Safety and Efficacy Study of P276-00 in Combination With Radiation in Subjects With Advanced Head and Neck Cancer (SPARK)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Piramal Enterprises Limited
ClinicalTrials.gov Identifier:
NCT00899054
First received: May 6, 2009
Last updated: November 21, 2012
Last verified: November 2012
  Purpose

The purpose of this study is to identify a dose of P276-00 that can be safely administered along with Radiation and to examine safety and efficacy of the combination in treatment of advanced head and neck cancer.


Condition Intervention Phase
Squamous Cell Carcinoma of Head and Neck
Drug: P276-00
Radiation: External beam radiotherapy (EBRT)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label, Multicenter Phase I/II Study Of Selective Cyclin Dependent Kinase Inhibitor P276-00 In Combination With Radiation In Subjects With Recurrent And/Or Locally Advanced Squamous Cell Carcinoma Of Head And Neck

Resource links provided by NLM:


Further study details as provided by Piramal Enterprises Limited:

Primary Outcome Measures:
  • To determine the maximum tolerated dose (MTD) and dose limiting toxicity (ies) (DLT/s) of P276-00 in combination with radiation in subjects with recurrent and/or locally advanced squamous cell carcinoma of head and neck (SCCHN) [ Time Frame: 3 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To evaluate safety and tolerability of the combination regimen of P276-00 and radiation in the study population [ Time Frame: Every week ] [ Designated as safety issue: Yes ]
  • To analyze pharmacokinetics (PK) of P276-00 in the study population [ Time Frame: Day 2 and Day 5 of Cycle 1 ] [ Designated as safety issue: No ]
  • To evaluate efficacy of the combination regimen of P276-00 and radiation in the study population [ Time Frame: Every 6 weeks ] [ Designated as safety issue: No ]
  • To perform exploratory analysis of biomarkers associated with use of P276-00 and radiation in the study population [ Time Frame: Day 1 and Day 4 ] [ Designated as safety issue: No ]

Enrollment: 23
Study Start Date: August 2009
Study Completion Date: November 2012
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: P276-00 plus Radiation

P276-00:

Level 1:100 mg/m2/day x 5 q 3 weeks, level 2:140 mg/m2/day x 5 q 3 weeks, level 3: 185 mg/m2/day x 5 q 3 weeks.

External beam radiotherapy (EBRT):

2 Gy per day for 5 days a week for a total radiation dose of 60 Gy over 2 cycles (6 weeks)followed by upto 10 additional Gy if required

Drug: P276-00
P276-00 will be administered at different dose levels: level 1: 100 mg/m2/day dose level 2: 140 mg/m2/day dose level 3: 185 mg/m2/day to be given from day 1 to day 5 every 21 days for 2 cycle. P276-00 will be administered as intravenous infusion in 200 ml 5% Dextrose over 30 min from days 1 to 5 per 21 day cycle for two cycles.
Other Name: P276-00
Radiation: External beam radiotherapy (EBRT)
All subjects will receive external beam radiotherapy (EBRT)by using standard conventional fractionation i.e. 2 Gy per day for 5 days a week for a total radiation dose of 60 Gy over 6 weeks followed by upto 10 additional Gy if required.
Other Name: Radiotherapy

Detailed Description:

This is an open label single arm multicenter trial to evaluate safety and efficacy of P276-00 in combination with radiation in patients with recurrent and/or locally advanced squamous cell carcinoma of head and neck. The Primary objective of this study is to determine maximum tolerated dose (MTD) and dose limiting toxicity (ies) (DLT/s) of P276-00 in combination with radiation in subjects with recurrent and/or locally advanced squamous cell carcinoma of head and neck (SCCHN). The Secondary objectives are 1. To evaluate safety and tolerability of the combination regimen of P276-00 and radiation in the study population 2. To analyze pharmacokinetics (PK) of P276-00 in the study population 3. To evaluate efficacy of the combination regimen of P276-00 and radiation in the study population 4. To perform exploratory analysis of biomarkers associated with use of P276-00 and radiation in the study population. In phase 1 component,a cohort of 3 subjects will be enrolled at starting dose level of P276-00 which is 100 mg/m2/day to be given intravenously from day 1 to day 5 in 21 day cycle for 2 cycles in combination with radiation. If this dose is well tolerated then next cohort will be enrolled at higher dose level of P276-00. P276-00 dose escalation will continue until MTD of P276-00 in combination with Radiation is determined. The subsequent dose levels of P276-00 will be 140 mg/m2/day and 185 mg/m2/day.

In phase 2 component 10 subjects will be enrolled at this MTD of P276-00 in combination with radiation to evaluate efficacy. Dose of radiation for both phases is 60 Gy over 6 weeks. Safety evaluations will be conducted at regular intervals during the study. Tumor measurements will be undertaken at baseline, at the end of cycle 2 and 5 to 6 weeks after end of cycle 2. Response evaluation will be performed by Response Evaluation Criteria in Solid Tumors (RECIST). Subjects showing stable disease or better response at the last assessment will be followed up for tumor measurements until progression or recurrence of disease.

