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Docetaxel, Trabectedin, and G-CSF or Pegfilgrastim in Treating Patients With Recurrent or Persistent Ovarian Epithelial Cancer, Primary Peritoneal Cavity Cancer, or Fallopian Tube Cancer

A Phase II Evaluation of Docetaxel (NSC #628503) Plus Trabectedin (Yondelis®), R279741, IND # 101018) With Growth Factor Support in the Third-Line Treatment of Recurrent or Persistent Ovarian, Fallopian Tube or Primary Peritoneal Cancer

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00569673
Enrollment
71
Registered
2007-12-07
Start date
2008-03-31
Completion date
Unknown
Last updated
2018-07-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Fallopian Tube Cancer, Ovarian Cancer, Primary Peritoneal Cavity Cancer

Keywords

recurrent ovarian epithelial cancer, fallopian tube cancer, primary peritoneal cavity cancer

Brief summary

RATIONALE: Drugs used in chemotherapy, such as docetaxel and trabectedin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Colony-stimulating factors, such as G-CSF and pegfilgrastim, may help the immune system recover from the side effects of chemotherapy. Giving combination chemotherapy together with G-CSF or pegfilgrastim may kill more tumor cells. PURPOSE: This phase II trial is studying the side effects and how well giving docetaxel and trabectedin together with G-CSF or pegfilgrastim works in treating patients with recurrent or persistent ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cavity cancer.

Detailed description

OBJECTIVES: Primary * To estimate the antitumor activity of docetaxel plus trabectedin in patients with persistent or recurrent ovarian epithelial, fallopian tube, or primary peritoneal cavity cancer primarily through the frequency of objective tumor responses. * To determine the nature and degree of toxicity of docetaxel plus trabectedin in this cohort of patients. Secondary * To estimate the progression-free survival and overall survival of patients treated with docetaxel and trabectedin. OUTLINE: Patients receive docetaxel IV over 1 hour and trabectedin IV over 3 hours on day 1. Patients also receive pegfilgrastim subcutaneously (SC) on day 1 OR filgrastim (G-CSF) IV over 15-30 minutes or SC once daily beginning on day 1 and continuing until blood counts recover. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 3 years.

Interventions

BIOLOGICALfilgrastim
BIOLOGICALpegfilgrastim
DRUGdocetaxel
DRUGtrabectedin

Sponsors

National Cancer Institute (NCI)
CollaboratorNIH
Gynecologic Oncology Group
Lead SponsorNETWORK

Study design

Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
FEMALE
Age
18 Years to 120 Years
Healthy volunteers
No

Inclusion criteria

DISEASE CHARACTERISTICS: * Histologically confirmed ovarian epithelial, fallopian tube, or primary peritoneal cavity carcinoma * Recurrent or persistent disease * Measurable disease, defined as at least 1 lesion that can be accurately measured in at least 1 dimension (longest dimension to be recorded) ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan * Must have at least 1 target lesion to be used to assess response on this protocol as defined by RECIST criteria * 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 * Must have had 1 prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound and the initial treatment may have included high-dose therapy, consolidation, or extended therapy administered after surgical or non-surgical assessment * Patients are allowed, but not required to receive, 2 additional cytotoxic regimens for management of recurrent or persistent disease with no more than 1 non-platinum, non-taxane regimen * Patients who have received only 1 prior cytotoxic regimen (platinum-based regimen for management of primary disease), must meet 1 of the following criteria: * Platinum-free interval of \< 12 months * Progressed during platinum-based therapy * Persistent disease after a platinum-based therapy * Not eligible for a higher priority GOG protocol (i.e., any active GOG Phase III protocol for the same patient population) PATIENT CHARACTERISTICS: * GOG performance status (PS) 0-2 or after receiving 1 prior treatment regimen (GOG PS 0-1 after receiving 2 or more prior regimens) * Platelet count ≥ 100,000/mm³ * ANC count ≥ 1,500/mm³ * Hemoglobin \> 9 g/dL * Creatinine ≤ 1.5 times upper limit normal (ULN) * AST and ALT ≤ 2.5 times ULN * CPK normal * Bilirubin or direct bilirubin normal * Alkaline phosphatase normal * Neuropathy (sensory and motor) ≤ grade 1 * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No active infection requiring antibiotics (except for uncomplicated UTI) * No other invasive malignancy within the past 5 years, except nonmelanoma skin cancer * No known active liver disease or hepatitis * Willing and able to have a central venous catheter PRIOR CONCURRENT THERAPY: * See Disease Characteristics * Recovered from effects of recent surgery, radiotherapy, or chemotherapy * At least 1 week since prior hormonal therapy directed at the malignant tumor * Continuation of hormone replacement therapy allowed * At least 3 weeks since other prior therapy, including biological and immunological therapy directed at the tumor * Chimeric or human or humanized monoclonal antibodies must be discontinued for at least 6 weeks prior to study entry * No investigational therapy within the past 30 days * No prior therapy with docetaxel and/or trabectedin * No radiation to more than 25% of marrow-bearing areas * No prior cancer treatment that contraindicates protocol therapy

