NCT02661815

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

Terminated Phase 1 Results posted Last updated 8 November 2019

What this trial tests

Phase 1 trial testing Paclitaxel in Ovarian Cancer in 6 participants. Terminated before completion.

Timeline

15 June 2016

Primary endpoint
28 June 2017

28 July 2017

Quick facts

Lead sponsor	Dana-Farber Cancer Institute
Phase	Phase 1
Status	Terminated
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	6
Start date	15 June 2016
Primary completion	28 June 2017
Estimated completion	28 July 2017
Sites	2 locations across United States

Drugs / interventions tested

• Paclitaxel — full drug profile →
• Ricolinostat
• Bevacizumab (Bevacizumab-Bvzr) — full drug profile →

Conditions studied

• Ovarian Cancer — all drugs for Ovarian Cancer →
• Fallopian Tube Cancer — all drugs for Fallopian Tube Cancer →
• Primary Peritoneal Carcinoma — all drugs for Primary Peritoneal Carcinoma →

Sponsor

Dana-Farber Cancer Institute

Who can join

18 and older, female only, with Ovarian Cancer or Fallopian Tube Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Analysis Report on the MTD In The Dose Escalation Portion Of The Study Primary · 2 years

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

Group	Value	95% CI
Phase 1 Escalation Cohort	NA

Best Overall Response Measured From, Start Of Treatment To The End Primary · 13 months

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

Partial Response

Group	Value	95% CI
Phase 1 Escalation Cohort	2

Stable Disease

Group	Value	95% CI
Phase 1 Escalation Cohort	2

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse event data was collected for 1 year, 1 month.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Phase 1 Expansion Cohort A

Serious: 0

Deaths: 0

Phase 1 Expansion Cohort B

Serious: 0

Deaths: 0

Phase 1 Expansion Cohort C

Serious: 0

Deaths: 0

Phase 1 Escalation Cohort

Serious: 1/6 (17%)

Deaths: 0/6

Serious adverse events (1 terms)

Reaction	System	Phase 1 Expansion Cohort A	Phase 1 Expansion Cohort B	Phase 1 Expansion Cohort C	Phase 1 Escalation Cohort
syncopal episode	Blood and lymphatic system disorders	—	—	—	—

Other adverse events (11 terms — click to expand)

Reaction	System	Phase 1 Expansion Cohort A	Phase 1 Expansion Cohort B	Phase 1 Expansion Cohort C	Phase 1 Escalation Cohort
nausea	Gastrointestinal disorders	—	—	—	—
vomiting	Gastrointestinal disorders	—	—	—	—
fatigue	General disorders	—	—	—	—
neutrophil count decreased	Investigations	—	—	—	—
alopecia	Skin and subcutaneous tissue disorders	—	—	—	—
localized edema	General disorders	—	—	—	—
anorexia	Metabolism and nutrition disorders	—	—	—	—
generalized muscle weakness	Musculoskeletal and connective tissue disorders	—	—	—	—
dysgeusia	Nervous system disorders	—	—	—	—
peripheral sensory neuropathy	Nervous system disorders	—	—	—	—
nail discoloration	Skin and subcutaneous tissue disorders	—	—	—	—

Most-reported serious reactions: syncopal episode.

Data from ClinicalTrials.gov NCT02661815 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials.
   Lin A, Giuliano CJ, Palladino A, John KM, et al · · 2019 · cited 549× · PMID 31511426 · DOI 10.1126/scitranslmed.aaw8412
2. Tumor Microenvironment in Ovarian Cancer: Function and Therapeutic Strategy.
   Yang Y, Yang Y, Yang J, Zhao X, et al · · 2020 · cited 168× · PMID 32850861 · DOI 10.3389/fcell.2020.00758
3. HDAC6 inhibition effectively reverses chemotherapy-induced peripheral neuropathy.
   Krukowski K, Ma J, Golonzhka O, Laumet GO, et al · · 2017 · cited 155× · PMID 28267067 · DOI 10.1097/j.pain.0000000000000893
4. Beyond symptomatic relief for chemotherapy-induced peripheral neuropathy: Targeting the source.
   Ma J, Kavelaars A, Dougherty PM, Heijnen CJ. · · 2018 · cited 133× · PMID 29461625 · DOI 10.1002/cncr.31248
5. Histone deacetylase 6 (HDAC6) deacetylates extracellular signal-regulated kinase 1 (ERK1) and thereby stimulates ERK1 activity.
   Wu JY, Xiang S, Zhang M, Fang B, et al · · 2018 · cited 37× · PMID 29259132 · DOI 10.1074/jbc.m117.795955
6. Epigenetics: A primer for clinicians.
   Paluch BE, Naqash AR, Brumberger Z, Nemeth MJ, et al · · 2016 · cited 37× · PMID 26969414 · DOI 10.1016/j.blre.2016.02.002
7. Pharmacological targeting of the cancer epigenome.
   Mabe NW, Perry JA, Malone CF, Stegmaier K. · · 2024 · cited 36× · PMID 38937652 · DOI 10.1038/s43018-024-00777-2
8. Bringing new medicines to women with epithelial ovarian cancer: what is the unmet medical need?
   Herzog TJ, Monk BJ. · · 2017 · cited 26× · PMID 28904804 · DOI 10.1186/s40661-017-0050-0