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Testing the Addition of Ipatasertib to Usual Chemotherapy and Radiation for Head and Neck Cancer

ConditionsClinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8Head and Neck Carcinoma of Unknown PrimaryLocally Advanced Head and Neck Squamous Cell CarcinomaLocally Advanced Hypopharyngeal Squamous Cell CarcinomaLocally Advanced Laryngeal Squamous Cell CarcinomaLocally Advanced Nasal Cavity Squamous Cell CarcinomaLocally Advanced Oral Cavity Squamous Cell CarcinomaLocally Advanced Oropharyngeal Squamous Cell CarcinomaLocally Advanced Paranasal Sinus Squamous Cell CarcinomaLocally Advanced Sinonasal Squamous Cell CarcinomaMaxillary Sinus Squamous Cell CarcinomaStage III Hypopharyngeal Carcinoma AJCC v8Stage III Laryngeal Cancer AJCC v8Stage III Lip and Oral Cavity Cancer AJCC v8Stage III Oropharyngeal (p16-Negative) Carcinoma AJCC v8Stage III Sinonasal Cancer AJCC v8Stage IVA Hypopharyngeal Carcinoma AJCC v8Stage IVA Laryngeal Cancer AJCC v8Stage IVA Lip and Oral Cavity Cancer AJCC v8Stage IVA Oropharyngeal (p16-Negative) Carcinoma AJCC v8Stage IVA Sinonasal Cancer AJCC v8Stage IVB Hypopharyngeal Carcinoma AJCC v8Stage IVB Laryngeal Cancer AJCC v8Stage IVB Lip and Oral Cavity Cancer AJCC v8Stage IVB Oropharyngeal (p16-Negative) Carcinoma AJCC v8Stage IVB Sinonasal Cancer AJCC v8
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorNational Cancer Institute (NCI)

About this trial

This phase I/Ib trial tests the safety and best dose of ipatasertib in combination with the usual treatment approach using chemotherapy together with radiation therapy ("chemo-radiation") in patients with head and neck cancer. Ipatasertib is in a class of medications called protein kinase B (AKT) inhibitors. It may stop the growth of tumor cells and may kill them. Cisplatin, which is a chemotherapy used in this trial, is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of cancer cells. Radiation therapy uses high energy to kill tumor cells and shrink tumors. Giving ipatasertib in combination with chemo-radiation may be better than chemo-radiation alone in treating patients with advanced head and neck cancer.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Patients must have pathologically confirmed HNSCC (including tumors of the oropharynx, hypopharynx, larynx, oral cavity, nasal cavity, maxillary and other paranasal sinuses, and unknown primary of the head and neck), with measurable disease as per RECIST 1.1

Oropharyngeal and unknown primary squamous cell cancers must test for human papilloma virus (HPV), for example by p16 immunohistochemistry (IHC), in situ hybridization (ISH), or polymerase chain reaction (PCR). HPV testing is not required for other HNSCC primary tumor sites

Patients with p16-positive tumors are eligible if M0 and any of one the following: cT4 or cN3 or cT2-3N2 or imaging-detected extranodal extension (iENE) according to the American Joint Committee on Cancer (AJCC)/TNM Staging System, 8th or 9th edition (Ed.)

Patients with p16-negative (or not tested) tumors are eligible if clinical stage III-IVB (locally advanced but non-metastatic) according to the AJCC/TNM Staging System, 8th or 9th Ed.

Disqualifiers

Primary tumor of nasopharynx, salivary, thyroid or parathyroid glands, or skin

Distant metastases from the current HNSCC

Prior treatment (e.g., chemotherapy, radiation, or definitive surgery) for the current locally advanced HNSCC is not permitted. Biopsies, including those performed under anesthesia, are not considered surgery. Patients who underwent prior definitive surgery alone for an early stage (T1-2N0) HNSCC which has now recurred with stage III-IVB disease at least 3 months after the initial surgery are eligible

For patients with a prior history of another malignancy, no prior chemotherapy or radiation may have been administered within 6 weeks prior to study entry. Among patients who received prior radiation to the head and neck or adjacent anatomical site for another malignancy, there may be no overlap with current area to be irradiated

Trial design

Design model

Sequential

Treatments tested in this trial

  • Biopsy Procedure

    Procedure/Surgery

    Undergo tumor biopsy

  • Biospecimen Collection

    Procedure/Surgery

    Undergo blood sample collection

  • Cisplatin

    Drug

    Given IV

  • Computed Tomography

    Procedure/Surgery

    Undergo CT or PET/CT

  • Ipatasertib

    Drug

    Given PO

  • Magnetic Resonance Imaging

    Procedure/Surgery

    Undergo MRI

  • Positron Emission Tomography

    Procedure/Surgery

    Undergo PET/CT

  • Radiation Therapy

    Radiation

    Undergo radiation therapy

Treatment groups

46 Participants
are divided into 2 treatment groups
Group A: Dose Escalation (ipatasertib, cisplatin, radiation therapy)Experimental treatment 7 interventions
Group B: Dose Expansion (ipatasertib, cisplatin, radiation therapy)Experimental treatment 8 interventions

Trial outcomes

Primary outcomes

1

Maximum tolerated dose (MTD) and recommended phase 2 dose of ipatasertib in combination with definitive chemo-radiation

Patients who receive at least 70% of the prescribed course of ipatasertib on radiation days will be evaluable for dose limiting toxicity assessment. After the escalation phase of the trial is completed, the MTD will be selected using the pooled-adjacent-violators algorithm, a type of isotonic regression, as specified in Liu and Yuan (2015).

Time frame
At the completion of dose escalation phase, up to 56 days from treatment start date

Secondary outcomes

1

Acute and late toxicities

Will be assessed according to Common Terminology Criteria for Adverse Events version 5.0. Toxicities occurring \> 90 days from the end of radiation will be considered late toxicities. This will include assessment of long-term swallowing function, based on gastric tube dependency at 6 and 12 months as compared to baseline due to the effects of the primary tumor. Descriptive statistics will be used to summarize these toxicities.

Time frame
From 90 days after the end of radiation treatment up to 1 year from treatment completion date
2

Duration and completion rate of prescribed radiation and chemotherapy

Descriptive statistics will also be used to summarize the duration and completion rate of prescribed radiation and chemotherapy.

Time frame
Up to 2 years
3

Objective response rate

Assessed based on Response Evaluation Criteria in Solid Tumors, as well as locoregional control, relapse-free survival, and overall survival. Two-sample t-test, Mann-Whitney U test, or log rank test will be used where appropriate to analyze the correlation between efficacy outcomes and pre-treatment genotypic abnormalities in the AKT pathway based on whole exome sequencing and PTEN immunohistochemistry (IHC).

Time frame
Up to 2 years
4

Pharmacokinetic (PK) profile of ipatasertib in combination with cisplatin

Will be assessed using peak and trough blood levels in patients administered ipatasertib orally during weeks 2 and 3 of study treatment. The combined therapy will be compared to historical PK data for drug alone, in order to assess for a drug-drug interaction.

Time frame
Up to 2 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

National Cancer Institute (NCI)

Lead sponsor

Source ClinicalTrials.gov
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