defined by fasting serum glucose 1.5 x ULN
- 13 Active (acute or chronic) or uncontrolled severe infections
- 14 Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis
- 15 A known history of HIV seropositivity as reported by the patient
- 16 Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
- 17 Patients with an active, bleeding diathesis
- 18 Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. If barrier contraceptives are being used, these must be continued throughout the trial by both sexes. Hormonal contraceptives are not acceptable as a sole method of contraception. (Women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to administration of RAD001)
- 19 Patients who have received prior treatment with an mammilian target of rapamycin (mTOR) inhibitor (sirolimus, temsirolimus, everolimus).(Phase I prior mTOR inhibitor allowed)
- 20 Patients with a known hypersensitivity to RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus) or to its excipients
- 21 History of noncompliance to medical regimens
- 22 Patients unwilling to or unable to comply with the protocol .23 A detailed assessment of Hepatitis B/C medical history and risk factors must be done at screening for all patients. HBV DNA and HCV RNA polymerase chain reaction testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior HBV/HCV infection.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of Medicine and Dentistry of New Jersey
New Brunswick, New Jersey
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
University of Pittsburgh, Hillman Cancer Center
Pittsburgh, Pennsylvania
About this study
This is an open labeled phase I dose escalation study of hydroxychloroquine (HCQ) and RAD001 in patients with advanced renal cell carcinoma followed by a Phase II trial of RAD001 with HCQ. The target population are patients with one to three prior treatments for advanced renal cell carcinoma. In the phase I portion a traditional 3+3 design will be used to determine the maximal tolerated dose and/or recommended phase II dose for HCQ in combination with RAD001 po 10 mg/day.
Read the detailed description
This protocol describes a multicenter phase I/II trial of RAD001 in combination with hydroxychloroquine (HCQ) (phase I anticipated n=6-12) with a 35 patient phase II trial in patients with previously treated (1-3 prior regimens) advanced renal cell carcinoma. The preclinical rationale for this combination is extensive, the safety of HCQ combination strategies has been established, and effective autophagy pharmacodynamics (PD), and pharmacokinetics (PK) assays are available to guide development. The practical advantage of combination with HCQ is that this drug is off patent, commercially available, and is investigational new drug (IND) exempt. The institutions involved have combined 11 clinical protocols open for accrual involving HCQ, so regulatory approval will be rapid. There are no competing HCQ protocols for advanced renal cell carcinoma. As described in the sample size justification we are setting a high threshold to consider RAD001 + HCQ active since there are many competitors and other potential rational combinations. The 35 patient sample size is designed as a 2 stage phase II trial that will guide the go/no-go decision regarding the conduct of a followup randomized study to definitively prove efficacy. The primary (6 month PFS) and secondary outcomes (response rate, toxicity rates, correlative endpoints) will be analyzed for the entire group, and for patient populations stratified by number of prior therapies. The phase I portion of this trial is anticipated to be short, based on our experience from other HCQ trials. As a safety measure we have included intermediate dose levels which will only be used if there are Dose Limiting Toxicities (DLTs). Since we have seen responses at lower doses of HCQ in other trials, and because frequently over months HCQ dose is lowered from Maximum Tolerated Dose (MTD) doses in many trials because of nausea and anorexia, we would like to have some data on renal cell patients treated at the lower dose levels. If there is activity demonstrated at lower doses, this would be informative for dose modification decisions in patients treated on the dose expansion. The patient population for this trial, including the phase I dose escalation portion is advanced renal cell carcinoma with 1-3 prior treatments.
