Paclitaxel and Carboplatin or Bleomycin Sulfate, Etoposide Phosphate, and Cisplatin in Treating Patients With Advanced or Recurrent Sex Cord-Ovarian Stromal Tumors

Brief Title

Paclitaxel and Carboplatin or Bleomycin Sulfate, Etoposide Phosphate, and Cisplatin in Treating Patients With Advanced or Recurrent Sex Cord-Ovarian Stromal Tumors

Official Title

A Randomized Phase II Trial of Paclitaxel and Carboplatin vs. Bleomycin, Etoposide, and Cisplatin for Newly Diagnosed Advanced Stage and Recurrent Chemonaive Sex Cord-Stromal Tumors of the Ovary

Brief Summary

      This randomized phase II trial studies paclitaxel and carboplatin to see how well they work
      compared with bleomycin sulfate, etoposide phosphate, and cisplatin in treating patients with
      sex cord-ovarian stromal tumors that have spread to other places in the body and usually
      cannot be cured or controlled with treatment (advanced) or has returned (recurrent). Drugs
      used in chemotherapy work in different ways to stop the growth of tumor cells, either by
      killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving
      more than one drug (combination chemotherapy) may kill more tumor cells. It is not yet known
      which chemotherapy regimen is more effective in treating sex cord-ovarian stromal tumors.

Detailed Description


      I. To assess the activity of paclitaxel and carboplatin with respect to progression free
      survival (using bleomycin, etoposide, and cisplatin [BEP] as a reference) for newly diagnosed
      advanced or recurrent chemonaive ovarian sex cord-stromal tumors.


      I. To estimate the toxicity of paclitaxel and carboplatin, and bleomycin, etoposide, and
      cisplatin in this patient population.

      II. To estimate overall survival for paclitaxel and carboplatin relative to that of BEP.

      III. To evaluate response rate in the subset of patients with measurable disease.


      I. To collect fixed and/or frozen tumor tissue for future translational research studies.

      II. To explore the utility of inhibin A and inhibin B as prognostic and predictive biomarkers
      for ovarian sex cord-stromal tumors and to examine changes in these markers with treatment.

      OUTLINE: Patients are randomized to 1 of 2 treatment arms.

      ARM I: Patients receive paclitaxel intravenously (IV) over 3 hours and carboplatin IV over 1
      hour on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease
      progression or unacceptable toxicity.

      ARM II: Patients receive bleomycin sulfate IV on day 1 and etoposide phosphate* IV over 1
      hour and cisplatin IV over 30 minutes on days 1-5. Treatment repeats every 21 days for 4
      courses in the absence of disease progression or unacceptable toxicity.

      NOTE: *Patients who have received prior radiotherapy receive etoposide phosphate on days 1-4.

      After completion of study therapy, patients are followed up every 3 months for 2 years, every
      6 months for 3 years, and then annually thereafter.

Study Phase

Phase 2

Study Type


Primary Outcome

Progression-free survival (PFS)

Secondary Outcome

 Tumor response rate


Ovarian Granulosa Cell Tumor


Bleomycin Sulfate

Study Arms / Comparison Groups

 Arm I (paclitaxel, carboplatin)
Description:  Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

February 8, 2010

Primary Completion Date

January 2, 2024

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with histologically confirmed ovarian stromal tumor [granulosa cell tumor,
             ganulosa cell-theca cell tumor, Sertoli-Leydig cell tumor (androblastoma), steroid
             (lipid) cell tumor, gynandroblastoma, unclassified sex cord-stromal tumor, sex cord
             tumor with annular tubules]

          -  Patients must have newly diagnosed, stage IIA ? IV disease and must be entered within
             eight weeks from surgery; they may have either measurable residual disease by Response
             Evaluation Criteria In Solid Tumors (RECIST) criteria, or they may have no measurable
             residual disease; OR, they must have biopsy-proven recurrent disease of any stage and
             have never received cytotoxic chemotherapy

          -  Patients must have a Gynecologic Oncology Group (GOG) performance grade of 0, 1, or 2

          -  Patients of childbearing potential must have a negative serum pregnancy test and must
             agree to practice an effective means of birth control

          -  Patients in the measureable disease cohort must have at least one ?target lesion? to
             be used to assess response on this protocol as defined by RECIST 1.1; tumors within a
             previously irradiated field will be designated as ?non-target? lesions unless
             progression is documented or a biopsy is obtained to confirm persistence at least 90
             days following completion of radiation therapy

          -  Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl, equivalent to
             Common Terminology Criteria for Adverse Events (CTCAE) grade 1

          -  Platelet greater than or equal to 100,000/mcl

          -  Creatinine no greater than the institutional upper limits of normal

          -  Bilirubin less than or equal to 1.5 x upper limit of normal (ULN) (CTCAE grade 1)

          -  Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) less
             than or equal to 3.0 x ULN (CTCAE grade 1)

          -  Alkaline phosphatase less than or equal to 2.5 x ULN (CTCAE grade 1)

          -  Neuropathy (sensory and motor) less than or equal to CTCAE grade 1

          -  No signs of clinically significant hearing loss

          -  Patients must have signed an approved informed consent and authorization permitting
             release of personal health information

          -  Patients must have pulmonary function sufficient to receive bleomycin, with normal
             lung expansion, absence of crackles on auscultation, and normal carbon monoxide
             diffusion (DLCO), defined as greater than 80% predicted

          -  Patients with a history of hypersensitivity reactions to prior chemotherapy
             administered for previous cancer diagnoses are eligible to participate in the study,
             unless the hypersensitivity reaction consisted of anaphylaxis not amenable to

          -  Recovery from effects of recent surgery, radiotherapy, or chemotherapy

               -  Patients must be entered within 8 weeks after surgery performed for either 1)
                  initial diagnosis, staging, and/or cytoreduction, or 2) (if done) management of
                  recurrent disease in a chemonaive patient

               -  Any hormonal therapy directed at the malignant tumor must be discontinued at
                  least one week prior to registration; continuation of hormone replacement therapy
                  is permitted

        Exclusion Criteria:

          -  Patients who have received any prior cytotoxic chemotherapy or biologics for sex
             cord-stromal tumors (SCSTs)

          -  Patients with apparent stage I disease who have not undergone a staging procedure

          -  Patients with a history of other invasive malignancies, with the exception of
             non-melanoma skin cancer, are excluded if there is any evidence of other malignancy
             being present within the last five years

          -  Woman who are pregnant or breastfeeding

          -  Patients with medical history or conditions not otherwise previously specified which
             in the opinion of the investigator should exclude participation in this study; the
             investigator can consult the study chair or study co-chairs for uncertainty in this




18 Years - N/A

Accepts Healthy Volunteers



Jubilee Brown, , 

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID


Secondary IDs


Responsible Party


Study Sponsor

Gynecologic Oncology Group


 National Cancer Institute (NCI)

Study Sponsor

Jubilee Brown, Principal Investigator, NRG Oncology

Verification Date

March 2019