Dose-Escalation Study of Intraperitoneal (IP) Cisplatin, IV/IP Paclitaxel, IV Bevacizumab, and Oral Olaparib for Newly Diagnosed Ovarian, Primary Peritoneal, and Fallopian Tube Cancer

NCT02121990 | Completed Phase 1

• 1 other identifier: 10-220
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to test the safety of the drug olaparib at different dose levels. It will be given with the standard initial chemotherapy for cancer as well as a drug called bevacizumab.

Conditions

Ovarian Cancer; Primary Peritoneal Cancer; Fallopian Tube Cancer

Keywords

(IP) Cisplatin; IV/IP Paclitaxel; IV Bevacizumab; Oral Olaparib (AZD2281); Optimally Debulked; Stage II/III; Ovary; Pertoneum; 10-220

Outcome Measures

Primary Outcomes (1)

• maximum tolerated dose (MTD)

  This is a dose-finding Phase 1 study, which employs a 3+3 design, and aims to identify the MTD of a combination of traditional and novel agents for front-line therapy of optimally debulked ovarian cancer.

  1 year

Secondary Outcomes (1)

• Toxicity

  1 year

Study Arms (1)

Cisplatin, Paclitaxel, bevacizumab & olaparib

EXPERIMENTAL

All treatments will be given in the outpatient setting. A cycle is 21 days. The sequence of infusions on Day 1 will be IV paclitaxel (135 mg/m2), then IV bevacizumab (15 mg/kg, beginning Cycle 2). On Day 2 patients will receive IP cisplatin (75 mg/m2). Patients will be given twice-daily treatment with oral olaparib in cycles 1-6 for 7 consecutive days, starting on Day 2 (Days 2-8). IP paclitaxel (60 mg/m2) will be given on Day 8. Sequential cohorts of 3 patients will receive escalating doses of olaparib (50mg BID, 100mg BID, 200mg BID).

Drug: Paclitaxel,; Drug: Bevacizumab; Drug: Cisplatin; Drug: Olaparib

Interventions

Paclitaxel, DRUG

Cisplatin, Paclitaxel, bevacizumab & olaparib

Bevacizumab DRUG

Cisplatin, Paclitaxel, bevacizumab & olaparib

Cisplatin DRUG

Cisplatin, Paclitaxel, bevacizumab & olaparib

Olaparib DRUG

Cisplatin, Paclitaxel, bevacizumab & olaparib

Eligibility Criteria

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

You may qualify if:

• Subjects with histologic diagnosis of epithelial ovarian carcinoma, primary peritoneal carcinoma, or fallopian tube carcinoma, following initial surgery. All subjects must have had appropriate surgery for ovarian, primary peritoneal, or fallopian tube carcinoma with appropriate tissue available for histologic evaluation to confirm diagnosis and stage. Pathology must be verified at Memorial Sloan-Kettering Cancer Center. Patients with initial cytoreduction surgery performed at outside hospitals will be eligible for this protocol.
• Patients with the following histologic cell types are eligible:
• High grade serous adenocarcinoma
• Endometrioid adenocarcinoma
• Undifferentiated carcinoma
• Clear cell adenocarcinoma
• Mixed epithelial adenocarcinoma
• Adenocarcinoma not otherwise specified (N.O.S.)
• Carcinosarcoma
• Subjects must have a Karnofsky Performance Status (KPS) of ≥ 70%.
• Subjects must be entered no more than 12 weeks postoperatively.
• Subjects must agree to undergo genetic counseling and BRCA testing. Patients in the expansion cohort must have a germline BRCA 1 or 2 mutation.
• Physical and Laboratory Test Findings
• PT such that international normalized ratio (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 a PTT ≤ 1.5 times the upper limit of normal.
• Bone marrow function:

You may not qualify if:

• Subjects with a current diagnosis of epithelial ovarian tumor of low malignant potential (borderline carcinomas) are not eligible.
• Patients with synchronous primary endometrial cancer or a past history of endometrial cancer, unless all of the following conditions are met:
• Stage not greater than IB
• No more than superficial myometrial invasion
• No vascular or lymphatic invasion
• No poorly differentiated subtypes, including papillary serous, clear cell, or other FIGO Grade 3 lesions.
• Subjects who have received prior radiotherapy to any portion of the abdominal cavity or pelvis are excluded. Prior intravaginal brachytherapy is permitted. Prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than 3 years prior to enrollment, and the subject remains free of recurrent or metastatic disease.
• Patients who have received prior chemotherapy for any abdominal or pelvic tumor are excluded. Patients who have received neoadjuvant chemotherapy prior to their initial debulking are excluded. Patients may have received prior adjuvant chemotherapy for localized breast cancer.
• With the exception of non-melanoma skin cancer and other specific malignancies as noted above, subjects with other invasive malignancies who had (or have) any evidence of the other cancer present within the last 3 years or whose previous cancer treatment contraindicates this protocol therapy are excluded.
• Patients who have received prior bevacizumab (or any other VEGF targeted agent) or prior PARP inhibitor.
• Subjects with acute hepatitis.
• Subjects with active infection that requires parenteral antibiotics.
• \> Grade 1 hearing loss or tinnitus
• Patients who are pregnant or nursing.
• Patients under the age of 18.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• AstraZeneca: collaborator
• Genentech, Inc.: collaborator

Study Sites (5)

Memorial Sloan Kettering Cancer Center at Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Cancer Center @ Suffolk

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Cancer Center at Mercy Medical Center

Rockville Centre, New York, 11570, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Ovarian Neoplasms; Fallopian Tube Neoplasms

Interventions

Paclitaxel; Bevacizumab; Cisplatin; olaparib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; 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; Fallopian Tube Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Jason Konnor, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2014
• First Posted: April 24, 2014
• Study Start: April 21, 2014
• Primary Completion: August 19, 2020
• Study Completion: August 19, 2020
• Last Updated: August 21, 2020

Record last verified: 2020-08

Locations

US (5)