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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Plexxikon
ClinicalTrials.gov Identifier:
NCT01525602
First received: January 31, 2012
Last updated: December 9, 2014
Last verified: December 2014
  Purpose

This is an open-label, two-part, phase 1b study:

PART 1 is to determine the Recommended Phase 2 Dose (RP2D) of PLX3397 when given in combination with weekly standard dose paclitaxel in patients with advanced solid tumors.

PART 2 is to determine efficacy and safety of PLX3397 administered at RP2D in combination with paclitaxel.


Condition Intervention Phase
Solid Tumors
Drug: PLX3397 + Paclitaxel
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1b Study to Assess the Safety of PLX3397 and Paclitaxel in Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by Plexxikon:

Primary Outcome Measures:
  • Safety--Subject incidence of adverse events [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Subjects will take oral doses of PLX3397 twice a day using a continuous dosing regimen. Paclitaxel IV will be administered weekly in each 28-day treatment cycle. Physical examinations, vital signs, 12-lead electrocardiograms (ECG), adverse events, hematology, and serum chemistry will be used to assess safety throughout the study. Adverse events will be monitored and reviewed for safety issues/abnormal changes in the above mentioned tests.


Secondary Outcome Measures:
  • Response to treatment according to RECIST criteria [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 36
Study Start Date: May 2012
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 600 mg/day PLX3397 + Paclitaxel weekly
Starting Level (Level 0)
Drug: PLX3397 + Paclitaxel
oral dose 600 mg/day PLX3397 (Days 1-28); 80 mg/m2 Paclitaxel IV, ~60 minutes weekly ±48 hours (Days 1, 8, 15, and 22)
Other Names:
  • PLX3397
  • Paclitaxel
Experimental: 800 mg/day PLX3397 + Paclitaxel weekly
Level 1
Drug: PLX3397 + Paclitaxel
oral dose 800 mg/day PLX3397 (Days 1-28); 80 mg/m2 Paclitaxel IV, ~60 minutes weekly ±48 hours (Days 1, 8, 15, 22)
Other Names:
  • PLX3397
  • Paclitaxel
Experimental: 1000 mg/day PLX3397 + Paclitaxel weekly
Level 2
Drug: PLX3397 + Paclitaxel
oral dose 1000 mg/day PLX3397 (Days 1-28); 80 mg/m2 Paclitaxel IV, ~60 minutes weekly ±48 hours (Days 1, 8, 15, and 22)
Other Names:
  • PLX3397
  • Paclitaxel
Experimental: 1200 mg/day PLX3397 + Paclitaxel
Level 3
Drug: PLX3397 + Paclitaxel
oral dose 1200 mg/day PLX3397 (Days 1-28); 80 mg/m2 Paclitaxel IV, ~60 minutes weekly ±48 hours (Days 1, 8, 15, and 22)
Other Names:
  • PLX3397
  • Paclitaxel
Experimental: 1600 mg/day PLX3397 + Paclitaxel
Level 4
Drug: PLX3397 + Paclitaxel
oral dose 1600 mg/day PLX3397 (Days 1-28); 80 mg/m2 Paclitaxel IV, ~60 minutes weekly ±48 hours (Days 1, 8, 15, and 22)
Other Names:
  • PLX3397
  • Paclitaxel
Experimental: 400 mg/day PLX3397 + Paclitaxel weekly
Level -1
Drug: PLX3397 + Paclitaxel
oral dose 400 mg/day PLX3397 (Days 1-28); 80 mg/m2 Paclitaxel IV, ~60 minutes weekly ±48 hours (Days 1, 8, 15, and 22)
Other Names:
  • PLX3397
  • Paclitaxel

Detailed Description:

This is a non-randomized, open label, two-part, phase 1b study.

PART 1 is employing a standard 3+3 sequential dose escalation design to determine the Recommended Phase 2 Dose (RP2D) of PLX3397, a novel inhibitor of the CSF-1 receptor (Fms), when administered in combination with paclitaxel in patients with advanced, incurable solid tumors. Treatment with PLX3397 will consist of oral administration with the starting dose of 600 mg/day for 28 days. Paclitaxel will be administered once weekly over approximately 60 minutes in each 28-day treatment cycle. The planned cohorts are Cohort 1: 600 mg/day; Cohort 2: 800 mg/day; Cohort 3: 1000 mg/day and 1600 mg/day.

Each dose level cohort will enroll 3-6 patients. Enrollment into the next higher dose level will begin only if the first 3 patients enrolled into the cohort complete the 28-day observation period without the occurrence of a Dose-Limiting Toxicity (DLT). If one of the 3 initial patients at a given dose level experiences a DLT, the cohort at this dose level will be expanded to include an additional 3 patients (6 patients total).