  Eligibility

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

Inclusion Criteria:

  1. Disease specifications:

    • Phase I component: Radiation naïve subjects with histologically and/ or cytologically confirmed squamous cell carcinoma of head and neck that is non-metastatic, unresectable and recurrent. Radiation naïve subjects with non-recurrent, non-metastatic, unresectable, disease can also be enrolled if he/she is intolerant to and/or unwilling for chemoradiotherapy involving standard cytotoxic agents (e.g. cisplatin, carboplatin, oxaliplatin, 5-FU, taxanes, methotrexate, etc)
    • Phase II component: Radiation naïve subjects with non-recurrent, non-metastatic, unresectable, locally advanced squamous cell carcinoma of head and neck who are intolerant to and/or unwilling for chemoradiotherapy involving standard cytotoxic agents (e.g. cisplatin, carboplatin, oxaliplatin, 5-FU, taxanes, methotrexate, etc).
  2. Treatment specifications:

    • Phase I Component: subjects must not have received any treatment (chemotherapy, targeted or biologic agents, radiotherapy, surgery etc) for the recurrent disease.
    • Phase II Component: The subjects must not have been curatively operated for the disease.
  3. Subjects must have completed any prior chemotherapy, biologic/targeted anti-cancer therapy or surgery at least 4 weeks (at least 6 weeks for nitrosureas and mitomycin C) before initiation of protocol treatment and subjects must have recovered (to < or = grade 1) from the toxic effects from any prior therapy
  4. Measurable disease as per RECIST criteria.
  5. Age > or = 18 years
  6. ECOG (Eastern Cooperative Oncology Group) performance status < or = 2
  7. Life expectancy of at least 12 weeks
  8. Normal organ and marrow function:

    • Hemoglobin > or = 100 g/L
    • Leukocytes > or = 3 x 109/L
    • Absolute Neutrophil Count (ANC)> or = 1.5 x 109/L
    • Platelets > or = 75 x 109/L
    • Total bilirubin < or = 1.5 X institutional Upper Limit of Normal (ULN)
    • AST(SGOT)< or = 2.5 X institutional ULN
    • ALT(SGPT)< or = 2.5 X institutional ULN
    • Creatinine < or = 1.5 X institutional ULN
  9. Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

  1. Nasopharyngeal carcinoma
  2. Subjects who had received any other investigational drug within 1 month prior to day 1 of study drug administration or who have not recovered (to < or = grade 1) from adverse effects of the investigational agent received prior to this period.
  3. History of unstable angina or myocardial infarction or stroke within 6 months prior to initiation of protocol treatment.
  4. QTcF > 450 msec
  5. Subjects with uncontrolled inter-current illness including, but not limited to active infection, symptomatic congestive heart failure, cardiac arrhythmia, psychiatric illness or any condition that would limit compliance with study requirements.
  6. Subjects known to be suffering from infection with HIV, Tuberculosis, Hepatitis C or Hepatitis B.
  7. Women who are pregnant or lactating.
  8. Women of childbearing potential [defined as a sexually mature woman who has not undergone hysterectomy or who has not been naturally postmenopausal for at least 24 consecutive months (i.e. who has had menses any time in the preceding 24 consecutive months)] and men, not agreeing to use at least two approved methods of contraception, including at least one barrier method prior to study entry (after signing the informed consent document), during the duration of study participation and for at least 4 weeks after withdrawal from the study drug, unless they are surgically sterilised.
  9. Any condition, including laboratory abnormalities, that in the opinion of the investigator places the subject at an unacceptable risk or deems the subject not suitable for participation in the 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: NCT00899054

Locations
India
Government Medical College
Aurangabad, Maharashtra, India, 431001
Curie Manavata Cancer Center
Nashik, Maharashtra, India, 422 004
Bhagwan Mahawir Cancer Hospital & Research Centre
Jaipur, Rajasthan, India, 302017
V. N. Cancer Centre, GKNM Hospital
Coimbatore, Tamil Nadu, India, 641037
Meenakshi Mission Hospital & Research Centre
Madurai, Tamil Nadu, India, 625107
Christian Medical College
Vellore, Tamil Nadu, India, 632 004
Sponsors and Collaborators
Piramal Enterprises Limited
Investigators
Principal Investigator: Kirushna Kumar, MD, RT Meenakshi Mission Hospital & Research Centre, Madurai, India
Principal Investigator: Raj Nagarkar, MS Curie Manavata Cancer Center, Nashik, India
Principal Investigator: Subhashini John, MD , DMRT Christian Medical College, Vellore, India
Principal Investigator: Balaji Shewalkar, MD, DNB Government Medical College, Aurangabad, India
Principal Investigator: M. Nagarajan, MD, DNB V. N. Cancer Centre, GKNM Hospital, Coimbatore, India
Principal Investigator: Naresh Somani, DM Bhagwan Mahawir Cancer Hospital & Research Centre, Jaipur, India
  More Information

No publications provided

Responsible Party: Piramal Enterprises Limited
ClinicalTrials.gov Identifier: NCT00899054     History of Changes
Other Study ID Numbers: P276-00/31/08, P276-00/31/08
Study First Received: May 6, 2009
Last Updated: November 21, 2012
Health Authority: India: Drugs Controller General of India

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell
Cyclin-Dependent Kinase Inhibitor Proteins
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on October 20, 2014