Study of Olaparib With Radiation Therapy and Cetuximab in Advanced Head and Neck Cancer With Heavy Smoking History

NCT01758731 | Completed Phase 1 Results DMC

• 1 other identifier: 11-1658.cc
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

This is a research study that plans to learn more about the safety and tolerability of an investigational drug called Olaparib, in combination with radiation therapy and cetuximab. Hypothesis: Intensity modulated radiotherapy with concurrent C225 and Olaparib represents a feasible, biologically-based alternative to standard chemoradiation, with acceptable toxicity, for treatment of locally-advanced HNSCC in patients having a ≥ 10 pack-year smoking history.

Conditions

Squamous Cell Carcinoma of the Head and Neck

Keywords

Stage IVA-B Squamous Cell Carcinomas; Head and Neck Cancer; Heavy drinking; Smoking

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of Olaparib

  Maximum tolerated dose (MTD) of Olaparib to be used for Phase II clinical testing.

  10 weeks from the start of protocol therapy

Study Arms (1)

Olaparib with C225 and Radiation Therapy

EXPERIMENTAL

Patients will begin taking Olaparib at the assigned dose three days prior to their first Cetuximab infusion. Patients will receive an initial dose of Cetuximab, 400 mg/m², intravenously over 120 minutes on Day 1. The initial dose of C225 will precede the start of radiation by 5-7 days. All patients will receive RT to a total dose of 69.3 Gy in 33 fractions over 6½ weeks. Weekly C225 will be administered at 250 mg/m2 in combination with daily RT. Patients will be assigned to receive Olaparib (25, 50, 100 or 200 mg bid) in combination with RT and C225. Olaparib will be taken twice daily, beginning three days prior to first scheduled C225 infusion. A further dose level of 300mg or 400mg may be considered should the 200mg Olaparib dose be well tolerated in this C225/RT combination schedule.

Drug: Olaparib; Drug: Cetuximab; Radiation: Radiation Therapy

Interventions

Olaparib DRUG

Olaparib PO (25, 50, 100 or 200 mg bid) in combination with RT and C225. BID, beginning three days prior to first C225 infusion and discontinued after RT completed.

Also known as: AZD2281

Olaparib with C225 and Radiation Therapy

Cetuximab DRUG

Pre-RT cetuximab (C225), 400 mg/m²IV and weekly C225, 250 mg/m2 IV in during RT.

Also known as: Erbitux

Olaparib with C225 and Radiation Therapy

Radiation Therapy RADIATION

RT to a total dose of 69.3 Gy (primary tumor and involved lymph nodes) in 33 fractions over 6 and 1/2 weeks

Olaparib with C225 and Radiation Therapy

Eligibility Criteria

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

You may qualify if:

• Provision of fully informed consent prior to any study specific procedures.
• Patients must be \> 18 years of age.
• Histologically or cytologically confirmed (from the primary lesion and/or regional lymph nodes) squamous cell carcinoma of the oropharynx, hypopharynx, or larynx that has not been previously treated or resected
• Stage IV A or stage IV B disease prior to induction chemotherapy with no proven hematogenous metastatic disease (includes T4aN0-1M0, T1-4aN2M0, T4b, any N, M0 or any T, N3M0)
• History of ≥ 10 pack-years of smoking cigarettes.
• Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:
• Hemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• White blood cells (WBC) \> 3x109/L
• Platelet count ≥ 100 x 109/L
• Total bilirubin ≤ 1.5 x institutional upper limit of normal
• Aspartate Aminotransferase(AST) (SGOT)/Alanine Aminotransferase (ALT) (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present in which case it must be ≤ 5x ULN
• Serum creatinine ≤ 1.5 x institutional upper limit of normal (ULN)
• Creatinine clearance (CCr) ≥ 50 ml/min within 2 weeks prior to registration as determined by 24-hour collection or estimated by Cockcroft-Gault formula:
• CCr male = \[(140 - age) x (wt in kg)\]/ \[(Serum Cr mg/dl) x (72)\] CCr female = 0.85 x (CrCl male)

You may not qualify if:

• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
• Previous enrollment (or assignment) in the present study
• Treatment with any investigational product during the last 14 days (or a longer period depending on the defined characteristics of the agents used)
• Any previous treatment with a PARP inhibitor, including olaparib.
• Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for ≥ 5 years.
• Patients receiving any systemic chemotherapy or targeted agents for treatment of the current HNSCC
• Patients receiving any prior radiation therapy to the head or neck.
• Patients receiving the following classes of inhibitors of Cytochrome P450 3A4 (see Section 5.4.2 for guidelines and wash out periods).
• Azole antifungals
• Macrolide antibiotics
• Protease inhibitors
• Toxicities \> Common Toxicity Criteria for Adverse Effects (CTCAE) grade 2 caused by previous cancer therapy.
• Patients with metastatic disease (only Stage IVA-B patients permitted)
• Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.
• Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent. Evidence of severe or uncontrolled systemic disease or any concurrent condition which, in the investigator's opinion, makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol.

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

University of Colorado Denver

Denver, Colorado, 80045, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Smoking

Interventions

olaparib; Cetuximab; Radiotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Behavior

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Therapeutics

Limitations and Caveats

Tablets not crushable when patients were having difficulty swallowing; adaptive radiotherapy along with skin sparing wasn't formally incorporated into trial which might have led to less skin toxicity with cetuximab combined with olaparib

Results Point of Contact

• Title: Dr. David Raben
• Organization: University of Colorado, Denver

david.raben@ucdenver.edu

303-724-3027

Study Officials

• David Raben, M.D

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: December 26, 2012
• First Posted: January 1, 2013
• Study Start: October 22, 2012
• Primary Completion: December 5, 2016
• Study Completion: October 31, 2018
• Last Updated: September 23, 2019
• Results First Posted: September 23, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)