- Being tested
- Hydroxychloroquine, RAD001
- Medical subject headings
- Clear-cell metastatic renal cell carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called HCQ
RAD001Drug
Also called Everolimus, Afinitor
| Study group | Role | What they receive |
|---|---|---|
| Intervention - Dose Level 1 | Experimental | RAD001 given 10mg/daily by mouth and 400mg hydroxychloroquine twice daily by mouth. Cycle 1 will include 1 week run-in of RAD001. Following this, both RAD001 and hydroxychloroquine given without interruption. Cycle 1 duration is 35 days; all subsequent cycles are 28 days. RAD001 and hydroxychloroquine continuously administered until progression of disease or unacceptable toxicity. Receives: Drug: Hydroxychloroquine; Drug: RAD001 |
| Intervention - Dose Level 2 Phase 2 | Experimental | RAD001 given 10mg/daily by mouth and 600mg hydroxychloroquine twice daily by mouth. Cycle 1 will include 1 week run-in of RAD001. Following this, both RAD001 and hydroxychloroquine given without interruption. Cycle 1 duration is 35 days; all subsequent cycles are 28 days. RAD001 and hydroxychloroquine continuously administered until progression of disease or unacceptable toxicity. Receives: Drug: Hydroxychloroquine; Drug: RAD001 |
What is being measured
The primary outcome is the main question the study is designed to answer.
PFS
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2012 (estimated)
- Study startSep 2011
- Primary completion4 Apr 2016
- Study completion5 Jan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Clear Cell Renal Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Abramson Cancer Center at Penn MedicineThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Abramson Cancer Center at Penn Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- University of Pittsburgh, Rutgers Cancer Institute of New Jersey
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01510119
- Sponsor's protocol ID
- UPCC 07811
- Status last verified
- Apr 2020
- First submitted
- 11 Jan 2012
- Last updated
- 24 Apr 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Autophagy Inhibition to Augment Mammilian Target of Rapamycin (mTOR) Inhibition: A Phase I/II Trial of RAD001 and Hydroxychloroquine (HCQ) in Patients With Previously Treated Renal Cell Carcinoma
- ClinicalTrials.gov ID
- NCT01510119
- Acronym / sponsor ID
- UPCC 07811
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Abramson Cancer Center at Penn MedicineUniversity, hospital or other
- Collaborators
- University of Pittsburgh, Rutgers Cancer Institute of New Jersey
- Study start
- Sep 2011 (actual)
- Primary completion
- 4 Apr 2016 (actual)
- Study completion
- 5 Jan 2017 (actual)
- First posted
- 13 Jan 2012 (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 is an open labeled phase I dose escalation study of hydroxychloroquine (HCQ) and RAD001 in patients with advanced renal cell carcinoma followed by a Phase II trial of RAD001 with HCQ. The target population are patients with one to three prior treatments for advanced renal cell carcinoma. In the phase I portion a traditional 3+3 design will be used to determine the maximal tolerated dose and/or recommended phase II dose for HCQ in combination with RAD001 po 10 mg/day.
Detailed description
This protocol describes a multicenter phase I/II trial of RAD001 in combination with hydroxychloroquine (HCQ) (phase I anticipated n=6-12) with a 35 patient phase II trial in patients with previously treated (1-3 prior regimens) advanced renal cell carcinoma. The preclinical rationale for this combination is extensive, the safety of HCQ combination strategies has been established, and effective autophagy pharmacodynamics (PD), and pharmacokinetics (PK) assays are available to guide development. The practical advantage of combination with HCQ is that this drug is off patent, commercially available, and is investigational new drug (IND) exempt. The institutions involved have combined 11 clinical protocols open for accrual involving HCQ, so regulatory approval will be rapid. There are no competing HCQ protocols for advanced renal cell carcinoma. As described in the sample size justification we are setting a high threshold to consider RAD001 + HCQ active since there are many competitors and other potential rational combinations. The 35 patient sample size is designed as a 2 stage phase II trial that will guide the go/no-go decision regarding the conduct of a followup randomized study to definitively prove efficacy. The primary (6 month PFS) and secondary outcomes (response rate, toxicity rates, correlative endpoints) will be analyzed for the entire group, and for patient populations stratified by number of prior therapies. The phase I portion of this trial is anticipated to be short, based on our experience from other HCQ trials. As a safety measure we have included intermediate dose levels which will only be used if there are Dose Limiting Toxicities (DLTs). Since we have seen responses at lower doses of HCQ in other trials, and because frequently over months HCQ dose is lowered from Maximum Tolerated Dose (MTD) doses in many trials because of nausea and anorexia, we would like to have some data on renal cell patients treated at the lower dose levels. If there is activity demonstrated at lower doses, this would be informative for dose modification decisions in patients treated on the dose expansion. The patient population for this trial, including the phase I dose escalation portion is advanced renal cell carcinoma with 1-3 prior treatments.