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Phase 1A/B Study of Combination Carboplatin, Paclitaxel and Ridaforolimus in Patients With Solid, Endometrial, and Ovarian Cancers

Phase 1
18 Years
Open (Enrolling)
Endometrial Cancer, Ovarian Cancer

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Trial Information

Phase 1A/B Study of Combination Carboplatin, Paclitaxel and Ridaforolimus in Patients With Solid, Endometrial, and Ovarian Cancers

This is a phase 1A/1B study. Phase 1A is designed to determine the maximal tolerated dose
(MTD) and toxicity of ridaforolimus in combination with paclitaxel and carboplatin in
patients with advanced or recurrent solid tumors. The MTD determined in this study will be
the recommended dose to study in the phase 1B or in future phase 2 trials.

Inclusion Criteria:

- Must have measurable disease or evaluable disease. Measurable disease is defined as
at least one lesion that can be accurately measured in at least one dimension
(longest dimension to be recorded). Each lesion must be a minimum size of 10 mm by CT
scan (CT scan slice thickness no greater than 5 mm), 10 mm caliper measurement by
clinical exam or 20 mm by chest X-ray. Lymph node must be ≥ 15 mm in short axis when
assessed by CT scan. Evaluable disease is disease evident on imaging that does not
meet Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1, however,
meets tumor marker evaluation, e.g., Gynecologic Cancer Intergroup (GCIG) criteria.
Notes: i) If the patient's only disease is confined to a solitary lesion, its
neoplastic nature must be confirmed by histology or cytology unless it is accompanied
by GCIG criteria or can be clearly be shown as new disease when compared to prior
imaging. ii) Disease in a previously irradiated field is acceptable as the only site
of measurable disease only if there has been clear progression since completion of

- Age > 18 years and competent to give informed consent.

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2 and a life
expectancy of at least 60 days.

- Patients must have adequate: Bone marrow function: Absolute neutrophil count (ANC)
greater than or equal to 1,500/ul, equivalent to Common Toxicity Criteria (CTCAE
v4.0) grade 1. Platelets greater than or equal to 100,000/ul.; Renal function:
creatinine less than or equal to 1.5 x institutional upper limit normal (ULN), CTCAE
v4.0 grade 1.; Hepatic function: Bilirubin less than or equal to 1.5 x ULN (CTCAE
v4.0 grade 1). serum glutamic oxaloacetic transaminase (SGOT) and alkaline
phosphatase less than or equal to 2.5 x ULN (CTCAE v4.0 grade 1).; Neurologic
function: Neuropathy (sensory and motor) less than or equal to CTCAE v4.0 grade 1.;
No chemotherapy, radiotherapy, biologic, hormonal, or investigational drug therapy
within 28 days prior to start of treatment on study.

- Women of childbearing potential (WOCBP) must have a negative serum pregnancy test
prior to the study entry and be practicing an effective method of birth control
during the course of the study, in a manner such that risk of failure is minimized.
Prior to study enrollment, WOCBP must be advised of the importance of avoiding
pregnancy during trial participation and the potential risk factors for an
intentional pregnancy.

- Phase 1A - Additional criteria applicable to phase 1A

- Must have pathologically confirmed solid cancer that is locally advanced or
metastatic cancer.

- Patient's physician believes that the cancer is advanced, recurrent or
metastatic and not curable by local measures (i.e., surgery, radiation, other

- Patient's physician believes the patient may potentially benefit from this
combination of therapy.

- Patients may have had up to three (3) prior cytotoxic chemotherapeutic regimens
including prior treatment with carboplatin and paclitaxel. Chemotherapy drug
changes and modifications made for reasons other than progression are not
considered a separate regimen. Examples would be drug changes for toxicity or
consolidation chemotherapy after adjuvant treatment. Patients may have received
any number of prior non-cytotoxic regimens such as monoclonal antibodies,
cytokines, signal transduction inhibitors, or hormonal therapy. Previous
radiation therapy is allowed.

- Phase 1B - Endometrial: Additional Inclusion Criteria

- Epithelial endometrial cancer. (i.e. carcinosarcoma, leiomyosarcoma, and
endometrial stromal sarcoma are excluded).

- May have had up to one prior chemotherapy for endometrial cancer. Prior taxane
or platinum therapy is allowed as long as it was received either as adjuvant
therapy or if there were a response to prior therapy and at least 6 months have
elapsed since platinum treatment. Radiation sensitizing chemotherapy will not
count as a prior regimen.

