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Breast CancerPhase 1IOSI-NDU-001NCT02069158

Dose Finding Study Of PF-05212384 With Paclitaxel And Carboplatin In Patients With Advanced Solid Tumor

A Phase 1 study testing PF-05212384, Paclitaxel and Carboplatin in people with Breast Cancer and NSCLC, run by Cristiana Sessa at 1 site in Switzerland.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a phase Ib single arm, open-label, multiple dose, dose escalating, safety, pharmacokinetic and pharmacodynamic study of the combination of PF-05212384 with paclitaxel and carboplatin. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer, NSCLC, Ovary Cancer
What is being tested?
PF-05212384, Paclitaxel and Carboplatin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
1 siteSwitzerland
Study dates
Apr 2014to May 2019
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age >18 years.
  • Histological or cytological diagnosis of advanced/metastatic breast, NSCLC, ovarian and endometrial, small cell lung cancer (SCLC) and Head and Neck (HNSCC) cancer for which there is an indication to the use of paclitaxel and carboplatin.
  • For patients enrolled to Part 1, lesions may be measurable or non measurable; for patients enrolled to Part 2, at least one measurable lesion is requested.
  • All patients must provide an archived or fresh tumor sample; paired fresh tumor biopsies are mandatory for patients enrolled to Part 2 (at baseline and on Day 22 of Cycle 1).
  • ECOG Performance Status must be 0 or 1.
  • Adequate Bone Marrow Function, including:
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  • Absolute Neutrophil Count (ANC) ≥1,500/mm3 (or ≥1.5 x 109/L);
  • Platelets ≥100,000/mm3 (or ≥100 x 109/L);
  • Hemoglobin ≥9 g/dL.
  • Adequate renal function, including: serum creatinine ≤1.5 x upper limit of normal (ULN) or estimated creatinine clearance ≥ 60 ml/min as calculated using the method standard for the institution.
  • Adequate Liver Function, including:
  • Total serum bilirubin ≤1.0 mg/dL Aspartate and Alanine Aminotransferase AST \& ALT) ≤2.5 x ULN; ≤5.0 x ULN if there is liver involvement secondary to tumor.
  • Alkaline phosphatase ≤2.5 x ULN; (≤5 x ULN in case of bone metastasis).
  • Adequate glucose control, including no previous diagnosis of diabetes mellitus and HbA1c <7%.
  • Adequate cardiac function, including: 12 Lead ECG with normal tracing or non clinically significant changes that do not require medical intervention.
  • Resolved acute effects of any prior therapy to baseline severity or Grade
  • 1 CTCAE except for AEs not constituting a safety risk by Investigator judgment.
  • Serum/urine pregnancy test (for females of childbearing potential) negative at screening and at baseline.
  • Female patients must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of the trial and for at least 90 days after completion of treatment. Male patients must be surgically sterile or must agree to use effective contraception during the period of the trial and for at least 90 days after completion of treatment. The decision of effective contraception will be based on the judgment of the principal Investigator or a designated associate.
  • Willingness and ability to comply with the study scheduled visits, treatment plans, laboratory tests and other procedures.
  • Written informed consent.

Who cannot join

  • More than 2 prior lines of chemotherapy for advanced disease for Part 1, more than 1 prior line of chemotherapy for advanced disease for Part 2.
  • Resistance to platinum agents (progression during the treatment or within 3 month from the stop of the treatment).
  • Prior treatment with weekly paclitaxel with tumor progression.
  • Pre-existing neuropathy ≥ G2.
  • Patients with known active brain metastases. Patients with previously diagnosed brain metastases are eligible if they have completed their CNS treatment and have recovered from the acute effects of radiation therapy or surgery prior to the start of study medication, have discontinued corticosteroid treatment for these metastases for at least 4 weeks and are neurologically stable.
  • Chemotherapy, radiotherapy (other than palliative radiotherapy to lesions that will not be followed for tumor assessment on this study, ie, non target lesions), biological or investigational agents within 4 weeks of the start of the study treatment (6 weeks for mitomycin C or nitrosoureas).
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  • Any surgery (not including minor procedures such as lymph node biopsy, needle biopsy, and/or placement of port-a-cath) within 4 weeks of the start of the study treatment or not fully recovered from any side effects of previous procedures.
  • For patients enrolling to Part 2, prior therapy with an agent that is known or proposed to be active by action on PI3K and/or mTOR completed within the last 6 months.
  • Uncontrolled or significant cardiovascular disease:
  • A myocardial infarction within 12 months.
  • Uncontrolled angina within 6 months.
  • Congestive heart failure within 6 months.
  • Diagnosed or suspected congenital long QT syndrome.
  • Any history of ventricular arrhythmias (such as ventricular tachycardia, ventricular Fibrillation, or Torsades de pointes).
  • Any history of second or third degree heart block (may be eligible if currently have a pacemaker).
  • Heart rate <50/minute on pre entry electrocardiogram.
  • Uncontrolled hypertension.
  • Current use or anticipated need for food or drugs that are known potent CYP3A4 inhibitors. Because inhibition of CYP3A4 isoenzymes may increase PF- 05212384 exposure leading to a potential increases in toxicities, the use of known strong inhibitors (strong CYP3A4 Inhibitors: grapefruit juice or grapefruit/grapefruit related citrus fruits (eg, Seville oranges, pomelos), ketoconazole, miconazole, itraconazole, voriconazole, posaconazole, erythromycin, clarithromycin, telithromycin, verapamil, indinavir, saquinavir, ritonavir, nelfinavir, nefazodone, lopinavir, atazanavir, amprenavir, fosamprenavir and delavirdine, troleandomycin, mibefradil, conivaptan) are not permitted from 10 days prior to the first dose of study drug until discontinuation. Concurrent administration of herbal preparations and current or anticipated need for food or drugs that are known substrates of UGT1A9 (eg, propofol, acetaminophen, and propranolol), of which PF-05212384 is a strong inhibitor, is not permitted from 10 days prior to the first dose of study drug until discontinuation.
  • Current or anticipated need for food or drugs that are known potent CYP3A4 inducers. PF-05212384 metabolism may be induced when taking strong CYP3A4 inducers (eg, phenobarbital, rifampin, phenytoin, carbamazepine, rifabutin, rifapentin, clevidipine, St. John's Wort) resulting in reduced plasma concentrations. Therefore co administration of study drug in combination with these and other strong CYP3A4 inducers is not permitted from 10 days prior to the first dose of study drug until study treatment discontinuation.
  • Breast feeding or intercurrent pregnancy; no use of highly effective contraception or not agreeing to continue highly effective contraception for 90 days after last dose of investigational product.
  • Any mental disorder that would limit the understanding or rendering of informed consent and/or compromise compliance with the requirements of the protocol.

