Clinical Study of Oral PI3K/mTOR Inhibitor in Patients With Advanced Refractory Solid Tumors

This study has suspended participant recruitment.
(Sponsor decision not related to patient safety)
Sponsor:
Information provided by (Responsible Party):
Piramal Enterprises Limited
ClinicalTrials.gov Identifier:
NCT01762410
First received: December 20, 2012
Last updated: September 2, 2014
Last verified: September 2014
  Purpose

Clinical study of oral PI3K/mTOR inhibitor P7170 in patients with advanced refractory solid tumors. The primary objective is to determine the maximum tolerated dose and dose limiting toxicity of oral PI3K/mTOR inhibitor P7170 in patients with advanced refractory solid tumors


Condition Intervention Phase
Advanced Refractory Solid Tumors
Drug: P7170
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label Multicentric Phase 1 Study of Oral PI3K/mTOR Inhibitor P7170 in Patients With Advanced Refractory Solid Tumors.

Resource links provided by NLM:


Further study details as provided by Piramal Enterprises Limited:

Primary Outcome Measures:
  • Maximum tolerated dose [ Time Frame: End of Cycle 1 (i.e. 21 Days) ] [ Designated as safety issue: Yes ]
    Patients will receive study drug on a daily basis for twenty-one days according to the dose and schedule specified for a particular cohort of therapy. Toxicities observed in Cycle 1 will be considered for dose limiting toxicity (DLT) and Maximum tolerated dose (MTD)determination.


Secondary Outcome Measures:
  • Number of subject with adverse events [ Time Frame: Until disease progression or unacceptable toxicity (expected to be 4-6 months) ] [ Designated as safety issue: Yes ]
    The toxic effects of the drug would be assessed from adverse events, vital signs and by clinically significant changes in the laboratory evaluations.

  • Pharmacokinetic profile(Cmax,Tmax and AUC) [ Time Frame: Until disease progression or unacceptable toxicity (expected to be 4-6 months) ] [ Designated as safety issue: No ]
    The effect of dose for AUC0-t, AUC0-inf and Cmax. Tmax and T1/2 will be given as patient-wise narratives at each dose level.

  • Activity of P7170 based on selected biomarkers [ Time Frame: Until disease progression or unacceptable toxicity (expected to be 4-6 months) ] [ Designated as safety issue: No ]
    Plasma samples will be used for analysis of exploratory biomarkers that are found in plasma and levels of which are likely to change in response to P7170 administration

  • Objective response [ Time Frame: Until disease progression or unacceptable toxicity (expected to be 4-6 months) ] [ Designated as safety issue: No ]
    Evaluation of Response: Clinical responses will be presented patient wise for different dose levels.


Estimated Enrollment: 60
Study Start Date: September 2012
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: P7170
Patients will receive study drug on a daily basis until disease progression or unacceptable toxicity in sequential cohorts following accelerated titration design.
Drug: P7170
Patients will receive study drug on a daily basis for twenty-one days according to the dose and schedule specified for a particular cohort of therapy. This 21 day administration will define a treatment cycle. Patients may receive consecutive treatment cycles until evidence of disease progression, intolerance of therapy, death or withdrawal from the protocol as specified.

Detailed Description:

An open label multicentric Phase 1 study of oral PI3K/mTOR inhibitor P7170 in patients with advanced refractory solid tumors.The study will follow an Accelerated Titration Design (ATD) with 100% dose increments until significant toxicity as described below; followed by standard dose titration with 40% dose increments. Dose and schedule (alternate dosing regimen eg. OD, BID, intermittent) will be determined by the dose escalation outlined in the protocol and considering pharmacokinetics of the study drug determined from earlier cohorts.

  Eligibility

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

Inclusion Criteria:

  • Patients having histologically and/or cytologically confirmed non-haematological malignancy that is metastatic or unresectable and for which standard curative/palliative treatment does not exist or is no longer effective or is not tolerated by patient.
  • Patients of either sex, of all races and ethnic groups, and more than 18 years of age.
  • ECOG (Eastern Cooperative Oncology Group) performance status less than 2.
  • Patients with life expectancy of at least 4 months.
  • Patients with measurable or evaluable disease per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1.
  • Patients must have adequate organ and marrow function as defined below:
  • Absolute neutrophil count more than equal to 1500/cmm
  • Platelets more than equal 100,000/cmm
  • Total bilirubin within normal limits of the institution.
  • AST/ALT less than equal 2.5 X institutional upper limit of normal (ULN) or less than equal 5 X institutional upper limit of normal (ULN) in the presence of liver metastases
  • Creatinine less than equal 1.5 X institutional upper limit of normal (ULN)
  • Women of childbearing potential and men willing to agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, during the duration of study participation and for at least 4 weeks after withdrawal from the study, unless they are surgically sterilised.
  • Ability to understand and the willingness to provide a written informed consent document.

Exclusion Criteria:

  1. Patients who have received any prior chemotherapy, radiotherapy, biologic/targeted anti-cancer therapy or surgery within 4 weeks (3 months for monoclonal antibodies, radioactive monoclonal antibodies or any radio- or toxin- immunoconjugates) before study drug administration and have not recovered (to < Grade 1) from the toxic effects from any prior therapy.
  2. Patients having received any other investigational agents within 4 weeks prior to the date of enrolment and have not recovered completely (to < Grade 1) from the side effects of the earlier investigational agent.
  3. Patients with known brain metastases (except for patients who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for two months prior to first dose of study drug.)
  4. Patients with a history of myocardial infarction or uncontrolled cardiac dysfunction during the previous 6 months.
  5. Patients with diabetes mellitus requiring insulin therapy at screening or patients with clinically significant diabetic complications, such as neuropathy, retinopathy, peripheral vascular disease or nephropathy.
  6. Clinically significant medical condition of malabsorption, inflammatory bowel disease, or chronic diarrheal condition that might affect the absorption of the investigational agent.
  7. Patients on chronic anticoagulation treatment. Prophylactic anticoagulation with low-molecular heparin is allowed.
  8. Patients with inter-current illness including, but not limited to ongoing or clinically significant active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  9. Patients with a known history of allergic reaction to any other medication considered to be clinically significant by the investigator.
  10. Women who are pregnant or nursing.
  11. Patients with immune deficiency and at increased risk of lethal infections, for example, known h/o HIV, HBV or HCV.
  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: NCT01762410

Locations
United States, California
USC Norris Comprehensive Cancer Center
Los Angeles, California, United States, 90033
India
Medanta Duke Research Institute (MDRI)
Gurgaon, Haryana, India, 122001
Central India Cancer Research Institute
Nagpur, Maharashtra, India
Meenakshi Mission Hospital & Research Centre
Madurai, Tamil Nadu, India, 625107
Sponsors and Collaborators
Piramal Enterprises Limited
Investigators
Principal Investigator: Anthony El-Khoueiry, MD University of Southern California
  More Information

No publications provided

Responsible Party: Piramal Enterprises Limited
ClinicalTrials.gov Identifier: NCT01762410     History of Changes
Other Study ID Numbers: P7170/70/11
Study First Received: December 20, 2012
Last Updated: September 2, 2014
Health Authority: United States: Food and Drug Administration
India: Drugs Controller General of India

Keywords provided by Piramal Enterprises Limited:
Advanced refractory solid tumors

Additional relevant MeSH terms:
Neoplasms
Sirolimus
Everolimus
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 22, 2014