- Must have measurable disease

- Phase 1B - Ovarian: Additional Inclusion Criteria

- Recurrent epithelial ovarian cancer (no stromal or germ cell ovarian cancers)

- Platinum-sensitive defined as a recurrence at least 6 months (180 days) after
the last day of primary adjuvant chemotherapy. Patients may have been retreated
with a salvage line of chemotherapy but there must be a platinum-free interval
of 6 or more months.

- Two (2) or less prior therapies including adjuvant chemotherapy

- Measurable or evaluable disease

Exclusion Criteria:

- An upper gastrointestinal or other condition that would impair swallowing or
absorption of oral medication

- Any serious illness or medical condition that would not permit the patient to be
managed according to the protocol, including, but not limited to, any the following:

- History of significant neurologic or psychiatric disorder (e.g., uncontrolled
psychiatric disorders) that would impair the ability to obtain consent or limit
compliance with study requirement

- Active uncontrolled or serious infection

- Active peptic ulcer disease

- Patients who have the following cardiac conditions: Uncontrolled angina or
myocardial infarction with the past six months; Diagnosed or suspected
congenital long QT syndrome; Any history of clinically significant ventricular
arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or
Torsades de pointes); Prolonged QTc interval on pre-entry electrocardiogram (>
450 msec) on both the Fridericia and Bazett's correction

- Uncontrolled hypertension defined as systolic greater than 180 and diastolic greater
than 100.

- History of other invasive malignancies in the last 3 years, with the exception of
non-melanoma skin cancer, unless they have had no evidence of recurrence from that
cancer for last two years.

- Serum creatinine >1.5 times the institutional upper limits of normal

- Patients taking certain concomitant medications (see below). Patients can enroll on
protocol if they stop these medications and a wash-out period of ≥14 days, unless
otherwise noted, is done prior to starting ridaforolimus.

- There must be at least 14 days since prior (and no current expectations to receive)
CYP3A4 inhibitors including, but not limited to, any of the following: Azole
antifungals ( i.e., ketoconazole, itraconazole, miconazole, fluconazole); HIV
protease inhibitors (i.e., indinavir, saquinavir, ritonavir, atazanavir, nelfinavir);
Clarithromycin; Verapamil; Erythromycin; Delavirdine; Diltiazem; Nefazodone;

- There must be at least 14 days since prior (and no current expectations to receive)
CYP3A4 inducers including, but not limited to, any of the following

- Rifampin

- Phenytoin

- Rifabutin

- St.John's wort

- Carbamazepine

- Efavirenz

- Phenobarbital

- Tipranavir

- Full dose anticoagulation with warfarin (coumadin) or other vitamin K dependent
anticoagulant. Low-dose prophylactic warfarin (i.e. 1mg per day port prophylaxis) is
allowable. Low molecular heparin (e.g., danaparoid, dalteparin, tinzaparin,
enoxaparin) is allowable if patient has been established on therapy.

- Have received an estimated dose of radiation therapy to >35% of the bone marrow.

- Patients previously exposed to mTOR inhibitors are permitted in phase 1A but not
allowed in phase 1B.

- History of grade 3 hypersensitivity to paclitaxel. However, if after prior
hypersensitivity the patient was subsequently successfully rechallenged without
incident, the patient may be eligible at investigator's discretion.

- Known hypersensitivity to the study drug ridaforolimus or its components.
Ridaforolimus should be administered with caution to patients known to be
hypersensitive to macrolide antibiotics, Tween80 (polysorbate 80), or any other
excipient in the product formulation.

- Significant lipid abnormalities: Serum cholesterol > 350mg/dL; Triglycerides >

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Part 1A - Maximum Tolerated Dose (MTD)

Outcome Description:

To determine the maximal tolerated dose of oral ridaforolimus in combination with paclitaxel and carboplatin during the first cycle of treatment.

Outcome Time Frame:

Average of six months

Safety Issue:


Principal Investigator

Robert Wenham, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

H. Lee Moffitt Cancer Center and Research Institute


United States: Food and Drug Administration

Study ID:




Start Date:

June 2011

Completion Date:

December 2013

Related Keywords:

  • Endometrial Cancer
  • Ovarian Cancer
  • metastatic
  • recurrent
  • Solid Cancer
  • Endometrial Neoplasms
  • Ovarian Neoplasms
  • Adenoma



H. Lee Moffitt Cancer Center and Research Institute Tampa, Florida  33612