Safety Study of PLX3397 and Paclitaxel in Patients With Advanced Solid Tumors

NCT01525602 | Completed Phase 1 Results

• 1 other identifier: PLX108-07
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 8

Brief Summary

This was a 3-part study designed to explore the safety and tolerability of escalating doses of PLX3397 with weekly paclitaxel to establish a recommended Phase 2 dose (RP2D), to confirm RP2D in participants with advanced non-resectable solid tumors, and to determine the efficacy of PLX3397 600 mg twice daily (BID) administered in combination with weekly paclitaxel in participants with advanced, metastatic or non-resectable, platinum-resistant or -refractory epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.

Conditions

Solid Tumors

Keywords

advanced, incurable solid tumors

Outcome Measures

Primary Outcomes (4)

• Percentage of Participants With Treatment-emergent Adverse Events (>10%) Classified by Preferred Term Following PLX3397 Administered in Combination With Paclitaxel (Parts 1 and 2) (Safety Population)

  Treatment-emergent adverse events (TEAEs) reported by \>10% of all participants in Parts 1 and 2 are reported.

  From post first dose up to 28 days after the last dose, up to 5 years 9 months

• Percentage of Participants With TEAEs (>10%) Classified by Preferred Term Following PLX3397 Administered in Combination With Paclitaxel (Part 3) (Safety Population)

  Treatment-emergent adverse events (TEAEs) reported by \>10% of all participants in Part 3 are reported.

  From post first dose up to 28 days after the last dose, up to 5 years 9 months

• Best Overall Tumor Response Based on RECIST V1.1 Following PLX3397 Administered in Combination With Paclitaxel (Parts 1 and 2) (Efficacy Evaluable Population)

  Best overall tumor response (complete response \[CR\], partial response \[PR\], stable disease \[SD\], progressive disease \[PD\]) is reported, including participants who were not evaluable (NE). RECIST v1.1 for target lesions are assessed by magnetic resonance imaging, computed tomography, or positron emission tomography-computed tomography and are summarized as: CR, Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm; PR, At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; PD, at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (includes the baseline sum). In addition, the sum must also demonstrate an absolute increase of at least 5 mm; SD, Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

  From post first dose up to 5 years 9 months post dose

• Best Overall Tumor Response Based on RECIST V1.1 Following PLX3397 Administered in Combination With Paclitaxel (Part 3) (Efficacy Evaluable Population)

  Best overall tumor response (complete response \[CR\], partial response \[PR\], stable disease \[SD\], progressive disease \[PD\]) is reported, including participants who were not evaluable (NE). RECIST v1.1 for target lesions are assessed by magnetic resonance imaging, computed tomography, or positron emission tomography-computed tomography and are summarized as: CR, Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm; PR, At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; PD, at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (includes the baseline sum). In addition, the sum must also demonstrate an absolute increase of at least 5 mm; SD, Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

  From 26 days (CR and PR) and 54 days (SD) up to 5 years 9 months post dose

Secondary Outcomes (9)

• Duration of Response Following PLX3397 Administered in Combination With Paclitaxel (Parts 1 and 2) (Efficacy Evaluable Population)

  From the date of initial response until disease progression or death, whichever occurs first, up to 5 years 9 months post dose

• Duration of Response Following PLX3397 Administered in Combination With Paclitaxel (Part 3) (Efficacy Evaluable Population)

  From the date of initial response until disease progression or death, whichever occurs first, up to 5 years 9 months post dose

• Progression-free Survival Following PLX3397 Administered in Combination With Paclitaxel (Part 3) (Efficacy Evaluable Population)

  From the first day of treatment to the first documented disease progression or date of death, whichever occurred first, up to 5 years 9 months post dose

• A Summary of Pharmacokinetic Parameter (Tmax) Following Exposure to PLX3397 (Parts 1 and 3)

  Cycle 1, Day 15

• A Summary of Pharmacokinetic Parameter (Cmax) Following Exposure to PLX3397 (Parts 1 and 3)

  Cycle 1, Day 15

Study Arms (3)

Part 1

EXPERIMENTAL

Open-label, sequential PLX3397 single-agent dose escalation in combination with paclitaxel in approximately 30 patients with advanced solid tumors. Enrollment completed. (Closed to recruitment)