Design outcomes

Primary

MeasureTime frameDescription
Objective Tumor Responseevery other cycle for the first 6 months; then every 3 months thereafter (up to 5 years)Response is measured according to Response Evaluation Criteria in Solid Tumors Criteria (RECIST v 1.0): Complete Response (CR) is disappearance of all target and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Partial Response (PR) is at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD. Disease Progression is at least a 20% increase in the sum of LD of target lesions taking as references the smallest sum LD or the appearance of new lesions within 8 weeks of study entry. Stable Disease is any condition not meeting the above criteria. Indeterminate is defined as having no repeat tumor assessments following initiation of study therapy6
Number of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0Prior to each cycle and 30 days after the last cycle (average of 5 months)

Secondary

MeasureTime frame
Duration of Progression-free Survival and Overall Survivalup to 5 years

Countries

United States

Participant flow

Participants by arm

ArmCount
Docetaxel Plus Trabectedin
Docetaxel 60 mg/m2 IV over 1 hour followed by trabectedin (YONDELISµ, R279741) formerly referred to as, ET-743) 1.1 mg/m2 over 3 hours with Filgrastim (G-CSF, NSC #614629), Pegfilgrastim (G-CSF, NSC #725961) or Sargramostim (GM-CSF, NSC #613795) every 3 weeks (one cycle) until disease progression or adverse effects prohibit further therapy.
71
Total71

Baseline characteristics

CharacteristicDocetaxel Plus Trabectedin
Age, Customized
40-49 years
10 participants
Age, Customized
50-59 years
28 participants
Age, Customized
60-69 years
25 participants
Age, Customized
70-79 years
7 participants
Age, Customized
80-89 years
1 participants
Age, Customized59.3 years
STANDARD_DEVIATION 9.2
Cell Type
Adenocarcinoma, Unspecified
7 participants
Cell Type
Clear Cell Carcinoma
3 participants
Cell Type
Endometrioid Adenocarcinoma
6 participants
Cell Type
Mixed Epithelial Carcinoma
2 participants
Cell Type
Serous Adenocarcinoma
53 participants
Region of Enrollment
United States
71 participants
Sex: Female, Male
Female
71 Participants
Sex: Female, Male
Male
0 Participants

Adverse events

Event typeEG000
affected / at risk
deaths
Total, all-cause mortality
— / —
other
Total, other adverse events
71 / 71
serious
Total, serious adverse events
31 / 71

Outcome results

Primary

Number of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0

Time frame: Prior to each cycle and 30 days after the last cycle (average of 5 months)

Population: Eligible and treated patients

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
Docetaxel Plus TrabectedinNumber of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0Thrombocytopenia7 Participants
Docetaxel Plus TrabectedinNumber of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0Neutropenia21 Participants
Docetaxel Plus TrabectedinNumber of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0Leukopenia21 Participants
Docetaxel Plus TrabectedinNumber of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0Anemia5 Participants
Docetaxel Plus TrabectedinNumber of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0Other hematologic2 Participants
Docetaxel Plus TrabectedinNumber of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0Constitutional8 Participants
Docetaxel Plus TrabectedinNumber of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0Nausea6 Participants
Docetaxel Plus TrabectedinNumber of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0Vomiting7 Participants
Docetaxel Plus TrabectedinNumber of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0Gastrointestinal11 Participants
Docetaxel Plus TrabectedinNumber of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0Hemorrhage1 Participants
Docetaxel Plus TrabectedinNumber of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0Infection10 Participants
Docetaxel Plus TrabectedinNumber of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0Metabolic10 Participants
Docetaxel Plus TrabectedinNumber of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0Musculoskeletal3 Participants
Docetaxel Plus TrabectedinNumber of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0Other neurological2 Participants
Docetaxel Plus TrabectedinNumber of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0Pain6 Participants
Docetaxel Plus TrabectedinNumber of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0Pulmonary2 Participants
Primary

Objective Tumor Response

Response is measured according to Response Evaluation Criteria in Solid Tumors Criteria (RECIST v 1.0): Complete Response (CR) is disappearance of all target and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Partial Response (PR) is at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD. Disease Progression is at least a 20% increase in the sum of LD of target lesions taking as references the smallest sum LD or the appearance of new lesions within 8 weeks of study entry. Stable Disease is any condition not meeting the above criteria. Indeterminate is defined as having no repeat tumor assessments following initiation of study therapy6

Time frame: every other cycle for the first 6 months; then every 3 months thereafter (up to 5 years)

Population: Total number eligible and evaluable

ArmMeasureGroupValue (NUMBER)
Docetaxel Plus TrabectedinObjective Tumor ResponsePartial response21 participants
Docetaxel Plus TrabectedinObjective Tumor ResponseStable disease32 participants
Docetaxel Plus TrabectedinObjective Tumor ResponseDisease progression17 participants
Docetaxel Plus TrabectedinObjective Tumor ResponseIndeterminate1 participants
Secondary

Duration of Progression-free Survival and Overall Survival

Time frame: up to 5 years

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026