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A Phase 1 Study of Carboplatin and Gemcitabine Chemotherapy and Stereotactic Body Radiosurgery for the Palliative Treatment of Persistent or Recurrent Gynecologic Cancer

Phase 1
19 Years
Open (Enrolling)
Leydig Cell Tumor, Ovarian Sarcoma, Ovarian Stromal Cancer, Pseudomyxoma Peritonei, Recurrent Cervical Cancer, Recurrent Endometrial Carcinoma, Recurrent Fallopian Tube Cancer, Recurrent Ovarian Epithelial Cancer, Recurrent Ovarian Germ Cell Tumor, Recurrent Primary Peritoneal Cavity Cancer, Recurrent Uterine Sarcoma, Recurrent Vaginal Cancer, Recurrent Vulvar Cancer

Thank you

Trial Information

A Phase 1 Study of Carboplatin and Gemcitabine Chemotherapy and Stereotactic Body Radiosurgery for the Palliative Treatment of Persistent or Recurrent Gynecologic Cancer


I. Determine maximum tolerated carboplatin/gemcitabine dose administered with SBRT as
measured by < 30‐day acute toxicity defined by Common Terminology Criteria for Adverse
Events (CTCAE) v4.0.


I. Off-study SBRT target local control assessment: 6-week post-trial fludeoxyglucose F 18
(18F-FDG) positron emission tomography (PET)/computed tomography (CT) or other imaging
response by European Organisation for Research and Treatment of Cancer (EORTC) PET criteria
as listed and National Cancer Institute (NCI) guidelines.

II. Off-treatment late toxicity assessment: record 3-month and 6-month radiation-related
toxicity defined by CTCAE v4.0.

III. Off‐study global clinical benefit assessment: 6‐month post-therapy clinical benefit
(defined as percentage of patients who had complete, partial, or stable disease for at least
6 months).


I. Associate pretherapy tumor biopsy ribonucleotide reductase (R1, R2, p53R2), Tip60 and
Poly(ADP‐ribose) polymerase 1/2 expression with 6‐week therapy response.

OUTLINE: This is a dose-escalation study of carboplatin and gemcitabine hydrochloride.

Patients also receive carboplatin intravenously (IV) over 30 minutes and gemcitabine
hydrochloride IV over 30 minutes on day 1 and undergo SBRT on days 2-4.

After completion of study treatment, patients are followed up every 3 months for 2 years,
every 6 months for 1 year, and then yearly for 2 years.

Inclusion Criteria:

- Patient has diagnosis of a persistent or recurrent gynecologic cancer

- Patient age is > 18 years.

- Patient must have at least one abdominopelvic measurable site of disease as defined
by 9.1.3;. A treatment planning 18F‐FDG positron emission tomography and computed
tomography scan (PET/CT; whole body) may be used to complement assessment, & if done
must be completed prior to first dose of carboplatin / gemcitabine and within 35 days
of first day of SBRT. There MUST BE no more than four (4) intended radiosurgical
target lesions. An individual (one of up to four) radiosurgical target lesion MUST
NOT EXCEED a volume of no greater than 160 cubic centimeters (cc).

- No prior cryosurgery or radiofrequency ablation in SBRT‐target lesion. Patients with
prior cryoablation and radiofrequency ablation are excluded as these treatments are
designed to destroy tissue with freezing or heat. Radiation treatments given by SBRT
may not work biologically or may cause excessive tissue injury in patients who have
had prior cryoablation and radiofrequency ablation.

- Patient has no major medical illnesses or psychiatric illnesses:

1. New York Heart Association (NYHA) class 3 or 4 congestive heart failure;

2. unstable angina pectoris;

3. symptomatic cardiac arrhythmia;

4. hypertension with diastolic blood pressure greater than 110 mmHg;

5. pulmonary disease consisting of dyspnea at rest requiring oxygen

6. renal function impairment (defined here as baseline serum creatinine >2.0

7. psychiatric illness/social situations that would limit compliance.

- Patient must have no known brain metastases. These patients are excluded from this
clinical trial because of their poor prognosis and because they often develop
progressive neurological dysfunction that would confound neurological and other
adverse event evaluation.

- Patient must demonstrate adequate organ function (< 35 days from enrollment):

- Bone marrow: absolute neutrophil count (ANC) ≥ 1500/mcl, platelets ≥ 100,000,
hemoglobin ≥ 10 mg/dL.

