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

NCT02069158 | Completed Phase 1

• 1 other identifier: IOSI-NDU-001
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief 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. 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. 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.

Conditions

Breast Cancer; NSCLC; Ovary Cancer; Endometrial Cancer; Small Cell Lung Cancer (SCLC); Head and Neck (HNSCC)

Keywords

Advanced solid tumor

Outcome Measures

Primary Outcomes (3)

• dose limiting toxicity (DLT)

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

  28 days after the first administration

• Adverse Events

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

  minimum 8 weeks

• laboratory Adverse Events

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

  minimum 8 weeks

Secondary Outcomes (5)

• Pharmacokintecs of PF-05212384

  Cycle 1 day 1 and Cycle 2 day 1

• Tumor response

  every 8 weeks

• biomarkers of pathway inhibition

  Day 1 of each cycle

• Pharmacodynamic

  Just before the treatment starts and cycle 1 day 22

• Gene expression

  Just before the treatment starts

Study Arms (1)

PF-05212384, Carboplatin, Paclitaxel

EXPERIMENTAL

starting 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

Drug: PF-05212384; Drug: Paclitaxel; Drug: Carboplatin

Interventions

PF-05212384 DRUG

iv administrartion

PF-05212384, Carboplatin, Paclitaxel

Paclitaxel DRUG

iv administration

Also known as: Taxol

PF-05212384, Carboplatin, Paclitaxel

Carboplatin DRUG

iv administration

Also known as: no applicable

PF-05212384, Carboplatin, Paclitaxel

Eligibility Criteria

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

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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).
• 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).

Sponsors & Collaborators

• Cristiana Sessa: lead

Study Sites (1)

Oncology Institute of Southern Switzerland (IOSI)

Bellinzona, Canton Ticino, 6500, Switzerland

Location

MeSH Terms

Conditions

Breast Neoplasms; Ovarian Neoplasms; Endometrial Neoplasms; Small Cell Lung Carcinoma; Squamous Cell Carcinoma of Head and Neck

Interventions

gedatolisib; Paclitaxel; Carboplatin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland 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; Uterine Neoplasms; Uterine Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms

Intervention Hierarchy (Ancestors)

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

Study Officials

• Anastasios Stathis, Prof.

  IOSI Sponsor Unit

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: February 12, 2014
• First Posted: February 24, 2014
• Study Start: April 1, 2014
• Primary Completion: May 1, 2019
• Study Completion: May 1, 2019
• Last Updated: May 21, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)