Trial locations and contacts

1 site in 1 country.

Switzerland1 site

  • Oncology Institute of Southern Switzerland (IOSI)

    Bellinzona, Canton Ticino, 6500

Other trials in Switzerland

About this study

Official title: DOSE FINDING STUDY OF PF-05212384 WITH PACLITAXEL AND CARBOPLATIN IN PATIENTS WITH ADVANCED SOLID TUMOR

This is a phase Ib single arm, open-label, multiple dose, dose escalating, safety, pharmacokinetic and pharmacodynamic study of the combination of PF-05212384 with paclitaxel and carboplatin. The study will be conducted in adult patients with advanced breast, NSCLC, ovarian or endometrial, small cell lung cancer (SCLC) and Head and Neck (HNSCC) cancer for whom there is an indication to the use of paclitaxel and carboplatin.

Successive cohorts of patients will receive escalating doses of PF-05212384 in combination with paclitaxel and carboplatin, starting at a dose level determined to be the 60% of single agent MTD.

Read more

The study will consist of two parts: the dose finding part (Part 1) and the expansion part (Part 2).

During Part 1 patients with breast, NSCLC, ovary and endometrial, small cell lung cancer (SCLC) and Head and Neck (HNSCC) cancer will be enrolled.

During Part 2, only patients with ovarian cancer will be enrolled. In Part 1, a 3+3 design is employed. Once the MTD of the combination is defined in Part 1, Part 2 is performed for a better definition of the safety profile, of the potential antitumor activity and of the pharmacodynamic effects of the combination; it will be conducted in at least 12 patients with ovarian cancer.

Approximately 40 patients are expected to be enrolled in the study overall.

Being tested
PF-05212384, Paclitaxel, Carboplatin
Keywords
Advanced solid tumor
Medical subject headings
Breast Neoplasms, Ovarian Neoplasms, Endometrial Neoplasms, Small Cell Lung Carcinoma, Squamous Cell Carcinoma of Head and Neck

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PF-05212384Drug

    iv administrartion

  • PaclitaxelDrug

    Also called Taxol

    iv administration

  • CarboplatinDrug

    Also called no applicable

    iv administration

Study groups in NCT02069158
Study groupRoleWhat they receive
PF-05212384, Carboplatin, PaclitaxelExperimentalstarting dose of PF-05212384: 95 mg iv weekly Dose of Carboplatin: 5 AUC every 28 days Dose of Paclitaxel: 80 mg/m2 on days 1, 8 and 15
Receives: Drug: PF-05212384; Drug: Paclitaxel; Drug: Carboplatin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. dose limiting toxicity (DLT)

    Assessment of the dose limiting toxicities (DLT) during first cycle

    Measured: 28 days after the first administration

  2. Adverse Events

    Adverse Event characterized by type, frequency and severity (as graded by NCICTCAE v. 4.03) during the treatment until progessive disease

    Measured: minimum 8 weeks

  3. laboratory Adverse Events

    Laboratory abnormalities characterized by type, frequency and severity (as graded by NCICTCAE v. 4.03) during all treatment until progressive disease

    Measured: minimum 8 weeks

Secondary outcomes (5)

  1. Pharmacokintecs of PF-05212384

    Evaluation of the pharmacokinetic of PF-05212384 single agent or in combination with paclitaxel and carboplatin

    Measured: Cycle 1 day 1 and Cycle 2 day 1

  2. Tumor response

    Objective tumor response assessed by Response Evaluation Criteria in Solid Tumors (RECIST), RR, TTP

    Measured: every 8 weeks

  3. biomarkers of pathway inhibition

    Serum glucose, and other circulating biomarkers of pathway inhibition (pS6K1)

    Measured: Day 1 of each cycle

  4. Pharmacodynamic

    Evaluation of the pharmacodynamic of biomarkers in tumor tissues (archived and fresh tumor biopsy)

    Measured: Just before the treatment starts and cycle 1 day 22

  5. Gene expression

    Gene expression in biopsied tumor tissues (fresh or archived) relating to PI3K and MAPK signaling

    Measured: Just before the treatment starts

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Feb 2014 (estimated)
  2. Study startApr 2014
  3. Primary completionMay 2019
  4. Study completionMay 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02069158
Sponsor's protocol ID
IOSI-NDU-001
Acronym
IOSI-NDU-001
Status last verified
May 2019
First submitted
12 Feb 2014
Last updated
21 May 2019
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing PF-05212384, Paclitaxel and Carboplatin in people with Breast Cancer and NSCLC, run by Cristiana Sessa at 1 site in Switzerland.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 May 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

dose limiting toxicity (DLT) (time frame: 28 days after the first administration). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02069158.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 May 2019.

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