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Dose-finding Study of CAELYXTM and RAD001 in Patients With Advanced Solid Tumors

Phase 1
75 Years
Open (Enrolling)
Advanced Solid Tumors

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Trial Information

Dose-finding Study of CAELYXTM and RAD001 in Patients With Advanced Solid Tumors

mTOR inhibitors are a new class of targeted antitumor agents which showed interesting
antitumor activity in a variety of solid tumors, including prostate, soft tissue sarcomas ,
ovarian, endometrial, kidney, and breast cancer. They also exert an antiangiogenic effect
and are almost devoid of bone marrow toxicity as single agents which makes them suitable for
combination with cytotoxic drugs.

Anthracyclines are among the most used and effective cytotoxic agents, and in solid tumors
their indications include, among others, breast, ovary, endometrial, prostate cancer.
Liposomal Doxorubicin (CaelyxTM) could be an adequate replacement of doxorubicin to avoid
potential side effects such as cardiotoxicity, alopecia, GI toxicity.

Testing a combination regimen including mTOR inhibitors and anthracyclines in those tumors
which are known to be sensitive to both compounds is of high clinical interest and

Inclusion Criteria:

1. Histological/cytological diagnosis of solid tumors types for which treatment with an
anthracycline containing combination might be indicated.

2. Documented progressive disease prior to entry in the study

3. Though not a primary endpoint of this study when possible presence of measurable
and/or evaluable disease according to modified RECIST criteria
(histological/cytological confirmation of the neoplastic nature of a solitary lesion
is not required in this dose finding study). For patients with no measurable disease
(prostate and ovarian cancer) serum tumor marker (CA125 and PSA) is acceptable.

4. Preferentially ≤ 2 prior chemotherapies for advanced disease

5. An ECOG performance status of 0 or 1

6. Serum cholesterol <350 mg/dL and triglycerides <400 mg/dL

7. Adequate hematological, liver and renal function (hemoglobin ≥ 9g/dL, absolute
neutrophil count [ANC] ≥ 1.5 x 109/L; platelets ≥ 100 x 109/L, bilirubin ≤ UNL;
alkaline phosphatase ≤ 1.5 x UNL; AST, ALT ≤ UNL or 2.5 x UNL in case of liver
metastases; albumin ≥ 2.5 g/dL; creatinine ≤ UNL.

8. Male and female patients who are not surgically sterile or postmenopausal must agree
to use reliable methods of birth control for the duration of the study until 30 days
after the last dose of study drug

9. Able to understand and give written informed consent

10. Abdomen/Pelvis CT scans in the 4 weeks before planned treatment start

11. HBV/HCV testing in the 2 weeks before treatment start in specific categories of
patients with hepatitis B and C risk factors and in additional patients at the
discretion of the investigators.

Exclusion Criteria:

1. Prior Caelyx TM

2. Prior anthracycline therapy within last 12 months

3. Patients with endometrial ca. who received both chemotherapy and radiotherapy as
palliative treatment. Patients who received both chemotherapy and radiotherapy as
adjuvant treatment would be accepted provided that treatment has been completed more
than 2 years before inclusion; if treatments has been completed less than 2 years the
inclusion will be accepted only after Study Chair's approval.

4. Documented resistance to anthracycline therapy i.e progression whilst on therapy or
within 6 months after the end of therapy having achieved a response or stable disease
or after adjuvant therapy.

5. Prior cumulative dose of > 360 mg/m2 of doxorubicin or equivalent doxorubicin
cardiotoxic dose and/or LVEF (echo or MUGA) < 50%.

6. Known metastatic brain or meningeal tumors unless the patient is > 6 months from
definitive therapy, had a negative imaging study within 4 weeks of study entry, is
clinically stable with respect to the tumor at the time of study entry, and is not
receiving steroid therapy or taper

7. Prior therapy with rapamycin, mTOR inhibitors or tacrolimus

8. Prior anticancer treatment (chemotherapy, radiotherapy, hormonal, immunotherapy,
biological response modifiers, signal transduction inhibitors, etc) within 4 weeks
prior to the first dose of RAD001; the interval is ≥ 2 weeks for signal transduction
inhibitors with a half-life known to be <24 hours, and is ≥ 6 weeks for nitrosourea
or mitomycin. The following exceptions are allowed:

- hormonal therapy (e.g., Megace) for appetite stimulation

- nasal, ophthalmic, and topical glucocorticoid preparations

- a stable dose of corticosteroids for at least two weeks

- low dose maintenance steroid therapy for other conditions

- physiologic hormone replacement therapy (e.g., thyroid supplementation for
thyroid deficiency or oral replacement glucocorticoid therapy for adrenal

9. Pre-existing malabsorption syndrome, irritable bowel syndrome or other clinical
situation which could affect oral absorption

10. Ongoing toxicity associated with prior anticancer therapy (except peripheral
neuropathy of ≤ grade 1 by NCI toxicity criteria and alopecia)

11. Another primary malignancy within the past three years (except for non-melanoma skin
cancer and cervical carcinoma in situ)

12. Known Grade 3 or 4 hypersensitivity to macrolide antibiotics (e.g., clarithromycin,
erythromycin, azithromycin)

13. Significant uncontrolled cardiovascular disease

14. Active infection requiring systemic therapy

15. Known HIV infection

16. Inadequate recovery from any prior surgical procedure or having undergone any major
surgical procedure within 2 weeks prior to the first dose of RAD001. Patients having
undergone recent placement of a central venous access port will be considered
eligible if they have recovered

17. Presence of any other life-threatening illness or organ system dysfunction which, in
the opinion of the Investigator, would either compromise the patient's safety or
interfere with evaluating the safety of the study drug

Type of Study:


Study Design:

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

Outcome Measure:

Maximum Tolerated Dose (MTD) and Recommended Dose (RD)

Outcome Description:

The Maximum Tolerated Dose (MTD) is defined as the dose in which 2 of 3 or 2 of 6 patients experience a Dose Limiting Toxicity (DLT).The Recommended Dose (RD) is defined as one dose level below the MTD.

Outcome Time Frame:

4 weeks

Safety Issue:


Principal Investigator

Cristiana Sessa, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Istituto Oncologico della Svizzera Italiana- Ospedale s.Giovanni - 6500 Bellinzona, Switzerland


Italy: The Italian Medicines Agency

Study ID:




Start Date:

October 2007

Completion Date:

December 2011

Related Keywords:

  • Advanced Solid Tumors
  • Neoplasms