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Inhibiting the Systemic Autophagic Syndrome - A Phase I/II Study of Hydroxychloroquine and Aldesleukin in Renal Cell Carcinoma Patients (RCC). A Cytokine Working Group (CWG) Study

Phase 1/Phase 2
18 Years
Open (Enrolling)
Metastatic Renal Cell Carcinoma

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Trial Information

Inhibiting the Systemic Autophagic Syndrome - A Phase I/II Study of Hydroxychloroquine and Aldesleukin in Renal Cell Carcinoma Patients (RCC). A Cytokine Working Group (CWG) Study

The rationale for combining the high dose bolus aldesleukin with hydroxychloroquine includes
potential positive interactions on the immune regulatory side, non-overlapping toxicities,
and potential for prolongation and increased number of responses based on murine studies
conducted at the University of Pittsburgh. This study is a multi-center phase II study
designed to estimate the efficacy of combination therapy of standard high dose bolus IL-2
and various doses of hydroxychloroquine therapy in metastatic RCC patients.

Inclusion Criteria:

- Histologically confirmed metastatic renal cell carcinoma with predominantly clear
cell histology.

- Have measurable disease by RECIST 1.1 criteria. For example, this would include tumor
in the lung, liver, and retroperitoneum. Bone disease is difficult to follow and
quantify and as a sole site would not be acceptable.

- Patients must be at least 4 weeks from radiation or surgery and recovered from all
ill effects.

- Age ≥18 years.

- Karnofsky Performance Status ≥80%.

- Adequate end organ function:

1. Hematologic: ANC ≥ 1000cells/uL, platelets ≥ 100,000/uL, hemoglobin ≥ 9g/dl
(pre transfusion values used for prognostic factor, can be transfused or use
recombinant erythropoietin growth factors but must not have active bleeding).

2. Liver: AST ≤ 2 x ULN (upper limit of normal), serum total bilirubin ≤ 2 x ULN
(except for patients with Gilbert's Syndrome).

3. Renal: serum creatinine ≤ 1.5 mg/dL or estimated creatinine clearance ≥
60ml/min using Cockcroft-Gault estimation using the formula per protocol.

4. Pulmonary: FEV1 ≥ 2.0 liters or ≥ 75% of predicted for height and age. (PFTs
are required for patients over 50 or with significant pulmonary or smoking
history defined as >20 pack years or history of COPD/emphysema).

5. Cardiac: No evidence of congestive heart failure, symptoms of coronary artery
disease, myocardial infarction less than one year prior to entry, serious
cardiac arrhythmias, or unstable angina. Patients who are over 40 or have had
previous cardiac disease will be required to have a negative or low probability
cardiac stress test for cardiac ischemia.

- Women should not be lactating and, if of childbearing age, have a negative pregnancy
test within two weeks of entry to the study.

- Appropriate contraception in both genders.

- The patient must be competent and have signed informed consent.

- CNS: No history of cerebrovascular accident, transient ischemic attacks, central
nervous system or brain metastases.

Exclusion Criteria:

- Patients who have received prior systemic therapy for metastatic RCC or have
previously received IL-2 are not eligible. Patients on HCQ in neoadjuvant protocols
or in the past for clinical indications ARE eligible.

- Concomitant second malignancy except for non-melanoma skin cancer, and non-invasive
cancer such as cervical CIS, superficial bladder cancer without local recurrence or
breast CIS.

- In patients with a prior history of invasive malignancy, less than five years in
complete remission.

- Positive serology for HIV, hepatitis B or hepatitis C.

- Significant co-morbid illness such as uncontrolled diabetes or active infection that
would preclude treatment on this regimen.

- Use of corticosteroids or other immunosuppression (if patient had been taking
steroids, at least 2 weeks must have passed since the last dose).

- History of inflammatory bowel disease or other serious autoimmune disease. (Not
including thyroiditis and rheumatoid arthritis). Patients already on
hydroxychloroquine for such disorders are not eligible.

- Patients with organ allografts.

- Uncontrolled hypertension (BP >150/100 mmHg).

- Proteinuria dipstick > 3+ or ≥ 2gm/24 hours.

- Urine protein:creatinine ratio ≥ 1.0 at screening.

- Major surgery, open biopsy, significant traumatic injury within 28 days of starting
treatment or anticipation of need for major surgical procedure during the course of
the study.

- Minor surgical procedures, fine needle aspirations or core biopsies within 7 days
prior to starting treatment. Central venous catheter placements are permitted.

- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 6 months prior to starting treatment.

- Serious, non-healing wound, ulcer, or bone fracture.

- History of tumor-related or other serious hemorrhage, bleeding diathesis, or
underlying coagulopathy.

- History of deep venous thrombosis, clinically significant peripheral vascular
disease, or other thrombotic event.

- Inability to comply with study and/or follow-up procedures.

- Individuals with known history of glucose 6 phosphate deficiency are excluded from
the trial (possible issue with HCQ tolerance).

- Patients with previously documented macular degeneration or diabetic retinopathy are
excluded from the trial.

- Baseline EKG with QTc > 470 msec (including subjects on medication). Subjects with
ventricular pacemaker for whom QT interval is not measurable will be eligible on a
case-by-case basis.

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Proportion of patients with metastatic RCC treated with IL-2 + HCQ at 1200mg/d who experience a clinical complete response.

Outcome Description:

Evaluation of target lesions: -Complete Response (CR): Disappearance of all target lesions Evaluation of non-target lesions -Complete Response (CR): Disappearance of all non-target lesions and normalization of tumor marker level

Outcome Time Frame:

up to 3 years to accrue and assess outcome

Safety Issue:


Principal Investigator

Michael T. Lotze, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Pittsburgh


United States: Food and Drug Administration

Study ID:

UPCI 11-080



Start Date:

March 2012

Completion Date:

March 2015

Related Keywords:

  • Metastatic Renal Cell Carcinoma
  • Carcinoma
  • Carcinoma, Renal Cell



University of Pittsburgh Cancer Institute/UPMC Cancer Centers Pittsburgh, Pennsylvania  15232