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NCT02258659: OPTIMA

Nab-paclitaxel and Carboplatin Followed by Response-Based Local Therapy in Treating Patients With Stage III or IV HPV-Related Oropharyngeal Cancer

Completed Phase 2 Results posted Last updated 24 September 2024
What this trial tests

Phase 2 trial testing paclitaxel albumin-stabilized nanoparticle formulation in Human Papilloma Virus Infection in 62 participants. Completed in 6 September 2024.

Timeline
22 September 2014
Primary endpoint
6 September 2024
6 September 2024

Quick facts

Lead sponsorUniversity of Chicago
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment62
Start date22 September 2014
Primary completion6 September 2024
Estimated completion6 September 2024
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

University of Chicago

Who can join

18 and older, any sex, with Human Papilloma Virus Infection or Stage III Squamous Cell Carcinoma of the Oropharynx. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Progression-Free Survival (PFS), Evaluated Using RECIST Version (v) 1.1 Primary · Time from enrollment until disease progression or death from any cause, assessed at 2 years

If all patients are followed for two years, the PFS rate and confidence interval will be determined based on the exact binomial distribution. Otherwise, PFS will be estimated using the Kaplan-Meier method and a (large-sample) one-sided 90% confidence interval will be derived for the PFS rate at two years to test the non-inferiority hypothesis. Median PFS will be estimated as described in Brookmeyer and Crowley.

GroupValue95% CI
Single Arm94.588 – 96
Rate of Pathologic Complete Response (PCR) on Post Treatment Biopsy/Surgery, Evaluated Using RECIST v1.1 Secondary · Up to 8 weeks after completion of CRT

Pathologic response rates will be determined and 95% confidence intervals obtained using the exact binomial distribution.

GroupValue95% CI
Single Arm9079 – 97
Clinical Complete Response by Computerized Tomography (CT) & Magnetic Resonance Imaging (MRI) Only Secondary · Up to 5 years

Clinical response rates will be determined and 95% confidence intervals obtained using the exact binomial distribution.

complete response
GroupValue95% CI
Single Arm135.8 – 24
Partial Response
GroupValue95% CI
Single Arm8068 – 89
Stable Disease
GroupValue95% CI
Single Arm135.8 – 24
Overall Survival Secondary · From the date of registration to the date of death or date of last patient contact if censored, assessed up to 5 years

Overall survival rate

GroupValue95% CI
Single Arm8766 – 95
Cancer-specific Survival Secondary · Up to 5 years

Overall Cancer-specific survival rate. Patients dying from non-cancer related causes will be censored at the time of death.

GroupValue95% CI
Single Arm9585 – 98
Rates of Acute Toxicity, Determined by Incidence of Mucositis, Xerostomia, Anorexia, Weight Loss, Dermatitis and G-tube Placement Secondary · Up to 5 years

Toxicity rates will be summarized by type of toxicity, grade, and attribution. The incidence of acute (mucositis, xerostomia, anorexia, weight loss, dermatitis and G-tube placement) toxicities will be estimated along with 95% confidence intervals. Toxicity criteria of the Common Toxicity Criteria (CTC) and the Radiation Therapy Oncology Group (RTOG) will be used to determine grades. General CTC grade definitions: 0 = No adverse event or within normal limits; 1 = Mild adverse event; 2 = Moderate adverse event; 3 = Severe and undesirable adverse event; 4 = Life-threatening or disabling adverse e

Grade 3+ mucositis
GroupValue95% CI
Single Arm35
Grade 3+ dermatitis
GroupValue95% CI
Single Arm12
grade 3+ neutropenia
GroupValue95% CI
Single Arm29
grade 3+ Anorexia
GroupValue95% CI
Single Arm5
Rates of Late Toxicity, Determined by Incidence of Xerostomia, Dental Decay, Osteroradionecrosis, G-tube Dependency, Tracheostomy Placement and Dysphagia Secondary · Up to 5 years

Toxicity rates will be summarized by type of toxicity, grade, and attribution. The incidence of late-term (xerostomia, dental decay, osteroradionecrosis, G-tube dependency, speech abnormalities, tracheostomy placement and dysphagia) toxicities will be estimated along with 95% confidence intervals.

G-tube dependence
GroupValue95% CI
Single Arm18
Dysphagia
GroupValue95% CI
Single Arm18

Adverse events — posted to ClinicalTrials.gov

Time frame: up to 5 years. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Single Arm
Serious: 5/62 (8%)
Deaths: 5/62

Serious adverse events (10 terms)

ReactionSystemSingle Arm
FeverGeneral disorders
Abdominal painGastrointestinal disorders
AnorexiaMetabolism and nutrition disorders
AspirationRespiratory, thoracic and mediastinal disorders
ConstipationGastrointestinal disorders
DiarrheaGastrointestinal disorders
Edema limbsGeneral disorders
FatigueGeneral disorders
Neutrophil count decreasedInvestigations
Productive coughRespiratory, thoracic and mediastinal disorders
Other adverse events (56 terms — click to expand)

