Study of Hydroxychloroquine and Aldesleukin in Renal Cell Carcinoma Patients (RCC)

NCT01550367 | Completed Phase 1 Results DMC

• 1 other identifier: UPCI 11-080
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 7

Brief Summary

The main goal of the research study is to determine whether treating renal cell cancer patients with the study drug, hydroxychloroquine, along with IL-2, a standard treatment of kidney cancer that has spread to other parts of the body, can make the cancer easier to kill and eliminate. Another goal is to see how the study drug affects the body's immune cells which fight cancer cells.

Conditions

Metastatic Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (3)

• Clinical Response - IL-2 Combined With Hydroxychloroquine (HCQ) at Either 1,200 mg/d or 600 mg/d) (All Patients)

  Clinical Response: per RECIST v1.1: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (target or non-target) with reduction in short axis to \<10 mm. Partial Response (PR): ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Progressive Disease (PD):≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.

  Up to 3 years

• Clinical Response - IL-2 Combined With Hydroxychloroquine (HCQ) at 1,200 mg/d

  Clinical Response: per RECIST v1.1: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (target or non-target) with reduction in short axis to \<10 mm. Partial Response (PR): ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Progressive Disease (PD):≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.

  Up to 3 years

• Clinical Response - IL-2 Combined With Hydroxychloroquine (HCQ) at 600 mg/d

  Clinical Response: per RECIST v1.1: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (target or non-target) with reduction in short axis to \<10 mm. Partial Response (PR): ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Progressive Disease (PD):≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.

  Up to 3 years

Secondary Outcomes (18)

• Overall Survival (OS)

  Up to 3 years

• Progression-free Survival (PFS)

  Up to 3 years

• Number of Doses of IL-2 + HCQ

  Up to 3 years

• Frequency of Grade III and Grade IV Toxicities

  Up to 3 years

• Worst Grade of Adverse Event Experienced

  Up to 3 years

Study Arms (1)

Hydroxychloroquine + IL-2

EXPERIMENTAL

One course of treatment (84 days) will consist of high dose (600,000 IU/kg) bolus IL-2 administered intravenously every 8 hours on days 1-5 and 15-19 (maximum 14 doses/5 days of administration) and hydroxychloroquine (HCQ) orally started two weeks prior to IL-2 infusions and continued while able to take oral medication for up to 3 courses.

Drug: Hydroxychloroquine; Drug: IL-2

Interventions

Hydroxychloroquine DRUG

Continuous oral administration (at 600 mg/d) will be initiated prior to the first dose (day -14) given 14 days prior to initiation of the first dose of IL-2 and then daily or twice a day throughout all three treatment courses.

Also known as: Plaquenil

Hydroxychloroquine + IL-2

IL-2 DRUG

600,000 IU/kg IV bolus q 8 hrs x days 1-5 and 15-19 (maximum 28 doses - 14 per 5 day cycle) of each 84-day course

Also known as: Aldesleukin

Hydroxychloroquine + IL-2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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).
• Liver: AST ≤ 2 x ULN (upper limit of normal), serum total bilirubin ≤ 2 x ULN (except for patients with Gilbert's Syndrome).
• Renal: serum creatinine ≤ 1.5 mg/dL or estimated creatinine clearance ≥ 60ml/min using Cockcroft-Gault estimation using the formula per protocol.
• 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).
• 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.

You may not qualify if:

• Patients who have previously received IL-2 are NOT eligible. Patients on HCQ in neoadjuvant protocols or in the past for clinical indications ARE eligible, as are patients who have previously received CTLA-4 and/or PD-1/PD-L1 antibodies.
• 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.

Sponsors & Collaborators

• Leonard Appleman: lead
• Prometheus Laboratories: collaborator

Study Sites (7)

Loyola University Chicago

Maywood, Illinois, 60153, United States

Location

Indiana University Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Dartmouth-Hitchcock Medical Center

Hanover, New Hampshire, 03755, United States

Location

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Providence Health & Services

Portland, Oregon, 97213, United States

Location

University of Pittsburgh Cancer Institute / UPMC CancerCenter

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Hydroxychloroquine; Interleukin-2; aldesleukin

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Results Point of Contact

• Title: Barbara Stadterman, MPH, MCCR, Regulatory Supervisor, CRS
• Organization: UPMC Hillman Cancer Center

stadtermanbm@upmc.edu

412-647-5554

Study Officials

• Leonard J Appleman, MD, PhD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: February 29, 2012
• First Posted: March 12, 2012
• Study Start: March 1, 2012
• Primary Completion: February 6, 2018
• Study Completion: February 1, 2019
• Last Updated: January 2, 2020
• Results First Posted: September 25, 2019

Record last verified: 2019-12

Locations

US (7)