Know Cancer

forgot password

Targeting Autophagy for the Treatment of TSC and LAM: a Phase I Trial of Hydroxychloroquine and Sirolimus

Phase 1
18 Years
85 Years
Open (Enrolling)

Thank you

Trial Information

Targeting Autophagy for the Treatment of TSC and LAM: a Phase I Trial of Hydroxychloroquine and Sirolimus

This will be a phase I dose escalation study of the combination of sirolimus (2 mg adjusted
to keep trough levels between 5-15 ng/ml) and hydroxychloroquine (200 mg or 400 mg) taken
orally daily for 6 months. The study is to be conducted at 2 sites. Up to 18 adult women
with LAM will be enrolled, and each recruiting site will recruit between 8-12 subjects. The
protocol will use the following eligibility criteria.

Inclusion Criteria:

- Female age 18 or older

- Ability to give informed consent

- Diagnosis of LAM as defined as typical cystic change on CT plus:

- biopsy or cytology of any tissue demonstrating LAM

- angiomyolipoma, chylothorax, lymphangioleiomyoma, or tuberous sclerosis

- serum VEGFD greater or equal to 800pg/ml

- Post-bronchodilator FEV1 equal or less than 80% of predicted or DLCO equal equal or
less than 70% of predicted, or RV > 120% of predicted at baseline

- Women of childbearing potential must agree to use 2 forms of barrier contraception
during and for 8 weeks after the last dose of medication.

Exclusion Criteria:

- History of intolerance of mTOR inhibitors

- History of intolerance to hydroxychloroquine

- History of severe psoriasis

- History of porphyria cutanea tarda

- Uncontrolled intercurrent illness

- Pregnant, breast feeding, or plan to become pregnant in the next year

- Inadequate contraception

- Significant hematological or hepatic abnormalities

- Use of an investigational drug within 30 days of study start

- Inability to attend scheduled clinic visits

- Inability to perform PFTs

- Creatinine > 2.5mg/dL

- Recent pneumothorax within 8 weeks of screening

- History of malignancy in the last 2 years other than basal cell skin cancer

- Use of estrogen containing medication within 30 days of screening

- Abnormal G6PD levels at baseline

- Preexisting maculopathy or retinopathy

- Preexisting myopathy

- Currently taking doxycycline, metformin, lupron, simvastatin

- Unable to undergo CT or MRI

- History of seizure within last year

- Hepatitis B, C, HIV positive serology

- Use of alternative medical therapies for LAM for at least 6 weeks prior to study

- History of myocardial infarct, angina, or stroke related to atherosclerosis

- History of cardiomyopathy

- Previous lung transplant

- Surgery (involving entry into a body cavity or requiring 3 or more stitches) within 2
months of initiation of study drug

- Uncontrolled cholesterol > 350mg/dL, triglycerides > 400mg/dL

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

safety of everolimus and hydroxychloroquine

Outcome Description:

We will conduct a two-center phase I trial of sirolimus (mTOR inhibitor) in combination with hydroxychloroquine (autophagy inhibitor 200-400mg) administered daily for 24 weeks. Eligible subjects will receive sirolimus at an initial dose of 2mg followed by dose adjustment to keep sirolimus trough levels between 5-15ng/ml consistent with the effective dose in the MILES trial. In addition to sirolimus subjects will receive hydroxychloroquine at 200 mg daily or twice a day for 6 months, depending on time of enrollment into the study, following a standard phase I dose escalation design. All adverse events will be captured.

Outcome Time Frame:

4 years

Safety Issue:


Principal Investigator

Elizabeth P Henske, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Brigham and Women's Hospital


United States: Federal Government

Study ID:




Start Date:

September 2012

Completion Date:

June 2016

Related Keywords:

  • Lymphangioleiomyomatosis
  • LAM
  • TSC
  • lymphangioleiomyomatosis
  • Lymphangioleiomyomatosis



Brigham and Women's HospitalBoston, Massachusetts  02115