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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


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Malignant Solid Tumour

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Trial Information

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


Inclusion Criteria:



- 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.

- 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.

Exclusion Criteria:

- 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.

- 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 SAHA 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.

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Maximum tolerated dose (MTD) of Hydroxychloroquine (HCQ) in combination with Vorinostat in patients with advanced solid tumors

Outcome Time Frame:

6+ months, MTD is assessed during the 1st cycle

Safety Issue:

Yes

Principal Investigator

Devalingam Mahalingam, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Texas Health Science Center San Antonio

Authority:

United States: Institutional Review Board

Study ID:

IDD 08-52

NCT ID:

NCT01023737

Start Date:

November 2009

Completion Date:

November 2013

Related Keywords:

  • Malignant Solid Tumour
  • Malignant Solid Tumor
  • Solid Tumor
  • Hydroxychloroquine
  • Vorinostat
  • Neoplasms

Name

Location

Cancer Therapy & Research Center University of Texas Health Science Center San AntonioSan Antonio, Texas  78229