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention - Dose Level 1 | Experimental | Drug: Hydroxychloroquine, Drug: RAD001RAD001 given 10mg/daily by mouth and 400mg hydroxychloroquine twice daily by mouth. Cycle 1 will include 1 week run-in of RAD001. Following this, both RAD001 and hydroxychloroquine given without interruption. Cycle 1 duration is 35 days; all subsequent cycles are 28 days. RAD001 and hydroxychloroquine continuously administered until progression of disease or unacceptable toxicity. |
| Intervention - Dose Level 2 Phase 2 | Experimental | Drug: Hydroxychloroquine, Drug: RAD001RAD001 given 10mg/daily by mouth and 600mg hydroxychloroquine twice daily by mouth. Cycle 1 will include 1 week run-in of RAD001. Following this, both RAD001 and hydroxychloroquine given without interruption. Cycle 1 duration is 35 days; all subsequent cycles are 28 days. RAD001 and hydroxychloroquine continuously administered until progression of disease or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 1 Histological evidence of metastatic renal cell carcinoma that has been previously treated with 1-3 prior regimens
- 2 Phase I only, any number of prior regimens with evidence of progressive disease
- 3 Patients must have at least one measurable site of disease according to RECIST criteria that has not been previously irradiated. If the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation
- 4 Age 18 years
- 5 Eastern Cooperative Oncology Group (ECOG) performance status £
Key exclusion criteria (21 listed)
- .1. Patients currently receiving anticancer therapy or who have received anticancer therapy within 4 weeks of the start of study drug (including chemotherapy, radiation therapy, antibody based therapy, etc.). To prevent explosive disease progression associated with angiogenic rebound from impacting the results of this study, patients who have received prior antiangiogenic therapy in the form of a small molecule multikinase inhibitor or bevacizumab must be off prior therapy for 1 week and have antiangiogenic therapy-associated adverse events (AEs) resolve to grade 2 before starting study treatment.
- 2 Patients, who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery or patients that may require major surgery during the course of the study
- 3 Prior treatment with any investigational drug within the preceding 4 weeks .4 Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent. Topical or inhaled corticosteroids are allowed.
- 5 Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period
- 6 Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases
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: HCQ | Drug | Intervention - Dose Level 1, Intervention - Dose Level 2 Phase 2 |
| RAD001Also: Everolimus, Afinitor | Drug | Intervention - Dose Level 1, Intervention - Dose Level 2 Phase 2 |
Primary outcome
PFS
Time frame: 6 months
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 24 Apr 2020.
Related trials for Metastatic Clear Cell Renal Cell Carcinoma
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1/2
Pazopanib Hydrochloride and Bevacizumab in Treating Patients With Previously Untreated Metastatic Kidney Cancer
Clear Cell Renal Cell Carcinoma, Stage IV Renal Cell Cancer
RecruitingPhase 2
Phase II Trial of Combination Anti-PD-1 and Aldesleukin for Metastatic Melanoma and Renal Cell Carcinoma
Metastatic Melanoma, Advanced Locoregional Melanoma
Active, not recruitingPhase 1
P-MUC1C-ALLO1 Allogeneic CAR-T Cells in the Treatment of Subjects With Advanced or Metastatic Solid Tumors
Breast Cancer, Ovarian Cancer
RecruitingPhase 1
Open-Label Phase 1/2 Study of NEO-811 in Subjects With Locally Advanced or Metastatic Non-Resectable Clear Cell Renal Cell Carcinoma
Clear Cell Renal Cell Carcinoma, Renal Cell Carcinoma
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.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Hydroxychloroquine and RAD001 in people with Metastatic Clear Cell Renal Cell Carcinoma, run by Abramson Cancer Center at Penn Medicine at 3 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 11 inclusion and 21 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 24 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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 combined 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.
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?
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?
PFS (time frame: 6 months). 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 24 Apr 2020.