Drug: PLX3397; Drug: Paclitaxel

Part 2

EXPERIMENTAL

Extension cohort at the RP2D of single-agent PLX3397 in combination with paclitaxel in approximately 30 patients in advanced solid tumors. Enrollment completed. (Closed to recruitment)

Drug: PLX3397; Drug: Paclitaxel

Part 3

EXPERIMENTAL

Extension cohort at the RP2D of single-agent PLX3397 in combination with paclitaxel in approximately 30 patients with advanced, metastatic, or non-resectable, platinum-resistant or -refractory epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer. (Closed to recruitment)

Drug: PLX3397; Drug: Paclitaxel

Interventions

PLX3397 DRUG

PLX3397 tablets, 200mg

Also known as: Pexidartinib

Part 1; Part 2; Part 3

Paclitaxel DRUG

Paclitaxel IV

Also known as: Onxol

Part 1; Part 2; Part 3

Eligibility Criteria

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

You may qualify if:

• Patients with:
• Part 1 (enrollment closed): an advanced, incurable solid tumor
• Part 2 (enrollment closed): an advanced, incurable solid tumor for whom a taxane would be considered a reasonable chemotherapy option
• Part 3 (enrollment closed): advanced, metastatic or non-resectable epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer with
• platinum-resistant cancer, defined as disease that responded to a platinum-containing chemotherapy regimen, but demonstrated recurrence within six months following the completion of that platinum-containing regimen, OR
• platinum-refractory cancer, defined as disease failed to achieve at least a partial response to a platinum-containing regimen (i.e., stable disease or actual disease progression), AND
• have not been treated with a taxane within six months of Cycle 1 Day 1 (C1D1), AND
• have not been treated with weekly paclitaxel after first-line treatment in which weekly paclitaxel plus a platinum is permitted
• Part 3: Patients must have target (≥2 cm diameter) or non-target lesion cancer that is accessible for core biopsies before starting on study and after one cycle of treatment.
• Patients with stable brain metastases are eligible for this trial. However, patients must not have required steroid treatment for their brain metastases within 30 days of Screening.
• Bone-directed therapy (e.g., bisphosphonates or denosumab) is permitted.
• Washout from any prior investigational therapy of at least five times the T1/2 prior to C1D1
• Washout from any prior biologic or targeted therapy at least 4 weeks or five times the plasma half-life (T1/2) (whichever is shorter) prior to C1D1
• Washout from prior chemotherapy of at least 2 weeks or 1 elimination half-life, whichever is longer, prior to C1D1
• Washout from prior hormonal therapy of at least 2 weeks prior to C1D1

You may not qualify if:

• Presence of an active secondary malignancy.
• Patients with a non-melanomatous, in situ malignancy or disease that is completely resectable with surgery may be considered after discussion with the Medical Monitor
• Patients with a completely treated prior malignancy with no evidence of disease for ≥3 years are eligible
• Refractory nausea and vomiting, malabsorption, external biliary shunt or significant small bowel resection that would preclude adequate absorption of PLX3397
• Ongoing treatment with any other investigational therapy
• Prior anaphylactic or severe hypersensitivity reaction to paclitaxel or Cremophor-containing agent.
• Persistent grade 2 fatigue at Baseline.
• Severe, concurrent illness including congestive heart failure, significant cardiac disease and uncontrolled hypertension, that would likely prevent the patient from being able to comply with the study protocol
• Active untreated infection
• Known chronic active Hepatitis B or C, or HIV infection

Sponsors & Collaborators

• Daiichi Sankyo: lead
• Plexxikon: collaborator

Study Sites (8)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Univeristy of California, San Francisco

San Francisco, California, 94143, United States

Location

University of Colorado, Anschutz Cancer Pavilion

Aurora, Colorado, 80045, United States

Location

Sylvester Comprehensive Cancer Center/UMHC

Miami, Florida, 33136, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

University Hospitals of Cleveland

Cleveland, Ohio, 44106, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

University of Utah, Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Interventions

pexidartinib; Paclitaxel

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: Medical Director
• Organization: Daiichi Sankyo Inc.

CTRinfo@dsi.com

908-992-6400

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: January 31, 2012
• First Posted: February 3, 2012
• Study Start: May 1, 2012
• Primary Completion: December 1, 2017
• Study Completion: February 1, 2018
• Last Updated: July 16, 2020
• Results First Posted: July 16, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.

Locations

US (8)