- Renal function: creatinine ≤ 2.0 mg/dL.

- Hepatic function: bilirubin ≤ 1.5X institutional upper limit of normal (ULN);
AST, ALT, alkaline phosphatase ≤ 2.5X ULN

- Patient MUST have had prior chemotherapy or radiation for a gynecologic cancer.
Patient is > 28 days from previous treatment (chemotherapy or radiation) and
toxicities related to the previous treatment must have resolved to grade 1 or

- Patient has Gynecologic Oncology Group performance status score of 0 or 1.

- Patient is able to give study‐specific informed consent

Exclusion Criteria:

- Any patient NOT meeting the above criteria

- Any patient with active connective tissue disease such as lupus or dermatomyositis is
excluded; patients with active connective tissue disease are at an excessive risk of
organ function‐impairing fibrosis

- Any patient with active Crohn's disease or active ulcerative colitis is excluded;
patients having these conditions are at an excessive risk of organ function‐impairing

- Any patient with known anaphylaxis to carboplatin or gemcitabine is excluded

- Pregnant women are excluded from this study because radiation has the potential for
teratogenic or abortifacient effects; screening beta‐human chorionic gonadotropin
(hcg) levels (urine or blood) and diagnostic tests will be used to determine
eligibility in women of childbearing potential; women of child‐bearing potential and
men must agree to use adequate contraception (hormonal or barrier method of birth
control; abstinence) prior to study entry and for the duration of study
participation; should a woman become pregnant or suspect she is pregnant while
participating in this study, she should inform her treating physician immediately;
these potential risks may also apply to carboplatin/gemcitabine chemotherapy agents
used in this study

- Human immunodeficiency virus (HIV)‐positive patients on combination antiretroviral
therapy are ineligible because of the potential for pharmacokinetic interactions with
carboplatin or gemcitabine; in addition, patients known to be HIV‐positive patient
are excluded due to an increased risk of lethal infections when treated with
marrow‐suppressive therapy such as carboplatin/gemcitabine; HIV testing is not
mandatory for eligibility evaluation

- Due to a perceived increased risk to transplanted organ for lethal dysfunction or
lethal infection, patients with visceral organ transplants are not eligible

- Patients with other active non‐gynecologic invasive malignancies are excluded;
patients with other invasive malignancies who had (or have) cancer present within the
last two years are excluded

Type of Study:


Study Design:

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

Outcome Measure:

Rate of acute grade 3-5 toxicities following carboplatin/gemcitabine hydrochloride and SBRT treatment graded based on CTCAE, version 4.0

Outcome Description:

A modified Fibonacci design used during the dose-finding portion of this study. When =< 1 out of 6 patients enter at highest next dose level below the maximum tolerated dose (MTD), this is the recommended phase 2 dose. At least 6 patients must be entered at the recommended phase 2 dose.

Outcome Time Frame:

Within 30 days of completing treatment

Safety Issue:


Principal Investigator

Robert DeBernardo, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center


United States: Institutional Review Board

Study ID:




Start Date:

May 2012

Completion Date:

Related Keywords:

  • Leydig Cell Tumor
  • Ovarian Sarcoma
  • Ovarian Stromal Cancer
  • Pseudomyxoma Peritonei
  • Recurrent Cervical Cancer
  • Recurrent Endometrial Carcinoma
  • Recurrent Fallopian Tube Cancer
  • Recurrent Ovarian Epithelial Cancer
  • Recurrent Ovarian Germ Cell Tumor
  • Recurrent Primary Peritoneal Cavity Cancer
  • Recurrent Uterine Sarcoma
  • Recurrent Vaginal Cancer
  • Recurrent Vulvar Cancer
  • Carcinoma
  • Uterine Cervical Neoplasms
  • Leydig Cell Tumor
  • Pseudomyxoma Peritonei
  • Vaginal Neoplasms
  • Vulvar Neoplasms
  • Peritoneal Neoplasms
  • Fallopian Tube Neoplasms
  • Neoplasms, Germ Cell and Embryonal
  • Adenoma
  • Germinoma
  • Ovarian Neoplasms
  • Endometrial Neoplasms
  • Neoplasms, Glandular and Epithelial
  • Sarcoma



Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center Cleveland, Ohio  44106-5065