If ≥ 2/6 patients experience a DLT, then dose escalation will be stopped.

Enrollment is planned to include approximately 30 patients recruited from approximately 3-4 sites. The total number of patients to be enrolled will depend on the number of cohorts and whether a cohort requires 3 or 6 patients. During the first cycle, a patient that does not receive at least 21 days of PLX3397 or does not receive at least 3 of 4 doses of paclitaxel for reasons other than a DLT, the patient may be replaced.

PART 2 is a non-randomized, open-label study of PLX3397 administered at RP2D in combination with paclitaxel in approximated 15 patients (including all RP2D-treated patients in Part 1 and Part 2) with advanced solid tumors in which treatment with taxane is considered appropriate.

Study treatment will be provided until disease progression, unacceptable or dose-limiting toxicity, death, withdrawal of consent, study termination by Sponsor, or if the Investigator and patient agree that it is in the patient's best interests to discontinue.

The primary objective of this phase 1b study is to establish the DLTs and RP2D of PLX3397 when given in combination with weekly standard dose Paclitaxel.

The secondary objectives include (1) evaluation of overall safety and tolerability of PLX3397 in combination with paclitaxel, (2) explore the efficacy of PLX3397 in combination with paclitaxel in patients with advance solid tumors, and (3) determine the PK of PLX3307 when administered in combination with paclitaxel.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

PART 1

  • Advanced, incurable solid tumor. PART 2
  • Advanced, incurable solid tumor, received ≤2 prior chemo regimeds for primary malignancy, and a taxane considered reasonable treatment option.

OTHER

  • Patients with stable brain metastases are eligible. 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. However, patients should not have started bone-directed therapy within 2 weeks of C1D1, and new bone-directed therapy should not be initiated during the first 4 weeks of study (i.e., cycle 1).
  • Washout from any prior investigational therapy of at least 28 days prior to Cycle 1, Day 1 (i.e.,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.
  • Washout of at least 2 weeks from the most recent radiation treatment prior to C1D1.
  • Resolution of all prior treatment-related toxicities to Grade 1 or less, except for Grade 2 fatigue or alopecia prior to C1D1.
  • Age 18 years or older.
  • ECOG performance status 0-2, inclusive.
  • Anticipated life expectancy of at least 12 weeks.
  • Adequate bone marrow reserve: ANC ≥ 1000/mm3, platelets ≥ 100,000/mm3.
  • Adequate renal function: serum creatinine < 1.5X ULN or calculated CrCl > 60 mL/min using Cockcroft-Gault formula. GFR = [(140-age)*(weight in kg)*(0.85 if female)]/(72*Cr)
  • Adequate hepatic function: AST and ALT < 2.5X ULN, Total and Direct Bilirubin < 1.5X ULN. However, in the presence of liver metastases, AST and ALT must be < 5X ULN
  • Cardiac ejection fraction ≥ 50%, and QTcF < 450 ms (male) or <470 ms (female) on ECG at Baseline.

Fridericia's Formula: QTcF = (QT)/RR0.33

  • Able to swallow capsules and maintain adequate hydration.
  • Ability to give written informed consent and willing to comply with the requirements of the protocol.
  • Women of child-bearing potential must agree to use an effective method of birth control during treatment and for three months after receiving their last dose of study drug. Fertile men must also agree to use an acceptable method of birth control while on study drug and for at least 3 months after last dose.

Exclusion Criteria:

  • 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.
  • The presence of a medical or psychiatric condition that, in the opinion of the Principal Investigator, makes the patient inappropriate for inclusion in this study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01525602

Locations
United States, California
UCSF
San Francisco, California, United States, 94143-1710
United States, Ohio
University Hospitals of Cleveland
Cleveland, Ohio, United States, 44106
Ohio State University
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Plexxikon
Investigators
Principal Investigator: Neelesh Sharma, MD, PhD University Hospitals of Cleveland - Cleveland, OH
Principal Investigator: Hope Rugo, MD UCSF - San Francisco, CA
Principal Investigator: Robert Wesolowski, MD Ohio State University
  More Information

No publications provided

Responsible Party: Plexxikon
ClinicalTrials.gov Identifier: NCT01525602     History of Changes
Other Study ID Numbers: PLX108-07
Study First Received: January 31, 2012
Last Updated: December 9, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Plexxikon:
advanced, incurable solid tumors

Additional relevant MeSH terms:
Paclitaxel
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on March 03, 2015