ReactionSystemSingle Arm
FatigueGeneral disorders
Mucositis oralGastrointestinal disorders
NauseaGastrointestinal disorders
DysgeusiaNervous system disorders
ConstipationGastrointestinal disorders
AnorexiaMetabolism and nutrition disorders
Dermatitis radiationInjury, poisoning and procedural complications
Dry mouthGastrointestinal disorders
Neutrophil count decreasedInvestigations
Platelet count decreasedInvestigations
Peripheral sensory neuropathyNervous system disorders
DiarrheaGastrointestinal disorders
Weight lossInvestigations
AnemiaBlood and lymphatic system disorders
VomitingGastrointestinal disorders
Oral painGastrointestinal disorders
FeverGeneral disorders
PainGeneral disorders
DysphagiaGastrointestinal disorders
PruritusSkin and subcutaneous tissue disorders
CoughRespiratory, thoracic and mediastinal disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
Palmar-plantar erythrodysesthesia syndromeSkin and subcutaneous tissue disorders
White blood cell decreasedInvestigations
Alanine aminotransferase increasedInvestigations
Pharyngolaryngeal painRespiratory, thoracic and mediastinal disorders
AnxietyPsychiatric disorders
Abdominal painGastrointestinal disorders
Edema limbsGeneral disorders
Esophageal painGastrointestinal disorders
InsomniaPsychiatric disorders
Aspartate aminotransferase increasedInvestigations
HeadacheNervous system disorders
LymphedemaVascular disorders
Nasal congestionRespiratory, thoracic and mediastinal disorders
Bone painMusculoskeletal and connective tissue disorders
MyalgiaMusculoskeletal and connective tissue disorders
Skin ulcerationSkin and subcutaneous tissue disorders
AlopeciaSkin and subcutaneous tissue disorders
Gastroesophageal reflux diseaseGastrointestinal disorders

Most-reported serious reactions: Fever, Abdominal pain, Anorexia, Aspiration, Constipation, Diarrhea, Edema limbs, Fatigue.

Data from ClinicalTrials.gov NCT02258659 adverse events section.

Sponsor's own description

This phase II trial studies nab-paclitaxel (paclitaxel albumin-stabilized nanoparticle formulation) and carboplatin followed by response-based local therapy in treating patients with stage III or IV human papillomavirus (HPV)-related oropharyngeal cancer. Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation, carboplatin, hydroxyurea, fluorouracil, paclitaxel, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them spreading. Radiation therapy uses high energy x rays to kill tumor cells. Giving nab-paclitaxel and carboplatin before chemoradiation may make the tumor smaller and reduce the amount of chemotherapy and radiation therapy needed. Assigning chemotherapy and radiation therapy based on response (response-based therapy) and giving patients who are responding well lower doses of treatment may help reduce the occurrence of side effects.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. OPTIMA: a phase II dose and volume de-escalation trial for human papillomavirus-positive oropharyngeal cancer.
    Seiwert TY, Foster CC, Blair EA, Karrison TG, et al · · 2019 · cited 136× · PMID 30481287 · DOI 10.1093/annonc/mdy522
  2. Treatment de-escalation for HPV-driven oropharyngeal cancer: Where do we stand?
    Mirghani H, Blanchard P. · · 2018 · cited 120× · PMID 29594236 · DOI 10.1016/j.ctro.2017.10.005
  3. Deintensification of treatment for human papillomavirus-related oropharyngeal cancer: Current state and future directions.
    Bigelow EO, Seiwert TY, Fakhry C. · · 2020 · cited 55× · PMID 32247987 · DOI 10.1016/j.oraloncology.2020.104652
  4. Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis.
    Subhan MA, Parveen F, Filipczak N, Yalamarty SSK, et al · · 2023 · cited 45× · PMID 36983571 · DOI 10.3390/jpm13030389
  5. Future trends and emerging issues for nanodelivery systems in oral and oropharyngeal cancer.
    Irimie AI, Sonea L, Jurj A, Mehterov N, et al · · 2017 · cited 32× · PMID 28721037 · DOI 10.2147/ijn.s133219
  6. Risk and response adapted de-intensified treatment for HPV-associated oropharyngeal cancer: Optima paradigm expanded experience.
    Rosenberg AJ, Agrawal N, Pearson A, Gooi Z, et al · · 2021 · cited 26× · PMID 34662771 · DOI 10.1016/j.oraloncology.2021.105566
  7. De-Escalation Strategies for Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma-Where Are We Now?
    Silver JA, Turkdogan S, Roy CF, Subramaniam T, et al · · 2022 · cited 19× · PMID 35621685 · DOI 10.3390/curroncol29050295
  8. Evolution of a Paradigm Switch in Diagnosis and Treatment of HPV-Driven Head and Neck Cancer-Striking the Balance Between Toxicity and Cure.
    Tawk B, Debus J, Abdollahi A. · · 2021 · cited 19× · PMID 35126105 · DOI 10.3389/fphar.2021.753387

Verify or expand the search:

Other trials of paclitaxel albumin-stabilized nanoparticle formulation

Trials testing the same drug.

Other recruiting trials for Human Papilloma Virus Infection

Currently open trials in the same condition.

Other University of Chicago trials

Trials by the same sponsor.

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