A Phase 1b Study of Paclitaxel And Ricolinostat For The Treatment Of Gynecological Cancer

NCT02661815 | Terminated Phase 1 Results DMC

• 1 other identifier: 15-483
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 2

Brief Summary

Participants with Ovarian, Fallopian Tube, or Peritoneal Cancer that has recurred within 12 months of prior treatment that includes Platinum Chemotherapy are invited to take part in this study. This research study is studying a combination of a new chemotherapy drug called Ricolinostat together with the chemotherapy Paclitaxel and a drug called Bevacizumab as a possible treatment for this diagnosis.

Conditions

Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Carcinoma

Outcome Measures

Primary Outcomes (2)

• Analysis Report on the MTD In The Dose Escalation Portion Of The Study

  Not assessed, the MTD was not reached as the study was terminated.

  2 years

• Best Overall Response Measured From, Start Of Treatment To The End

  This is now the primary outcome measure as the study was terminated prematurely.

  13 months

Secondary Outcomes (3)

• Peripheral Neurotoxicity Assessed Using TNS by Measuring 5 Categories

  0 years

• Duration Of Overall Response, Measured From The Time Measurement Criteria Are Met For PR or CR Until The First Date Recurrent Or Progressive Disease Is Objectively Documented.

  2 years

• Progression-free Survival (PFS)

  2 years

Study Arms (4)

Phase 1 Expansion Cohort A

EXPERIMENTAL

Paclitaxel 80mg/m2 weekly days 1, 8, and 15 of a 28-day cycle Ricolinostat dosing as identified as the RP2D combination dose

Drug: Paclitaxel; Drug: Ricolinostat

Phase 1 Expansion Cohort B

EXPERIMENTAL

Paclitaxel 70mg/m2 weekly days 1, 8, and 15 of a 28-day cycle Ricolinostat dosing as identified as the RP2D combination dose

Drug: Paclitaxel; Drug: Ricolinostat

Phase 1 Expansion Cohort C

EXPERIMENTAL

Paclitaxel 80mg/m2 weekly days 1, 8, and 15 of a 28-day cycle Bevacizumab 10mg/kg days 1 and 15 of a 28-day cycle Ricolinostat dosing as identified as the RP2D combination dose

Drug: Paclitaxel; Drug: Ricolinostat; Drug: Bevacizumab

Phase 1 Escalation Cohort

EXPERIMENTAL

Ricolinostat with weekly paclitaxel dosed at 80 mg/m2 per week (3 out of 4 weeks).

Drug: Paclitaxel; Drug: Ricolinostat

Interventions

Paclitaxel DRUG

Please see arm/group description.

Also known as: Taxol

Phase 1 Escalation Cohort; Phase 1 Expansion Cohort A; Phase 1 Expansion Cohort B; Phase 1 Expansion Cohort C

Ricolinostat DRUG

Please see arm/group description.

Also known as: ACY-1215

Phase 1 Escalation Cohort; Phase 1 Expansion Cohort A; Phase 1 Expansion Cohort B; Phase 1 Expansion Cohort C

Bevacizumab DRUG

Please see arm/group description.

Also known as: Avastin

Phase 1 Expansion Cohort C

Eligibility Criteria

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

You may qualify if:

• Participants must have recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal carcinoma, recurrent endometrial cancer, or recurrent cervical cancer. Histologic documentation of the original primary tumor is required via the pathology report.
• Participants must have measurable disease by RECIST 1.1 criteria. See Section 11 for the evaluation of measurable disease.
• Participants must have had at least one prior platinum-based chemotherapeutic regimen for management of primary disease (e.g., a regimen containing carboplatin, cisplatin, or another organoplatinum compound). This initial treatment may have included intraperitoneal therapy, consolidation, biologic/targeted (non-cytotoxic) agents (e.g., bevacizumab) or extended therapy administered after surgical or non-surgical assessment.
• Participants are allowed to receive, but are not required to receive, biologic/targeted (non-cytotoxic) therapy as part of their primary treatment regimen.
• Participants must have recurrence within 12 months of their last platinum-containing regimen.
• Age 18 years or older
• ECOG performance status 0 or 1
• Life expectancy of greater than 16 weeks
• Participants must have normal organ and marrow function as defined below:
• Leukocytes ≥3,000/mcL
• Absolute neutrophil count ≥1,500/mcL
• Platelets ≥100,000/mcL
• Total bilirubin within normal institutional limits
• AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal
• Creatinine within normal institutional limits OR

You may not qualify if:

• Participants who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. In addition, no small molecule kinase inhibitors or any other type of investigational agent may have been administered within 4 weeks before first dose of study treatment.
• Participants may not be receiving any other investigational agents for treatment of their cancer.
• No hormonal therapy is allowed within 1 week of initiating study treatment.
• Participants may not have had radiation to \>25% of the bone marrow.
• Prior treatment with a histone deacetylase inhibitor.
• Prior treatment with weekly paclitaxel for recurrent or persistent disease is not allowed. Participants may have received weekly paclitaxel as part of treatment for newly diagnosed cancer, but may not have received it as maintenance therapy following their initial therapy with platinum and taxane therapy.
• Participants with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• History of severe allergic reactions attributed to compounds of similar chemical or biologic composition to either paclitaxel or Ricolinostat. Patients who require administration of paclitaxel through a desensitization procedure are not eligible for this study.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patients with chronic viral illnesses such as HIV-positivity and active hepatitis B or C are ineligible because they are at increased risk of lethal infections when treated with marrow-suppressive therapy.
• Any signs, symptoms, and/or radiographic evidence of a complete or partial bowel obstruction
• Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer and other specific malignancies as noted below, are excluded if there is any evidence of other malignancy being present within the last three years. Patients are also excluded if their previous cancer treatment contraindicates this protocol therapy.
• Carcinoma in situ of the breast or cervix
• Primary endometrial cancer meeting the following conditions: Stage not greater than IA, grade 1 or 2, no more than superficial myometrial invasion, without vascular or lymphatic invasion; no poorly differentiated subtypes, including papillary serous, clear cell, or other FIGO grade 3 lesions.
• Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment of ovarian, fallopian tube, or primary peritoneal cancer within the last three years are excluded. Patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Celgene Corporation: collaborator

Study Sites (2)

Massacusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Ovarian Neoplasms; Fallopian Tube Neoplasms

Interventions

Paclitaxel; ricolinostat; Bevacizumab

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

Results Point of Contact

• Title: Dr. Joyce Liu
• Organization: Dana-Farber Cancer Insitute

joyce_liu@dfci.harvard.edu

617-632-5269

Study Officials

• Joyce Liu, MD MPH

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Joyce Liu, MD, MPH

Study Record Dates

• First Submitted: January 20, 2016
• First Posted: January 25, 2016
• Study Start: June 15, 2016
• Primary Completion: June 28, 2017
• Study Completion: July 28, 2017
• Last Updated: November 8, 2019
• Results First Posted: November 8, 2019

Record last verified: 2019-11

Locations

US (2)