Postoperative Adjuvant Chemotherapy With Bevacizumab and Maintenance Bevacizumab After Neoadjuvant Chemotherapy for Ovarian Cancer

NCT02022917 | Completed Phase 2 DMC

• 2 other identifiers: AGOG11-003TGOG3008
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 5

Brief Summary

This study is to determine the feasibility of postoperative platinum-based chemotherapy plus adjuvant and maintenance bevacizumab after neoadjuvant chemotherapy followed by interval surgery in patients with extensive stage IIIC or IV ovarian, tubal, and peritoneal cancer.

Conditions

Epithelial Ovarian Cancer

Keywords

ovarian cancer.; tubal cancer; peritoneal cancer

Outcome Measures

Primary Outcomes (1)

• Significant event rate of the regimen (neoadjuvant carboplatin, paclitaxel, and bevacizumab)

  Significant AEs include: 1. Hypertension ≥ grade 3 2. Proteinuria ≥ grade 3 3. GI perforation, abscesses and fistulae (any grade) 4. Wound healing complications ≥ grade 3 5. Haemorrhage ≥ grade 3 (any grade CNS bleeding; ≥ grade 2 haemoptysis) 6. Arterial thromboembolic events (any grade) 7. Venous thromboembolic events ≥ grade 3 8. PRES (any grade) 9. CHF ≥ grade 3 10. Non-GI fistula or abscess ≥ grade 2

  Up to 30 days after the last treatment

Secondary Outcomes (1)

• Progression free survival (PFS)

  Every 3 months during treatment and every 6 months for three years post-treatment

Study Arms (1)

Epithelial Ovarian Cancer

EXPERIMENTAL

Neoadjuvant Carboplatin, Paclitaxel, and Bevacizumab 21 day cycles of carboplatin, paclitaxel, and bevacizumab

Drug: Bevacizumab

Interventions

Bevacizumab DRUG

Bevacizumab 15 mg/ Kg (from post-op cycle 2) intravenous infusion for 30 minutes in a 21 days' cycle for at least three cycles (best to 6 cycles) followed by 3-weekly maintenance bevacizumab 15 mg/ Kg intravenous infusion for 17 cycles.

Also known as: Avastin

Epithelial Ovarian Cancer

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• previously untreated histologically proven epithelial ovarian cancer, tubal or peritoneal primary carcinoma, of FIGO stage IV or extensive stage III deem not feasible for primary cytoreductive surgery
• histologic epithelial cell types as follows: Serous adenocarcinoma, endometrioid adenocarcinoma, mucinous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, transitional cell carcinoma, malignant Brenner's Tumor, or adenocarcinoma not otherwise specified (N.O.S.).
• well informed about the rationale of neoadjuvant chemotherapy as an alternative to upfront surgery followed by adjuvant chemotherapy and accepted treatment with three to four cycles of neoadjuvant treatment with three to four cycles of platinum-based regimen without progression followed by interval cytoreductive surgery
• performance status of ECOG 0-2
• adequate hematopoietic function is defined as below:
• ANC ≥ 1,500/uL, equivalent to Common Toxicity Criteria for Adverse Events v4.03 (CTCAE) Grade1.
• Platelets ≥ 100,000/uL (CTCAE Grade 0-1).
• INR is ≦ 1.5 (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin) and aPTT \< 1.2 x ULN
• adequate organ function is defined as below:
• total bilirubin ≦ 1.5 × ULN (CTCAE Grade 1).
• ALT/AST≦2.5 x ULN and alkaline phosphatase≦2.5 x ULN (CTCAE Grade 1)
• serum creatinine ≦ 1.5 × ULN (CTCAE Grade 1).
• adequate neurologic function, neuropathy (sensory and motor) ≦ CTCAE Grade 1
• age 20-75 years old
• Patients must have measurable and non-measurable disease. Patients may or may not have cancer-related symptoms.

You may not qualify if:

• borderline ovarian tumors, recurrent epithelial ovarian, tubal or peritoneal or non-epithelial cancers
• history or evidence upon physical examination of CNS disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarrachnoid hemorrhage within six months of the first date of treatment on this study.
• Patients with synchronous primary endometrial cancer, or a past history of primary endometrial cancer, are excluded.
• other malignancy with exception of curative treated non-melanoma skin cancer or cervical carcinoma in situ within 5 years prior to entering the study
• patients who have received any targeted therapy (including but not limited to vaccines, antibodies, tyrosine kinase inhibitors) or hormonal therapy for management of their ovarian, peritoneal primary or fallopian tube carcinoma
• patients with serious, non-healing wound, ulcer, or bone fracture.
• patients with granulating incisions healing by secondary intention with no evidence of fascial dehiscence or infection are eligible but require weekly wound examinations.
• history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess or active gastrointestinal bleeding within 6 months.
• patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels
• clinically significant proteinuria. Urine protein should be screened by urine protein-creatinine ratio (UPCR). The UPCR has been found to correlate directly with the amount of protein excreted in a 24 hour urine collection. Specifically, a UPCR of 1.0 is equivalent to 1.0 gram of protein in a 24 hour urine collection. Obtain at least 4 ml of a random urine sample in a sterile container (does not have to be a 24 hour urine). Send sample to lab with request for urine protein and creatinine levels \[separate requests\]. The lab will measure protein concentration (mg/dL) and creatinine concentration (mg/dL) The UPCR is derived as follows: protein concentration (mg/dL)/creatinine (mg/dL). Patients must have a UPCR \< 1.0 to allow participation in the study.
• clinical significant cardiovascular disease
• Uncontrolled hypertension, defined as systolic \>150 mm Hg or diastolic\> 90 mm Hg.
• Prior history of hypertensive crisis or hypertensive encephalopathy
• active cardiac disease e.g. decompensated myocardial infarction within the 6-month period preceding entry into the study.
• New York Heart Association (NYHA) Grade II or greater congestive heart failure

Sponsors & Collaborators

• Chang Gung Memorial Hospital: lead
• Hoffmann-La Roche: collaborator
• Asian Gynecologic Oncology Group: collaborator
• Taiwanese Gynecolgic Oncology Group: collaborator

Study Sites (5)

Department of Obstetrics & Gynecology, Chang Gung Memorial Hospital

Chiayi City, Taiwan

Location

Department of Obstetrics & Gynecology Chang Gung Memorial Hospital

Kaohsiung City, Taiwan

Location

China Medical University Hospital

Taichung, Taiwan

Location

Wan Fang Hospital, Taipei Medical University,

Taipei, Taiwan

Location

Division of Gynecologic Oncology, Department of Obstetrics & Gynecology Chang Gung Memorial Hospital, Linkou Medical Center

Taoyuan District, Taiwan

Location

MeSH Terms

Conditions

Carcinoma, Ovarian Epithelial; Ovarian Neoplasms

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Chyong-Huey Lai, MD

  Chang Gung Memorial Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D.

Study Record Dates

• First Submitted: December 11, 2013
• First Posted: December 30, 2013
• Study Start: March 1, 2014
• Primary Completion: January 1, 2021
• Study Completion: January 1, 2021
• Last Updated: January 27, 2021

Record last verified: 2021-01

Locations

TW (5)